The current study aims to find the role of Enhance Recovery Pathway (ERP) as a multidisciplinary approach aimed to expedite rapid recovery, reduce LOS, and minimize morbidity associated with Non Fusion Anterior Scoliosis Correction (NFASC) surgery.

A retrospective analysis of 35 AIS patients who underwent NFASC with Lenke 1 and Lenke 5 curves with a minimum of 1 year of follow-up was done. Patient demographics, surgical details, postoperative analgesia, mobilization, length of stay (LOS), patient satisfaction survey score with respect to information and care, and 90 days complications were collected.

The cohort included 34 females and 1 male with a mean age of 15.2 years at the time of surgery. There were 16 Lenke 1 and 19 Lenke 5 in the study. Mean preoperative major thoracic and thoracolumbar/lumbar Cobb's angle were 52˚±7.6˚ and 51˚±4.5˚ respectively. Average blood loss and surgical time were 102 ±6.4 ml and 168 ± 10.2 mins respectively. Average time to commencing solid food was 6.5±1.5 hrs. Average time to mobilization following surgery was 15.5± 4.3 hrs. The average duration to the stopping of the epidural was 42.5±3.5 hrs. The average dose of opioid consumption intraoperatively was 600.5±100.5 mcg of fentanyl i.v. and 12.5±4.5 mg morphine i.v. Postoperatively opioids were administered via an epidural catheter at a dose of 2 mg of morphine every 24 hours up to 2 days and an infusion of 2mcg/hr of fentanyl along with 0.12-0.15% ropivacaine. The average duration to transition to oral analgesia was 55.5±8.5 hrs .20 patients had urinary catheter and the average time to removal of the catheter was 17.5±1.4 hrs. 25 patients had a chest tube and the average time to remove of chest tube was 25.5±3.2 hrs. The average length of hospital stay was 3.1±0.5 days. No patient had postoperative ileus or requirement of blood transfusion or any other complications. No correlation was found between LOS and initial cobb angle.

The application of ERP in AIS patients undergoing NFASC results in reduced LOS and indirectly the cost, reduced post-operative opioid use, and overall improve patient satisfaction score.

The aim of this study was to perform a systematic review of the literature on Gustilo-Anderson (GA) type IIIB open tibial shaft (AO-42) injuries to determine the consistency of reporting in the literature.

A search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials was performed to identify relevant studies published from January 2000 to January 2021 using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The study was registered using the PROSPERO International prospective register of systematic reviews. Patient/injury demographics, management and outcome reporting were recorded.

There were 32 studies that met the inclusion criteria with a total of 1,947 patients (70.3% male, 29.7% female). There were 6 studies (18.8%) studies that reported on comorbidities and smoking, with mechanism of injury reported in 22 (68.8%). No studies reported on all operative criteria included, with only three studies (9.4%) reporting for time to antibiotics, 14 studies (43.8%) for time from injury to debridement and nine studies (28.1%) for time to definitive fixation. All studies reported on the rate of deep infection, with a high proportion documenting union rate (26/32, 81.3%). However, only two studies reported on mortality or on other post-operative complications (2/32, 6.3%). Only 12 studies (37.5%) provided any patient reported outcomes.

This study has demonstrated a deficiency and a lack of standardized variable and outcome reporting in the orthopaedic literature for Gustilo-Anderson type IIIB open tibial shaft fractures. We propose a future international collaborative Delphi process is needed to standardize.

The purpose of this study is to report the clinical and radiological outcomes of patients undergoing primary or revision reverse total shoulder arthroplasty using custom 3D printed components to manage severe glenoid bone loss with a minimum of 2-year follow-up.

After ethical approval (reference: 17/YH/0318), patients were identified and invited to participate in this observational study. Inclusion criteria included: 1) severe glenoid bone loss necessitating the need for custom implants; 2) patients with definitive glenoid and humeral components implanted more than 2 years prior; 3) ability to comply with patient reported outcome questionnaires. After seeking consent, included patients underwent clinical assessment utilising the Oxford Shoulder Score (OSS), Constant-Murley score, American Shoulder and Elbow Society Score (ASES), and quick Disabilities of the Arm, Shoulder, and Hand Score (quickDASH). Radiographic assessment included AP and axial projections. Patients were invited to attend a CT scan to confirm osseointegration. Statistical analysis utilised included descriptive statistics (mean and standard deviation) and paired t test for parametric data.

3 patients had revision surgery prior to the 2-year follow-up. Of these, 2/3 retained their custom glenoid components. 4 patients declined to participate. 5 patients were deceased at the time of commencement of the study. 21 patients were included in this analysis. The mean follow-up was 36.1 months from surgery (range 22–60.2 months). OSS improved from a mean 16 (SD 9.1) to 36 (SD 11.5) (p < 0.001). Constant-Murley score improved from mean 9 (SD 9.2) to 50 (SD 16.4) (p < 0.001). QuickDASH improved from mean 67 (SD 24) to 26 (SD 27.2) (p = 0.004). ASES improved from mean 28 (SD 24.8) to 70 (SD 23.9) (p = 0.007). Radiographic evaluation demonstrated good osseointegration in all 21 included patients.

The utility of custom 3D-printed components for managing severe glenoid bone loss in primary and revision reverse total shoulder arthroplasty yields significant clinical improvements in this complex patient cohort.

Screw fixation is an established method for anterior cruciate ligament (ACL) reconstruction, although with a high rate of implant-related complications. An allograft system for implant fixation in ACL reconstruction, the Shark Screw ACL (surgebright GmbH) could overcome some of the shortcomings of bioabsorbable screws, such as foreign body reaction, need for implant removal and imaging artefacts. However, it needs to provide sufficient mechanical stability. Therefore, the aim of this study was to investigate the biomechanical stability, especially graft slippage, of the novel allograft system versus a conventional bioabsorbable interference screw (BioComposite Interference Screw; Arthrex Inc.) for tibial implant fixation in ACL reconstruction.

Twenty-four paired human proximal tibiae (3 female, 9 male, 72.7 ± 5.6 years) underwent ACL reconstruction. The quadrupled semitendinosus and gracilis tendon graft were fixed in one specimen of each pair using the allograft fixation system Shak Screw ACL and the contralateral one using an interference screw. All specimens were cyclically loaded at 1 Hz with peak load levels monotonically increased from 50 N at a rate of 0.1 N/cycle until catastrophic failure. Relative movements of the graft versus the tibia were captured with a stereographic optical motion tracking system (Aramis SRX; GOM GmbH).

The two fixation methods did not demonstrate any statistical difference in ultimate load at graft slippage (p = 0.24) or estimated survival at slippage (p = 0.06). Both, the ultimate load and estimated survival until failure were higher in the interference screw (p = 0.04, and p = 0.018, respectively). Graft displacement at ultimate load reached values of up to 7.2 mm (interference screw) and 11.3 mm (Shark Screw ACL).

The allograft screw for implant fixation in ACL reconstruction showed similar behavior in terms of graft slippage compared to the conventional metal interference screw but underperformed in terms of ultimate load. However, the ultimate load may not be considered a direct indicator of clinical failure.

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remain a challenge. A novel surgical technique named Tibial Cortex Transverse Transport has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In present study, we aimed to explore the wound healing effects after undergoing this novel technique via multiple ways.

A novel rat model of Tibial Cortex Transverse Transport was established with a designed external fixator and effects on wound healing were investigated. All rats were randomized into 3 groups, with 12 rats per group: sham group (negative control), fixator group (positive control) and Tibial Cortex Transverse Transport group. Laser speckle perfusion imaging, vessel perfusion, histology and immunohistochemistry were used to evaluate the wound healing processes.

Gross and histological examinations showed that Tibial Cortex Transverse Transport technique accelerated wound closure and enhanced the quality of the newly formed skin tissues. In Tibial Cortex Transverse Transport group, HE staining demonstrated a better epidermis and dermis recovery, while immune-histochemical staining showed that Tibial Cortex Transverse Transport technique promoted local collagen deposition. Tibial Cortex Transverse Transport technique also benefited to angiogenesis and immunomodulation. In Tibial Cortex Transverse Transport group, blood flow in the wound area was higher than that ofother groups according to laser speckle imaging with more blood vessels observed. Enhanced neovascularization was seen in the Tibial Cortex Transverse Transport group with double immune-labelling of CD31 and α-SMA. The M2 macrophages at the wound site in the Tibial Cortex Transverse Transport group was also increased.

Tibial cortex transverse transport technique accelerated wound healing through enhanced angiogenesis and immunomodulation.

Stem cells are known to have low levels of intracellular reactive oxygen species (ROS) and high levels of glutathione. ROS are thought to interact with several pathways that affect the transcription machinery required for stem cell differentiation, and are critical for maintaining stem cell function. In this study, we are developing a new fluorescent probe that rapidly and reversibly reacts with glutathione (GSH), the most abundant non-protein thiol in living cells that acts as an antioxidant and redox regulator.

Multipotent perivascular progenitor cells derived from human ESCs (hESC-PVPCs): Differentiated ESCs as embryoid bodies in the presence of BMP4 to induce mesoderm differentiation followed by a simple cell selection strategy using attachment of single cells onto collagen-coated dishes. Differential gene expression profiling was performed among H9 hESCs, EBs induced by BMP4 and naturally selected CD140B+CD44+ population at Day 7 (PVPCs). Colony-forming assay: GSHhigh and GSHlow PVPCs were plated on 10-cm tissue culture-treated polystyrene dishes in triplicate in growth medium and cultured for 14 days. Transwell migration assay: GSHhigh and GSHlow PVPCs at passage 4 were resuspended at 1 × 10⁶/mL in the migration medium and seeded in the upper chamber. The following human recombinant SDF-1 and PDGF-AA proteins were used as chemoattractants in the lower compartment.

Probe-GSH conjugate shows shifts in fluorescence excitation and emission spectra that enables ratiometric measurement of GSH levels. Using these properties, stem cells can be purified by FACS-based technology according to intracellular GSH level. We are developing a protocol both for comparing GSH level in stem cell from different culture conditions and for preparing stem cells with high-GSH level . Our results reveal that GSHhigh PVPC purified by FACS show increased colony forming ability compared with that GSHlow PVPC, indicating that intracellular GSH contributes to the maintenance of stemness. Moreover, transplantation of GSHlow PVPC is more effective than that of GSHlow PVPC for cartilage regeneration in osteochondral defect.

This technique enable FACS-based sorting of stem cells according to intracellular GSH levels and thus investigation of functional role of GSH (high antioxidant capacity) in the stem cell maintenance and chondrogenic differentiation.

TGF-β/Smad2 signaling is considered to be one of the important pathways involved in osteoarthritis (OA) and protein phosphatase magnesium-dependent 1A (PPM1A) functions as an exclusive phosphatase of Smad2 and regulates TGF-β signaling, here, we investigated the functional role of PPM1A in OA pathogenesis.

PPM1A expressions in both human OA cartilage and experimental OA mice chondrocytes were analyzed immunohistochemically. Besides, the mRNA and protein expression of PPM1A induced by IL-1β treatment were also detected by q-PCR and immunofluorescence in vitro. OA was induced in PPM1A knockout (KO) mice by destabilization of the medial meniscus (DMM), and histopathological examination was performed. OA was also induced in wild-type (WT) mice, which were then treated with an intra-articular injection of a selective PPM1A inhibitor for 8 weeks.

PPM1A protein expressions were increased in both human OA cartilage and experimental OA mice chondrocytes. We also found that treatment with IL-1β in mouse primary chondrocytes significantly increased both mRNA and protein expression of PPM1A in vitro. Importantly, our data showed that PPM1A deletion could substantially protect against surgically induced OA. Concretely, the average OARSI score and quantification of BV/TV of subchondral bone in KO mice were significantly lower than that in WT mice 8 weeks after DMM surgery. Besides, TUNEL staining revealed a significant decrease in apoptotic chondrocytes in PPM1A-KO mice with DMM operation. With OA induction, the rates of chondrocytes positive for Mmp-13 and Adamts-5 in KO mice were also significantly lower than those in WT mice. Moreover, compared with WT mice, the phosphorylation of Smad2 in chondrocytes was increased in KO mice underwent DMM surgery. However, articular-injection with SD-208, a selective inhibitor of TGF-β/Smad2 signaling could significantly abolish the chondroprotective phenotypes in PPM1A-KO mice. Additionally, both cartilage degeneration and subchondral bone subchondral bone sclerosis in DMM model were blunted following intra-articular injection with BC-21, a small-molecule inhibitor for PPM1A.

Our study demonstrated that PPM1A inhibition attenuates OA by regulating TGF-β/Smad2 signaling. Furthermore, PPM1A is a potential target for OA treatment and BC-21 may be employed as alternative therapeutic agents for the management of OA.

This study aimed to quantify self-reported outcomes and walking gait biomechanics in patients following primary and revision THA. The specific goals of this study were to investigate: (i) if primary and revision THA patients have comparable preoperative outcomes; and (2) if revision THA patients have worse postoperative outcomes than primary THA patients.

Forty-three patients undergoing primary THA for osteoarthritis and 23 patients undergoing revision THA were recruited and followed longitudinally for their first 12 postoperative months. Reasons for revision were loosening (73%), dislocation (9%), and infection (18%). Patients completed the Hip dysfunction and Osteoarthritis Outcome Score (HOOS), and underwent gait analysis preoperatively, and at 3 and 12 months postoperatively. A 10 camera motion analysis system (V5 Vantage, Vicon, UK) recorded marker trajectories (100 Hz) during walking at self- selected speeds. A generic lower-body musculoskeletal model (Gait2392) was scaled using principal component analysis [1] and the inverse kinematics tool in Opensim 3.3 was used to compute joint angles for the lower limbs in the sagittal plane. Independent samples t-test were used to compare patient reported outcomes between the primary and revision groups at each timepoint. Statistical parametric mapping was used to compare gait patterns between the two groups at each timepoint.

Preoperatively, patients undergoing primary THA reported significantly worse pain (p<0.001), symptoms (p<0.001), function (p<0.001), and quality of life (p=0.004). No differences were observed at 3 and 12 months postoperatively between patients who had received a primary or revision THA. The only observed difference in gait pattern was that patients with a revision THA had reduced hip extension at 3 months, but no differences were observed preoperatively and 12 months.

Despite the suggestions in the literature that revision THA is bound to have worse outcomes compared to primary THA, we found no differences in in patient-reported outcomes and gait patterns at 12 months postoperatively. This suggests that it may be possible, in some circumstances, for patients following revision THA to achieve similar outcomes to their peers undergoing primary THA.

Many factors have been reported to affect the functional survival of OCA transplants, including chondrocyte viability at time of transplantation, rate and extent of allograft bone integration, transplantation techniques, and postoperative rehabilitation protocols and adherence. The objective of this study was to determine the optimal subchondral bone drilling technique by evaluating the effects of hole diameter on the material properties of OCAs while also considering total surface area for potential biologic benefits for cell and vascular ingrowth.

Using allograft tissues that would be otherwise discarded in combination with deidentified diagnostic imaging (MRI and CT), a model of a large shell osteochondral allograft was recreated using LS-PrePost and FEBio based on clinically relevant elastic material properties for cortical bone, trabecular bone, cartilage, and hole ingrowth tissue. The 0.8 mesh size model consisted of 4 mm trabecular bone, 4 mm cortical bone, and 3 mm cartilage sections that summed to a cross-sectional area of 1600 mm2 (40 mm x 40 mm). Holes were modeled to be 4mm deep in relation to clinical practice where holes are drilled from the deep margin of subchondral trabecular bone to the cortical subchondral bone plate. To test the biomechanic variations between drill hole sizes, models with hole sizes pertinent to standard-of-care commercially available orthopaedic drill sizes of 1.1mm, 2.4 mm, or 4.0 mm holes were loaded across the top surface over a one second duration and evaluated for effective stress, effective strain, 1st principal strain, and 3rd principal strain in compressive conditions.

Results measured effective stress and strain and 1st and 3rd principal strain increased with hole depth.

The results of the present FEA modeling study indicate that the larger 4.0 mm diameter holes were associated with greater stresses and strains within OCA shell graft, which may render the allograft at higher risk for mechanical failure. Based on these initial results, the smaller diameter 2.4 mm and 1.1 mm holes will be further investigated to determine optimal number, configuration, and depth of subchondral drilling for OCA preparation for transplantation

Despite the growing success of OCA transplantation in treating large articular cartilage lesions in multiple joints, revisions and failures still occur. While preimplantation subchondral drilling is intended to directly decrease allograft bioburden and has been associated with significant improvements in outcomes after OCA transplantation, the effects of size, number, and spacing of subchondral bone drill sites have not been fully evaluated. This study aimed to investigate the effects of drill size with or without pulse-lavage of OCA subchondral bone by quantifying remnant marrow elements using histomorphometry.

With IRB and ACUC approvals, human and canine OCAs were acquired for research purposes. Portions of human tibial plateau OCAs acquired from AATB-certified tissue banks that would otherwise be discarded were recovered and sectioned into lateral and medial hemiplateaus (n=2 each) with a thickness of 7 mm. Canine femoral condyles and tibial plateaus were split into lateral and medial components with a thickness of 7 mm (n=8). Using our clinical preimplantation preparation protocol, holes were drilled into the subchondral bone of each condyle and hemiplateau OCA using either 1.6 mm OD or 3.2 mm OD drill bits from the cut surface to the cortical subchondral bone plate. One femoral condyle and one hemiplateau per drill bit size were pulse-lavaged while the corresponding OCAs were not. The mean total %-fill remaining marrow elements for each treatment group was calculated.

Little to no quantifiable bone marrow element retention was noted to remain within the subchondral bone of human or canine OCA specimens after subchondral drilling of allograft bone with either drill bit size evaluated and with or without pulse-lavage. The %-fill was consistent across zones, ranging from 1-5%.

This project was designed to provide a preliminary histologic evaluation of the effects of drill size on OCA preimplantation preparation efficacy based on amount of remaining bone marrow elements in human and canine femoral condyle and tibial plateau specimens. Based on these initial findings, choice of drill bit size for OCA subchondral drilling may need to be based on the associated biomechanical effects rather than effects on donor bone marrow element removal.

Knee pain is common, representing a significant socioeconomic burden. Caused by a variety of pathologies, its evaluation in primary-care is challenging. Subsequently, an over-reliance on magnetic resonance imaging (MRI) exists. Prior to orthopaedic surgeon referral, many patients receive no, or incorrect, imaging. Electronic-triage (e-triage) tools represent an innovative solution to address this problem. The primary aim of this study was to ascertain whether an e-triage tool is capable of outperforming existing clinical pathways to determine the correct pre-hospital imaging based on knee pain diagnosis.

Patients ≥18 years with a new presentation of knee pain were retrospectively identified. The timing and appropriateness of imaging was assessed. A symptom-based e-triage tool was developed, using the Amazon LEXbotplatform, and piloted to predict five common knee pathologies and suggest appropriate imaging.

1462 patients were identified. 17% of arthroplasty patients received an ‘unnecessary MRI’, whilst 28% of arthroscopy patients did not have a ‘necessary MRI’, thus requiring a follow-up appointment, with a mean delay of three months (SD 2.6, range 0.2-20.2). Using NHS tariffs, a wasted cost through unnecessary/necessary MRIs and subsequent follow-up appointments was estimated at £45,816. The e-triage pilot was trialled with 41 patients (mean age:58.4 years, 58.5% female). Preliminary diagnoses were available for 34 patients. Using the highest proportion of reported symptoms in the corresponding group, the e-triage tool correctly identified three of the four knee pathologies. The e-triage tool did not correctly identify anterior cruciate ligament injuries (n=3). 79.2% of participants would use the tool again.

A significant number of knee pathology patients received incorrect imaging prior to their initial hospital appointment, incurring delays and unnecessary costs. A symptom-based e-triage tool was developed, with promising pilot data and user feedback. With refinement, this tool has the potential to improve wait-times and referral quality, whilst reducing costs.

Quantitative ultrasound (QUS) is a promising tool to estimate bone structure characteristics and predict fragile fracture. The aim of this pilot cross-sectional study was to evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragile fractures retrospectively in postmenopausal women.

Intraneural electrodes can be harnessed to control neural prosthetic devices in human amputees. However, in chronic implants we witness a gradual loss of device functionality and electrode isolation due to a nonspecific inflammatory response to the implanted material, called foreign body reaction (FBR). FBR may eventually lead to a fibrous encapsulation of the electrode surface. Poly(ethylene glycol) (PEG) is one of the most common low-fouling materials used to coat and protect electrode surfaces. Yet, PEG can easily undergo encapsulation and oxidative damage in long-term in vivo applications. Poly(sulfobetaine methacrylate) - poly(SBMA) - zwitterionic hydrogels may represent more promising alternatives to minimize the FBR due to their ultra-low fouling features. Here, we tested and compared the poly(SBMA) zwitterionic hydrogel coating with the PEG coating in reducing adhesion and activation of pro-inflammatory and pro-fibrotic cells to polyimide surfaces, which are early hallmarks of FBR. We aimed to coat polyimide surfaces with a hydrogel thin film and analysed the release of a model drug from the hydrogel.

We performed hydrogel synthesis, mechanical characterization and biocompatibility analysis. Cell adhesion, viability and morphology of human myofibroblasts cultured on PEG- and hydrogel-coated surfaces were evaluated through confocal microscopy-based high-content analysis (HCA). Reduced activation of pro-inflammatory human macrophages cultured on hydrogels was assessed as well as the hydrogel drug release profile.

Because of its high hydration, biocompatibility, low stiffness and ultra-low fouling characteristics the hydrogel enabled lower adhesion and activation of pro-inflammatory and pro-fibrotic cells vs. polystyrene controls, and showed a long-term release of the anti-fibrotic drug Everolimus. Furthermore, a polyimide surface was successfully coated with a hydrogel thin film.

Our soft zwitterionic hydrogel could outperform PEG as more suitable coating material of neural electrodes for mitigating the FBR. Such poly(SBMA)-based biomaterial could also be envisioned as long-term delivery system for a sustained release of anti-inflammatory and anti-fibrotic drugs in vivo.

Total joint replacement (TJR) was one of the most revolutionary breakthroughs in joint surgery. The majority studies had shown that most implants could last about 25 years, anyway, there is still variation in the longevity of implants. In US, for all the hip revisions from 2012 to 2017 in the United States, 12.0% of the patients were diagnosed as aseptic loosening. Variable studies have showed that any factor that could cause a systemic or partial bone loss, might be the risk of periprosthetic osteolysis and aseptic loosening.

Breast cancer is the most frequent malignancy in women, more than 2.1 million women were newly diagnosed with breast cancer, 626,679 women with breast cancer died in 2018. It's been reported that the mean incidence of THA was 0.29% for medicare population with breast cancer in USA, of which the incidence was 3.46% in Norwegian. However, the effects of breast cancer chemotherapy and hormonotherapy, such as aromatase inhibitors (AI), significantly increased the risk of osteoporosis, and had been proved to become a great threat to hip implants survival.

In this case, a 46-year-old female undertook chemotherapy and hormonotherapy of breast cancer 3 years after her primary THA, was diagnosed with aseptic loosening of the hip prosthesis. Her treatment was summarized and analyzed.

Breast cancer chemotherapy and hormonotherapy might be a threat to the stability of THA prosthesis. More attention should be paid when a THA paitent occurred with breast cancer. More studies about the effect of breast cancer treatments on skeleton are required.

Osteoarthritis (OA), the most prevalent chronic joint disease, represents a relevant social and economic burden worldwide. Human umbilical cord mesenchymal stem cells (HUCMSCs) have been used for injection into the joint cavity to treat OA. The aim of this article is to clarify whether Huc-MSCs derived exosomes could inhibit the progression of OA and the mechanism in this process.

A rabbit OA model was established by the transection of the anterior cruciate ligament. The effects of HUCMSCs or exosomes derived from HUCMSCs on repairing articular cartilage of knee osteoarthritis was examined by micro-CT. Immunohistochemical experiments were used to confirm the expression of relevant inflammatory molecules in OA. In vitro experiments, Transwell assay was used to assess the migration of macrophages induced by TNF-a.

Results showed that a large number of macrophages migrated in arthcular cavity in OA model in vivo, while local injection of HUCMSCs and exosomes did repair the articular cartilage. Immunohistochemical results suggested that the expression of CCL2 and CD68 in the OA rabbit model increased significantly, but was significantly reduced by HUCMSCs or exosomes. Transwell assay showed that both HUCMSCs and exosomes can effectively inhibit the migration of macrophage.

In conclusion, the exosomes derived by HUCMSCs might might rescue cartilage defects in rabbit through its anti-inflammatory effects through inhibiting CCL2.

Osteoarthritis (OA) is a common age-related degenerative joint disease, affecting 7% of the global population, more than 500 million people worldwide. Exosomes from mesenchymal stem cells (MSCs) showed promise for OA treatment, but the insufficient biological targeting weakens its efficacy and might bring side effects. Here, we report the chondrocyte-targeted exosomes synthesized via click chemistry as a novel treatment for OA.

Exosomes are isolated from human umbilical cord-derived MSCs (hUC-MSCs) using multistep ultracentrifugation process, and identified by electron microscope and nanoparticle tracking analysis (NTA). Chondrocyte affinity peptide (CAP) is conjugated on the surface of exosomes using click chemistry. For tracking, nontagged exosomes and CAP-exosomes are labeled by Dil, a fluorescent dye that highlights the lipid membrane of exosomes. To verify the effects of CAP-exosomes, nontagged exosomes and CAP-exosomes are added into the culture medium of interleukin (IL)-1β-induced chondrocytes. Immunofluorescence are used to test the expression of matrix metalloproteinase (MMP)-13.

CAP-exosomes, compared with nontagged exosomes, are more easily absorbed by chondrocytes. What's more, CAP-exosomes induced lower MMP-13 expression of chondrocytes when compared with nontagged exosomes (p<0.001).

CAP-exosomes show chondrocyte-targeting and exert better protective effect than nontagged exosomes on chondrocyte extracellular matrix. Histological and in vivo validation are now being conducted.

The quest for optimal treatment of acute distal tibiofibular syndesmotic disruptions is still in full progress. Using suture-button repair devices is one of the dynamic stabilization options, however, they may not be always appropriate for stabilization of length-unstable syndesmotic injuries. Recently, a novel screw-suture repair system was developed to address such issues. The aim of this study was to investigate the performance of the novel screw-suture repair system in comparison to a suture-button stabilization of unstable syndesmotic injuries.

Eight pairs of human cadaveric lower legs were CT scanned under 700 N single-leg axial loading in five foot positions – neutral, 15° external/internal rotation and 20° dorsi-/plantarflexion – in 3 different states: (1) pre-injured (intact); (2) injured, characterized by complete syndesmosis and deltoid ligaments cuts simulating pronation-eversion injury types III and IV, and supination-eversion injury type IV according to Lauge-Hansen; (3) reconstructed, using a screw-suture (FIBULINK, Group 1) or a suture-button (TightRope, Group 2) implants for syndesmotic stabilization, placed 20 mm proximal to the tibia plafond/joint surface. Following, all specimens were: (1) biomechanically tested over 5000 cycles under combined 1400 N axial and ±15° torsional loading; (2) rescanned. Clear space (diastasis), anterior tibiofibular distance, talar dome angle and fibular shortening were measured radiologically from CT scans. Anteroposterior, axial, mediolateral and torsional movements at the distal tibiofibular joint level were evaluated biomechanically via motion tracking.

In each group clear space increased significantly after injury (p ≤ 0.004) and became significantly smaller in reconstructed compared with both pre-injured and injured states (p ≤ 0.041). In addition, after reconstruction it was significantly smaller in Group 1 compared to Group 2 (p < 0.001). Anteroposterior and axial movements were significantly smaller in Group 1 compared with Group 2 (p < 0.001). No further significant differences were detected between the groups (p ≥ 0.113).

Conclusions

Although both implant systems demonstrate ability for stabilization of unstable syndesmotic injuries, the screw-suture reconstruction provides better anteroposterior translation and axial stability of the tibiofibular joint and maintains it over time under dynamic loading. Therefore, it could be considered as a valid option for treatment of syndesmotic disruptions.

Treatment of tibial osteomyelitis can be challenging and lengthy, with numerous complications possible during rehabilitation. We report on the usage of the Taylor Spatial Frame (TSF) for a large cohort of patients, and analyse factors that affect outcomes

Between 2015-2020, 51 patients were treated with TSF for osteomyelitis at a major trauma centre.

Demographic, infection and treatment factors of: age, smoking status, diabetes, and BMI, acute (<6 weeks post injury) or chronic (>6 weeks) osteomyelitis, bacteria isolated, time to debridement, therapy/surgery number of TSF, time TSF was in, antibiotic treatment period, time to partial weight bear (PWB) and full weight bear (FWB) prescriptions, were collected. Outcomes of complications and time to union were obtained.

Radiological union was achieved at mean 11.0 months. Mean follow up was 24.1 months. Six and three patients were further treated with fusion and amputation respectively. Mean treatment time with TSF was 12.1 months. 78% had some complications, with pin site infection, malunion, and non-union being most prevalent.

Univariate factor analysis, multicollinearity diagnostics, then multivariate model construction were performed.

Staphylococcus Epidermidis in bone debridement microbiology was significantly negatively associated with pin site infection (OR 0.093, 95% CI 0.011-0.828) and malunion (OR 0.698, 95% CI 0.573-0.849), and enterococcus with non-union (OR 0.775, 95% CI 0.656-0.916), during the treatment period. Time to union was significantly positively associated with time from admission to debridement (p=0.035), time TSF was in (p=0.021), presence of complications (p=0.045), bone loss complication(p=0.037), time to FWB prescription(p=0.001).

We have analysed the effectiveness of TSF in the treatment of tibial osteomyelitis, and elucidated important injury, treatment and rehabilitation factors that affect outcome. The negative bacterial-complication cross associations could be due to successful eradication as culture specific antibiotics were used postoperatively. Earlier patient full weight bearing could enhance callous formation leading to faster union.

Though retear rates following rotator cuff repair are well established, we set out to review current literature to determine when early retears occurred (defined as <12m following surgery), and examine which pre- and post-operative variables might affect outcome.

Pubmed, Medline, and CINAHL were searched for literature published from 2011 to 2021 using specific search terms. The inclusion criteria were studies reporting retear rates within 12 months of initial surgical repair. Exclusionary criteria were studies that included partial thickness tears, and studies that did not use imaging modalities within 12 months to assess for retears. PRISMA guidelines were followed, identifying a total of 10 papers.

A combined total of 3372 shoulders included (Mean age 56 −67 years). The most common modality used to identify early retears were ultrasound scan and MRI. 6 of the 10 studies completed imaging at 0-3 months, 6 studies imaged at 3-6 months and 6 studies imaged at 6-12 months. Across all studies, there was a 17% early retear rate (574 patients). Of these, 13% occurred by 3 months, whilst the peak for retears occurred at 3-6 months (82%) and 5% occurred at 6-12 months. The risk of retear was higher in larger tears and extensive tendon degeneration. All studies apart from one documented a return to work/sport at 6 months post-operatively. Postoperative rehabilitation does not appear to alter retear rate, although data is limited with only 1 of 10 studies allowing active range of movement before 6 weeks. Retorn tendons had poorer functional outcomes compared to intact tendons at 12m following initial repair.

The majority of early retears occur at 3-6 months and this time period should be prioritised both in rehabilitation protocols and future research. Age, tear size, and tendon degeneration were found to influence likelihood of early retears.

First-time revision acetabular components have a 36% re-revision rate at 10 years in Australia, with subsequent revisions known to have even worse results. Acetabular component migration >1mm at two years following revision THA is a surrogate for long term loosening. This study aimed to measure the migration of porous tantalum components used at revision surgery and investigate the effect of achieving press-fit and/or three-point fixation within acetabular bone.

Between May 2011 and March 2018, 55 patients (56 hips; 30 female, 25 male) underwent acetabular revision THR with a porous tantalum component, with a post-operative CT scan to assess implant to host bone contact achieved and Radiostereometric Analysis (RSA) examinations on day 2, 3 months, 1 and 2 years. A porous tantalum component was used because the defects treated (Paprosky IIa:IIb:IIc:IIIa:IIIb; 2:6:8:22:18; 13 with pelvic discontinuity) were either deemed too large or in a position preventing screw fixation of an implant with low coefficient of friction. Press-fit and three-point fixation of the implant was assessed intra-operatively and on postoperative imaging.

Three-point acetabular fixation was achieved in 51 hips (92%), 34 (62%) of which were press-fit. The mean implant to host bone contact achieved was 36% (range 9-71%). The majority (52/56, 93%) of components demonstrated acceptable early stability. Four components migrated >1mm proximally at two years (1.1, 3.2, 3.6 and 16.4mm). Three of these were in hips with Paprosky IIIB defects, including 2 with pelvic discontinuity. Neither press-fit nor three-point fixation was achieved for these three components and the cup to host bone contact achieved was low (30, 32 and 59%).

The majority of porous tantalum components had acceptable stability at two years following revision surgery despite treating large acetabular defects and poor bone quality. Components without press-fit or three-point fixation were associated with unacceptable amounts of early migration.

Reducing wear of endoprosthetic implants is still an important goal in order to increase the life time of the implant. Endoprosthesis failure can be caused by many different mechanisms, such as abrasive wear, corrosion, fretting or foreign body reactions due to wear accumulation. Especially, modular junctions exhibit high wear rates and corrosion due to micromotions at the connection of the individual components. The wear generation of cobalt-chromium-molybdenum alloys (CoCrMo) is strongly influenced by the microstructure. Therefore, the aim of this work is to investigate the subsurface phase transformation by deep rolling manufacturing processes in combination with a “sub-zero” cooling strategy.

We analyzed the influence on the phase structure and the mechanical properties of wrought CoCr28Mo6 alloy (ISO 5832-12) by a deep rolling manufacturing process at various temperatures (+25°C,-10°C,-35°C) and different normal forces (700N and 1400N). Surface (S_a,S_z) and subsurface characteristics (residual stress) as well as biological behavior were investigated for a potential implant application.

We showed that the microstructure of CoCr28Mo6 wrought alloy changes depending on applied force and temperature. The face centered cubic (fcc) phase could be transformed to a harder hexagonal-close-packed (hcp) phase structure in the subsurface. The surface could be smoothed (up to S_a = 0.387 µm±0.185 µm) and hardened (≥ 700 HV 0.1) at the same time. The residual stress was increased by more than 600% (n=3). As a readout for metabolic activity of MonoMac (MM6) and osteosarcoma (SaOS-2) cells a WST assay (n=3) was used. The cells showed no significant negative effect of the sub-zero manufacturing process.

We showed that deep rolling in combination with an innovative cooling strategy for the manufacturing process has a great potential to improve the mechanical properties of CoCr28Mo6 wrought alloy, by subsurface hardening and phase transformation for implant applications.

Physiotherapy is a critical element in successful conservative management of low back pain (LBP). The aim of this study was to develop and evaluate a system with wearable inertial sensors to objectively detect sitting postures and performance of unsupervised exercises containing movement in multiple planes (flexion, extension, rotation).

A set of 8 inertial sensors were placed on 19 healthy adult subjects. Data was acquired as they performed 7 McKenzie low-back exercises and 3 sitting posture positions. This data was used to train two models (Random Forest (RF) and XGBoost (XGB)) using engineered time series features. In addition, a convolutional neural network (CNN) was trained directly on the time series data. A feature importance analysis was performed to identify sensor locations and channels that contributed most to the models. Finally, a subset of sensor locations and channels was included in a hyperparameter grid search to identify the optimal sensor configuration and the best performing algorithm(s) for exercise classification. Models were evaluated using F1-score in a 10-fold cross validation approach.

The optimal hardware configuration was identified as a 3-sensor setup using lower back, left thigh, and right ankle sensors with acceleration, gyroscope, and magnetometer channels. The XBG model achieved the highest exercise (F1=0.94±0.03) and posture (F1=0.90±0.11) classification scores. The CNN achieved similar results with the same sensor locations, using only the accelerometer and gyroscope channels for exercise classification (F1=0.94±0.02) and the accelerometer channel alone for posture classification (F1=0.91±0.03).

This study demonstrates the potential of a 3-sensor lower body wearable solution (e.g. smart pants) that can identify proper sitting postures and exercises in multiple planes, suitable for low back pain. This technology has the potential to improve the effectiveness of LBP rehabilitation by facilitating quantitative feedback, early problem diagnosis, and possible remote monitoring.

In current practice in the UK there are three main approaches to investigating suspected scaphoid fractures not seen on initial plain film x-rays.

Our unit uses the VFC model. We aimed to evaluate its efficiency, safety, clinical outcomes and economic viability.

All patients attending the emergency department with either a confirmed or suspected scaphoid fracture between March and December 2020 were included (n=305). Of these 297 were referred to the VFC: 33 had a confirmed fracture on x-ray and 264 had a suspected fracture.

Of the suspected fractures reviewed in VFC 14% had an MRI organised directly owing to a high-risk presentation, 79% were brought for fracture clinic review and 17% discharged with an alternative diagnosis such as osteoarthritis.

Of those subsequently reviewed in fracture clinic at two weeks: 9% were treated as scaphoid fractures (based on clinical suspicion and repeat x-rays), 17% had MRI or CT imaging organised, 5% did not attend and 69% were discharged.

Overall, 17% of cases initially triaged, had further imaging – 41 MRIs and 5 CTs. MRI detected: 5% scaphoid fracture, 17% other fracture, 24% bone contusion, complete ligament tear 10%, partial ligament tear 39% and normal study 10%. The results of MRI minimally affected management. 3 patients were taken out of plaster early, 1 patient was immobilized who was not previously and no patients underwent operative management.

In the following 12-month period one patient re-presented with a hand or wrist issue.

This approach avoided 218 MRIs, equating to £24000 and 109 hours of scanner time.

VFC triage and selective use of MRI scanning is a safe, efficient and cost-effective method for the management suspected scaphoid fractures. This can be implemented in units without the resource to MRI all suspected scaphoid fractures from the emergency department.

Recently, a new suture was designed to minimize laxity in order to preserve consistent tissue approximation while improving footprint compression after tendon repair. The aims of this study were: (1) to compare the biomechanical competence of two different high strength sutures in terms of slippage and failure load, (2) to investigate the influence of both knots number and different media (air, saline and fat) on the holding capacity of the knots.

Alternating surgical knots of two different high-strength sutures (group1: FibreWire; group2: DynaCord; n = 105) were tied on two roller bearings with 50N tightening force. Biomechanical testing was performed in each medium applying ramped monotonic tension to failure defined in terms of either knot slippage or suture rupture. For each group and medium, seven specimens with either 3, 4, 5, 6, or 7 knots each were tested, evaluating their knot slippage and ultimate load to failure. The minimum number of knots preventing slippage failure and thus resulting in suture rupture was determined in each group and medium, and taken as a criterium for better performance when comparing the groups.

In each group and medium failure occurred via suture rupture in all specimens for the following minimum knot numbers: group1: air – 7, saline – 7, fat – 7; group2: air – 6; saline – 4; fat – 5. The direct comparison between the groups when using 7 knots demonstrated significantly larger slippage in group1 (6.5 ± 2.2 mm) versus group2 (3.5 ± 0.4 mm) in saline (p < 0.01) but not in the other media (p ≥0.52). Ultimate load was comparable between the two groups for all three media (p ≥ 0.06).

The lower number of required knots providing sufficient repair stability, smaller slippage levels and identical suture strength, combined with the known laxity alleviation effect demonstrate advantages of DynaCord versus FibreWire.

The COVID-19 pandemic necessitated a pivot to online learning for many traditional, hands-on subjects such as anatomy. This, coupled with the increase in online education programmes, and the reduction of time students spend in anatomy dissection rooms, has highlighted a real need for innovative and accessible learning tools. This study describes the development of a novel 3-dimensional (3D), interactive anatomy teaching tool using structured light scanning (SLS) technology. This technique allows the 3D shape and texture of an object to be captured and displayed online, where it can be viewed and manipulated in real-time.

Human bones of the upper limb, vertebrae and whole skulls were digitised using SLS using Einscan Pro2X/H scanners. The resulting meshes were then post-processed to add the captured textures and to remove any extraneous information. The final models were uploaded into Sketchfab where they were orientated, lit and annotated. To gather opinion on these models as effective teaching tools, surveys were completed by anatomy students (n=35) and anatomy educators (n=8). Data was collected using a Likert scale response, as well as free text answers to gather qualitative information.

3D scans of the scapula, humerus, radius, ulna, vertebrae and skull were successfully produced by SLS. Interactive models were produced via scan data in Sketchfab and successfully annotated to provide labelled 3D models for examination. 94% of survey respondents agreed that the interactive models were easy to use (n=35, 31% agree and 63% strongly agree) and 97% agreed that the 3D interactive models were more useful than 2D images for learning bony anatomy (n=35; 26% agree and 71% strongly agree).

This initial study has demonstrated a suitable proof-of-concept for SLS technology as a useful technique for producing 3D interactive online tools for learning and teaching bony anatomy. Current studies are focussed on determining the SLS accuracy and the ability of SLS to capture soft tissue/joints. We believe that this tool will be a useful technique for generating online 3D interactive models to study orthopaedic anatomy.

Primary implant stability is critical for osseointegration and subsequent implant success. Small displacements on the screw/bone interface are necessary for implant success, however, larger displacements can propagate cracks and break anchorage points which causes the screw to fail. Limited information is available on the progressive degradation of stability of an implanted bone screw since most published research is based on monotonic, quasi-static loading [1]. This study aims to address this gap in knowledge.

A total of 100 implanted trabecular screws were tested using multi-axial loading test set-up. Screws were loaded in cycles with the applied force increasing 1N in each load cycle. In every load cycle, Peak forces, displacements, and stiffness degradation (calculated in the unloading half of the cycle) where recorded. 10 different loading configurations where tested.

The damage vs displacement shows a total displacement at the point of failure between 0.3 and 0.4 mm while an initial stiffness reduction close to 40%. It is also shown that at a displacement of ~0.1 mm, the initial stiffness of every sample had degraded by 20% (or more) meaning that half of the allowable degradation occurred in the first 25-30% of the total displacement.

Other studies on screw overloading [1] suggests similar results to our concerning initial stiffness degradation at the end of the loading cycle. Our results also show that the initial stiffness degrades faster with relatively small deformations suggesting that the failure point of an implanted screw might occur before the common failure definition (pull-out force, for example). These results are of great significance since primary implant stability is better explained by the stiffness of the construct than by its failure point.

Bone turnover and microdamage are impacted by skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This study aimed to establish an understanding of microdamage accumulation and load to failure in healthy and osteolytic vertebrae following cancer treatment (stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX)).

Forty-two 6-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo) were studied; 22 were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Animals were randomly assigned to four groups: untreated (healthy=5, osteolytic=6), SBRT on day 14 (healthy=6, osteolytic=6), ZA on day 7 (healthy=4, osteolytic=5), and DTX on day 14 (healthy=5, osteolytic=5). Animals were euthanized on day 21. L1-L3 motion segments were compression loaded to failure and force-displacement data recorded. T13 vertebrae were stained with BaSO₄ and µCT imaged (90kVp, 44uA, 4.9µm) to visualize microdamage location and volume. Damage volume fraction (DV/BV) was calculated as the ratio of BaSO₄ to bone volume. Differences in mean load-to-failure were compared using three-way ANOVA (disease status, treatment, cells injected). Differences in mean DV/BV between treatment groups were compared using one-way ANOVA.

Treatment had a significant effect on load-to-failure (p=0.004) with ZA strengthening the healthy and osteolytic vertebrae. Reduced strength post SBRT seen in the metastatic (but not the healthy) group may be explained by greater tumor involvement secondary to higher cell injection concentrations. Untreated metastatic samples had higher DV/BV (16.25±2.54%) compared to all treatment groups (p<0.05) suggesting a benefit of treatment to bone quality.

Focal and systemic cancer treatments were shown to effect load-to-failure and microdamage accumulation in healthy and osteolytic vertebrae. Developing a better understanding of how treatments effect bone quality and mechanical stability is critical for effective management of patients with spinal metastases.

To investigate the utility of virtual reality (VR) simulators in improving surgical proficiency in Orthopaedic trainees for complex procedures and techniques.

Fifteen specialty surgeons attending a London Orthopaedic training course were randomised to either the VR (n = 7) or control group (n = 8). All participants were provided a study pack comprising an application manual and instructional video for the Trochanteric Femoral Nail Advanced (TFNA) procedure. The VR group underwent additional training for TFNA using the DePuy Synthes (Johnson and Johnson) VR simulator. All surgeons were then observed applying the TFNA in a Sawbones model and assessed by a blinded senior consultant using three metrics: time to completion, 22-item procedure checklist and 5-point global assessment scale.

Participant demographics for the VR and control groups were similar in context of age (mean [SD]: VR group, 31.0 [2.38] years; control group, 30.6 [2.39] years), gender (VR group, 5 [71%] men; control group, 8 [100%] men) and prior experience with TFNA (had applied TFNA as primary surgeon: VR group, 6 [86%]; control group, 7 [88%]). Although statistical significance was not reached, the VR group, on average, outperformed the control group on all three metrics. They completed the TFNA procedure faster (mean [SD]: 18.2 [2.16] minutes versus 19.78 [1.32] minutes; p<0.189), performed a greater percentage of steps correctly (79% versus 66%; p<0.189) and scored a higher percentage on the global assessment scale (75% versus 65%; p<0.232).

VR simulators offer a safe and accessible means for Orthopaedic trainees to prepare for and supplement their theatre-based experience. It is vital, therefore, to review and validate novel simulation-based systems and in turn facilitate their improvement. We intend to increase our sample size and expand this preliminary study through a second upcoming surgical course for Orthopaedic trainees in London.

Open talus fracture are notoriously difficult to manage and they are commonly associated with a high level of complications including non-union, avascular necrosis and infection. Currently, the management of such injuries is based upon BOAST 4 guidelines although there is no suggested definitive management, thus definitive management is based upon surgeon preference. The key principles of open talus fracture management which do not vary between surgeons, however, there is much debate over whether the talus should be preserved or removed after open talus fracture/dislocation and proceeded to tibiocalcaneal fusion.

A review of electronic hospital records for open talus fractures from 2014-2021 returned foureen patients with fifteen open talus fractures. Seven cases were initially managed with ORIF, five cases were definitively managed with FUSION, while the others were managed with alternative methods. We collected patient's age, gender, surgical complications, surgical risk factors and post-treatment functional ability and pain and compliance with BOAST guidelines. The average follow-up of the cohort was four years and one month. EQ-5D-5L and FAAM-ADL/Sports score was used as a patient reported outcome measure. Data was analysed using the software PRISM.

Comparison between FUSION and ORIF groups showed no statistically significant difference in EQ-5D-5L score (P = 0.13), FAAM-ADL (P = 0.20), FAAM-Sport (P = 0.34), infection rate (P = 0.55), surgical times (P = 0.91) and time to weight bearing (P = 0.39), despite a higher proportion of polytrauma and Hawkins III and IV fractures in the FUSION group.

FUSION is typically used as second line to ORIF or failed ORIF. However, there are a lack of studies that directly compared outcome in open talus fracture patients definitively managed with FUSION or ORIF. Our results demonstrate for the first time, that FUSION may not be inferior to ORIF in terms of patient functional outcome, infection rate, and quality-of-life, in the management of patients with open talus fracture patients. Of note, as open talus fractures have increased risks of complications such as osteonecrosis and non-union, FUSION should be considered as a viable option to mitigate these potential complications in these patients.

Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution.

Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection.

We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well.

Helical plates are preferably used for proximal humeral shaft fracture fixation and potentially avoid radial nerve irritation as compared to straight plates. Aims:(1) to investigate the safety of applying different long plate designs (straight, 45°-, 90°-helical and ALPS) in MIPO-technique to the humerus. (2) to assess and compare their distances to adjacent anatomical structures at risk.

MIPO was performed in 16 human cadaveric humeri using either a straight plate (group1), a 45°-helical (group2), a 90°-helical (group3) or an ALPS (group4). Using CT-angiography, distances between brachial arteries and plates were evaluated. Following, all specimens were dissected, and distances to the axillary, radial and musculocutaneous nerve were evaluated.

None of the specimens demonstrated injuries of the anatomical structures at risk after MIPO with all investigated plate designs. Closest overall distance (mm(range)) between each plate and the radial nerve was 1(1-3) in group1, 7(2-11) in group2, 14(7-25) in group3 and 6(3-8) in group4. It was significantly longer in group3 and significantly shorter in group1 as compared to all other groups, p<0.001. Closest overall distance (mm(range)) between each plate and the musculocutaneous nerve was 16(8-28) in group1, 11(7-18) in group2, 3(2-4) in group3 and 6(3-8) in group4. It was significantly longer in group1 and significantly shorter in group3 as compared to all other groups, p<0.001. Closest overall distance (mm(range)) between each plate and the brachial artery was 21(18-23) in group1, 7(6-7) in group2, 4(3-5) in group3 and 7(6-7) in group4. It was significantly longer in group1 and significantly shorter in group3 as compared to all other groups, p<0.021.

MIPO with 45°- and 90°-helical plates as well as ALPS is safely feasible and showed a significant greater distance to the radial nerve compared to straight plates. However, distances remain low, and attention must be paid to the musculocutaneous nerve and the brachial artery when MIPO is used with ALPS, 45°- and 90°-helical implants. Anterior parts of the deltoid insertion will be detached using 90°-helical and ALPS implants in MIPO-technique.

Fracture related infections (FRI) are debilitating complications of musculoskeletal trauma surgery that can result in permanent functional loss or amputation. This study aims to determine risk factors associated with FRI treatment failure, allowing clinicians to optimise them prior to treatment and identify patients at higher risk.

A major trauma centre database was retrospectively reviewed over a six-year period. Of the 102 patients identified with a FRI (66 male, 36 female), 29.4% (n=30) had acute infections (onset <6 weeks post-injury), 34.3% (n=35) had an open fracture. Open fractures were classified using Gustilo-Anderson (GA) classification (type 2:n=6, type 3A:n=16, type 3B:n=10, type 3C:n=3). Patients with periprosthetic infections of the hip and knee joint, those without prior fracture fixation, soft tissue infections, diabetic foot ulcers, pressure sore infections, patients who died within one month of injury, <12 months follow-up were excluded.

FRI treatment failure was defined as either infection recurrence, non-union, or amputation. Lifestyle, clinical, and intra-operative data were documented via retrospective review of medical records. Factors with a P-value of p<0.05 in univariate analysis were included in a stepwise multivariate logistic regression model.

FRI treatment failure was encountered in 35.3% (n=36). The most common FRI site was the femoral shaft (16.7%; n=17), and 15.7% (n=16) presented with signs of systemic sepsis. 20.6% (n=21) had recurrent infection, 9.8% (n=10) had non-union, and 4.9% (n=5) required an amputation. The mean age at injury was 49.71 years old. Regarding cardiovascular risk factors, 37 patients were current smokers (36.3%), 31 patients were diabetics (30.4%), and 32 patients (31.4%) were obese (BMI≥30.0). Average follow-up time was 2.37 (range: 1.04-5.14) years. Risk factors for FRI treatment failure were BMI>30, GA type 3c, and implant retention.

Given that FRI treatment in 35.3% (36/102) ended up in failure, clinicians need to take into account the predictive variables analysed in this study, and implement a multidisciplinary team approach to optimise these factors. This study could aid clinicians to redirect efforts to improve high risk patient management, and prompt future studies to trial adjuvant technologies for patients at higher risk of failure.

Arthritis is a common and debilitating disease and is associated with an increased fall risk. The purpose of this study was to examine the effect of impacted joint and limb on fall risk as measured by the margin of stability (MOS).

There were 110 participants, including healthy controls (HC; n=30), ankle arthritis (AA; n=30), knee arthritis (KA; n=20) and hip arthritis (HA; n=30) patients. All protocols were Institutional Review Board approved and all participants signed informed consent. Participants walked approximately 6 meters at a self-selected pace. MOS was calculated in the foot coordinate system in the anterior/posterior (AP) and medial/lateral (ML) directions at heel strike. A one-way ANOVA was used to examine group effects (HC, AA, KA, HA) on gait speed. A two-way repeated measures ANOVA was used to examine the effects of limb (Non-Surgical, Surgical) and group on AP and ML MOS.

HC had the fastest gait speed (1.40±0.24 m/s; p<0.001) when compared to AA (0.85±0.24 m/s), KA (0.94±0.22 m/s) and HA (1.05±0.22 m/s). HA participants had a greater gait speed compared to AA (p=0.004). AP MOS was greater in the surgical limb compared to the non-surgical limb for AA (p<0.001) and HA (p<0.001). AP MOS was smaller in HC compared to AA, KA, and HA, regardless of limb (p<0.030). AP MOS was similar between AA, KA, and HA for the non-surgical limb (p>0.194) and the surgical limb (p>0.096). ML MOS was greater in the surgical compared to non-surgical limb (p=0.003). ML MOS was smaller in KA participants compared to all other groups (p<0.001).

Our results demonstrate stability during gait varies between limbs in arthritis patients, with a more conservative pattern for the surgical limb and suggest KA may be at an increased risk of falls with a smaller ML MOS.

Total Knee Arthroplasty (TKA) improves the quality of life of osteoarthritic and rheumatoid arthritis patients, however, is associated with moderate to severe postoperative pain. There are multiple methods of managing postoperative pain that include epidural anesthesia but it prevents early mobilization and results in postoperative hypotension and spinal infection. Controlling local pain pathways through intra-articular administration of analgesics is a novel method and is inexpensive and simple. Hence, we assess the effects of postoperative epidural bupivacaine injection along with intra-articular injection in total knee replacement patients.

The methodology included 100 patients undergoing TKA randomly divided into two groups, one administered with only epidural bupivacaine injection and the other with intra-articular cocktail injection. The results were measured based on a 10-point pain assessment scale, knee's range of motion (ROM), and Lysholm knee score.

The VAS score was lower in the intra-articular cocktail group compared to the bupivacaine injection group until the end of 1-week post-administration (p<0.01). Among inter-group comparisons, we observed that the range of motion was significantly more in cocktail injection as compared to the bupivacaine group till the end of one week (p<0.05). Lysholm's score was significantly more in cocktail injection as compared to the bupivacaine group till the end of one week (p<0.05).

Our study showed that both epidural bupivacaine injection and intra-articular injection were effective in reducing pain after TKA and have a comparable functional outcome at the end of 4 weeks follow up. However, the pain relief was faster in cases with intra-articular injection, providing the opportunity for early rehabilitation. Thus, we recommend the use of intra-articular cocktail injection for postoperative management of pain after total knee arthroplasty, which enables early rehabilitation and faster functional recovery of these patients.

As peri-prosthetic aseptic loosening is one of the main causes of implant failure, inhibiting wear particles induced macrophages inflammation is considered as a promising therapy for AL to expand the lifespan of implant. Here, we aim at exploring the role of p110δ, a member of class IA PI3K family, and Krüppel-like factor 4 (KLF4) in titanium particles (TiPs) induced macrophages-inflammation and osteolysis.

Firstly, IC87114, the inhibitor of p110δ and siRNA targeting p110δ were applied and experiments including ELISA and immunofluorescence assay were conducted to explore the role of p110δ. Sequentially, KLF4 was predicted as the transcription factor of p110δ and the relation was confirmed by dual luciferase reporter assay. Next, assays including RT-PCR, western blotting and flow cytometry were performed to ensure the specific role of KLF4. Finally, TiPs-induced mice cranial osteolysis model was established, and micro-CT scanning and immunohistochemistry assay were performed to reveal the role of p110δ and KLF4 in vivo.

Here, we found that p110δ was upregulated in TiPs-stimulated macrophages. The inhibition of p110δ or knockdown of p110δ could significantly dampen the TiPs-induced secretion of TNFα and IL-6. Further mechanistic studies confirmed that p110δ was responsible for TNFα and IL-6 trafficking out of Golgi complex without affecting their expression in TiPs-treated macrophages. Additionally, we explored the upstream regulators and confirmed that Krüppel-like factor 4 (KLF4) was the transcription repressor of p110δ. Apart from that, KLF4, targeted by miR-92a, could also attenuate TiPs-induced inflammation by mediating NF-κB pathway and M1/M2 polarization. By the establishment of TiPs-induced mice cranial osteolysis model, we found that KLF4 knockdown exacerbated TiPs-induced osteolysis which was strikingly ameliorated by knockdown of p110δ.

In summary, our study suggests the key role of miR-92a/KLF4/p110δ signal in TiPs-induced macrophages inflammation and osteolysis.

This study aims to assess the changes in mechanical behaviour over time in ‘haemarthritic’ articular cartilage compared to ‘healthy’ articular cartilage.

Pin-on-plate and indentation tests were used to determine the coefficient of friction (COF) and deformation of ‘healthy’ and ‘haemarthritic articular cartilage. Osteochondral pins (8 mm) were extracted from porcine tali and immersed in exposure fluid for two hours prior to test. Pins were articulated against a larger bovine femoral plate for 3600 seconds under a load of 50 N. Osteochondral pins (8 mm) were loaded during indentation testing for 3600 seconds under a load of 0.25 N. To mimic the effect of a joint bleed in vitro; serum, whole blood and 50% v/v were used as exposure and lubricant fluids. COF and deformation were expressed as mean (n=3) and statistically analysed using a one-way ANOVA and post-hoc Tukey test (p>0.05).

The serum condition yielded a COF of 0.0428 ± 0.02 with 0.08mm ± 0.04 deformation. The 50% v/v condition produced a higher COF of 0.0485 ± 0.02 and 0.21mm ± 0.04 deformation. The lowest COF and deformation were produced by the whole blood condition (0.0292 ± 0.02 and 0.06mm ± 0.006 respectively). Statistical analysis indicated no significant difference across the friction test conditions but a significant difference across all indentation test conditions (ANOVA, p>0.05). Combination of creep deformation and wear was observed on the articular surface up to 24 hours post-test in 50% v/v and whole blood conditions.

The average haemophilia patient can experience multiple joint bleeds per year of which this study demonstrates the effect of just one joint bleed. This study has provided evidence of potential reversible and irreversible mechanical changes to articular cartilage surface during a joint bleed.

Mesenchymal stem cells (MSC) have potent immunomodulatory and regenerative effects via soluble factors. One approach to improve stem cell-based therapies is encapsulation of MSC in hydrogels based on natural proteins such as collagen and fibrin, which play critical roles in bone healing. In this work, we comparatively studied the influence of collagen and fibrin hydrogels of varying stiffness on the paracrine interactions established by MSC with macrophages and osteoblasts.

Type I collagen and fibrin hydrogels in a similar stiffness range loaded with MSC from donants were prepared by modifying the protein concentration. Viability and morphology of MSC in hydrogels as well as cell migration rate from the matrices were determined. Paracrine actions of MSC in hydrogels were evaluated in co-cultures with human macrophages from healthy blood donors or with osteoblasts from bone explants of patients with osteonecrosis of the femoral head.

Lower matrix stiffness resulted in higher MSC viability and migration. Cell migration rate from collagen hydrogels was higher than from fibrin matrices. The secretion of the immunomodulatory factors interleukin-6 (IL-6) and prostaglandin E₂ (PGE₂) by MSC in both collagen and fibrin hydrogels increased with increasing matrix stiffness. Tumor necrosis factor-α (TNF-α) secretion by macrophages cultured on collagen hydrogels was lower than on fibrin matrices. Interestingly, higher collagen matrix stiffness resulted in lower secreted TNF-α while the trend was opposite on fibrin hydrogels. In all cases, TNF-α levels were lower when macrophages were cultured on hydrogels containing MSC than on empty gels, an effect partially mediated by PGE₂. Finally, mineralization capacity of osteoblasts co-cultured with MSC in hydrogels increased with increasing matrix stiffness, although this effect was more notably for collagen hydrogels.

Paracrine interactions established by MSC in hydrogels with macrophages and osteoblasts are regulated by matrix composition and stiffness.

Access to health care, including physiotherapy, is increasingly occurring through virtual formats. At-home adherence to physical therapy programs is often poor and few tools exist to objectively measure low back physiotherapy exercise participation without the direct supervision of a medical professional. The aim of this study was to develop and evaluate the potential for performing automatic, unsupervised video-based monitoring of at-home low back physiotherapy exercises using a single mobile phone camera.

24 healthy adult subjects performed seven exercises based on the McKenzie low back physiotherapy program while being filmed with two smartphone cameras. Joint locations were automatically extracted using an open-source pose estimation framework. Engineered features were extracted from the joint location time series and used to train a support vector machine classifier (SVC). A convolutional neural network (CNN) was trained directly on the joint location time series data to classify exercises based on a recording from a single camera. The models were evaluated using a 5-fold cross validation approach, stratified by subject, with the class-balanced accuracy used as the performance metric.

Optimal performance was achieved when using a total of 12 pose estimation landmarks from the upper and lower body, with the SVC model achieving a classification accuracy of 96±4% and the CNN model an accuracy of 97±2%.

This study demonstrates the feasibility of using a smartphone camera and a supervised machine learning model to effectively assess at-home low back physiotherapy adherence. This approach could provide a low-cost, scalable method for tracking adherence to physical therapy exercise programs in a variety of settings.

To address the current challenge of anterior cruciate ligament (ACL) reconstruction, this study is the first to fabricate a braided collagen rope (BCR) which mimics native hamstring for ACL reconstruction. The study aims to evaluate the biological and biomechanical properties of BCR both in vivo and vitro.

Rabbit ACL reconstruction model using collagen rope and autograft (hamstring tendon) was conducted. The histological and biomechanical evaluations were conducted at 6-, 12-, 18, 26-week post-operation. In vitro study included cell morphology analysis, cell function evaluation and RNA sequencing of the tenocytes cultured on BCR. A cadaver study was also conducted to verify the feasibility of BCR for ACL reconstruction.

BCR displays satisfactory mechanical strength similar to hamstring graft for ACL reconstruction in rabbit. Histological assessment showed BCR restore ACL morphology at 26 weeks similar to native ACL. The superior dynamic ligamentization in BCR over autograft group was evidenced by assessment of cell and collagen morphology and orientation. The in vitro study showed that the natural collagen fibres within BCR enables to signal the morphology adaptation and orientation of human tenocytes in bioreactor. BCR enables to enhance cell proliferation and tenogenic expression of tenocytes as compared to hydrolysed collagen. We performed an RNA-Sequencing (RNA-seq) experiment where RNA was extracted from tenocyte seeded with BCR. Analysis of enriched pathways of the up-regulated genes revealed that the most enriched pathways were the Hypoxia-inducible factor 1-alpha (HIF1A) regulated networks, implicating the possible mechanism BCR induced ACL regeneration. The subsequent cadaver study was conducted to proof the feasibility of BCR for ACL reconstruction.

This study demonstrated the proof-of-concept of bio-textile braided collagen rope for ACL reconstruction, and the mechanism by which BCR induces natural collagen fibres that positively regulate morphology and function of tenocytes.

In-office surgeries have the potential to offer high quality medical care in a more efficient, cost-effective setting than outpatient surgical centers for certain procedures. The primary concerns with operating on patients in the office setting are insufficient sterility and lack of appropriate resources in case of excessive bleeding or other surgical complications. This study serves to investigate these concerns and determine whether in-office hand surgeries are safe and clinically effective.

A retrospective review of patients who underwent minor hand operations in the office setting between December 2020 and December 2021 was performed. The surgical procedures included in this analysis are needle aponeurotomy, trigger finger release, mass/foreign body removal and reduction of hand/wrist fracture with or without percutaneous pinning.

No major complications requiring extended observation or hospital admission occurred. 122 of the 132 patients (92.4%) were successfully treated with no complications and only mild symptoms within one month of surgery. Five patients (3.8%) returned to the office for pain, inflammation and/or stiffness of the affected finger, with two of the five returning due to osteoarthritis and/or pseudogout flare-ups. Five additional patients returned due to incomplete treatment with continued presence of Dupuytren's contracture (3), trigger finger (1) or infected foreign body (1). One patient (0.8%) developed infection, due to incomplete removal of an infected foreign body, which was subsequently treated with antibiotics and complete foreign body removal.

The absence of major complications and high success rate for minor hand procedures shows the high degree of safety and efficacy which can be achieved via the in-office setting for select procedures. While proper patient selection is key, our result shows the in-office procedure room setting can offer the necessary elements of sterility and hemostatic support for several common hand surgeries.

Extensor mechanism and abductor reconstructions in total joint arthroplasty are problematic. Growing tendon into a metallic implant would have great reconstructive advantages. With the introduction of porous metal implants, it was hoped that tendons could be directly attached to implants. However, the effects of the porous metal structure on tissue growth and pore penetration is unknown. In this rat model, we investigated the effect of pore size on tendon repair fixation using printed titanium implants with differing pore sizes.

There were four groups of six Sprague Dawley rats (n = 28) plus control (n=4). Implants had pore sizes of 400µm (n=8), 700µm (n=8), and 1000µm (n=8). An Achilles tendon defect was created, and the implant positioned and sutured between the cut ends. Harvest occurred at 12-weeks. Half the specimens underwent tensile load to failure testing, the other half fixed and processed for hard tissue analysis.

Average load to failure was 72.6N for controls (SD 10.04), 29.95N for 400µm (SD 17.95), 55.08N for 700µm (SD 13.47), and 63.08N for 1000µm (SD 1.87). The load to failure was generally better in the larger pore sizes. Histological evaluation showed that there was fibrous tendon tissue within and around the implant material, with collagen fibers organized in bundles. This increases as the pore diameter increases.

Printing titanium implants allows for precise determination of pore size and structure. Our results showed that tendon repair utilizing implants with 700µm and 1000µm pores exhibited similar load to failure as controls. Using a defined pore structure at the attachment points of tendons to implants may allow predictable tendon to implant reconstruction at the time of revision arthroplasty.

Neoangiogenesis drives the replacement of mineralised cartilage by trabecular bone during bone growth regulated by molecules like e.g. VEGF, OPG and RANKL. The Heparan sulfate proteoglycan Syndecan-1 (Sdc1) plays a role in the interaction of osteoclasts and osteoblasts and the development of blood vessels. We expected Sdc1 to have an influence on bone structure and vessel development. Therefore, bone structure and angiogenesis at the growth plate in mice was compared and the influence of Syndecan-1 deficiency was characterised.

Animals: Femura of male and female C57BL/6 WT (5♀, 6♂) and Sdc1-/- (9♀, 5♂) mice were used for native bone analysis at 4 month age. Histology: Bone structure was analysed using microCT scans with a resolution of 9µm. Vascularisation was visualised using an anti-Endomucin antibody in 80µm thick cryosections. In vitro angiogenesis: Bone marrow isolates were used to generate endothelial progenitor cells by sequential cultivation on fibronectin. Microvessel development was analysed 4h after plating on matrigel.

Bone structure in male Sdc1 deficient mice was significantly reduced compare to male WT, whereas female mice of both genotypes did not differ. Sdc1 deficient mice at the age of 4 month showed a high decrease in the number of vessel bulbs at the chondro-osseous border (growth plate) compared to WT mice. However, no sex related differences were shown. Quantification of microvessel outgrowth of endothelial cells revealed a decreased amount of sprouting, but increased length of microvessels of Sdc1-/- cells compared to WT.

Syndecan-1 has a significant impact on neoangiogenesis at the chondro-osseous border of the native bone, but the impact of Syndecan-1 deficiency on the loss of bone structure was significantly higher in male mice. This emphasises the importance to further characterise the function of Syndecan-1 regulated processes during enchondral ossification in a sex dependent manner.

In this study, we developed biocompatible adhesive which enables implanted chondrogenic-enhanced hASCs being strongly fixed to the lesion site of defected cartilage.

The bioengineered mussel adhesive protein (MAP) was produced and purified using a bacterial expression system as previously reported. The cell encapsulated coacervate was formulated with two polyelectrolyte, the MAP and 723kDa hyaluronic acid (HA). MAP formed liquid microdroplets with HA and subsequently gelated into microparticles, which is highly viscous and strongly adhesive.

The MAP with chondro-induced hASCs were implanted on the osteochondral defect created in the patellar groove/condyle of OA-induced rabbits. Rabbits were allocated to three different groups as follows: Group1 – Fibrin only; Group2 – Fibrin with hASCs (1.5×10⁶ chondro-induced hASCs); Group3; MAP with hASCs.

The implanted cells were labeled with a fluorescent dye for in vivo visualization. After 35 days, fluorescent signals were more potently detected for MAP with hASCs group than Fibrin with hASCs group in osteochondral defect model. Moreover, histological assessment showed that MAP with hASCs group had the best healing and covered with hyaline cartilage-like tissue. The staining image shows that MAP with hASCs group were filled with perfectly differentiated chondrocytes. Although Fibrin with hASCs group had better healing than fibrin only group, it was filled with fibrous cartilage which owes its flexibility and toughness. As MAP with hASCs group has higher possibility of differentiating to complete cartilage, Fibrin only group and Fibrin with hASCs group have failed to treat OA by rehabilitating cartilage. In order to clarify the evidence of remaining human cell proving efficacy of newly developed bioadhesive, human nuclear staining was proceeded with sectioned rabbit cartilage tissue. The results explicitly showed MAP with hASCs group have retained more human cells than Fibrin only and Fibrin with hASCs groups.

We investigated the waterproof bioadhesive supporting transplanted cells to attach to defect lengthily in harsh environment, which prevents cells from leaked to other region of cartilage. Collectively, the newly developed bio-adhesive, MAP, could be successfully applied in OA treatment as a waterproof bioadhesive with the capability of the strong adhesion to target defect sites.

Using deep learning and image processing technology, a standardized automatic quantitative analysis systerm of lumbar disc degeneration based on T2MRI is proposed to help doctors evaluate the prognosis of intervertebral disc (IVD) degeneration.

A semantic segmentation network BianqueNet with self-attention mechanism skip connection module and deep feature extraction module is proposed to achieve high-precision segmentation of intervertebral disc related areas. A quantitative method is proposed to calculate the signal intensity difference (SI) in IVD, average disc height (DH), disc height index (DHI), and disc height-to-diameter ratio (DHR). According to the correlation analysis results of the degeneration characteristic parameters of IVDs, 1051 MRI images from four hospitals were collected to establish the quantitative ranges for these IVD parameters in larger population around China.

The average dice coefficients of the proposed segmentation network for vertebral bodies and intervertebral discs are 97.04% and 94.76%, respectively. The designed parameters of intervertebral disc degeneration have a significant negative correlation with the Modified Pfirrmann Grade. This procedure is suitable for different MRI centers and different resolution of lumbar spine T2MRI (ICC=.874~.958). Among them, the standard of intervertebral disc signal intensity degeneration has excellent reliability according to the modified Pfirrmann Grade (macroF1=90.63%~92.02%).

we developed a fully automated deep learning-based lumbar spine segmentation network, which demonstrated strong versatility and high reliability to assist residents on IVD degeneration grading by means of IVD degeneration quantitation.

This study aims to compare the outcomes of Volar locking plating (VLP) versus percutaneous Kirschner wires (K-wire) fixation for surgical management of distal radius fractures.

We systematically searched multiple databases, including MEDLINE for randomized controlled trials (RCTs) comparing outcomes of VLP fixation and K-wire for treatment of distal radius fracture in adults. The methodological quality of each study was assessed by the Cochrane Risk of Bias tool. Patient-reported outcomes, functional outcomes, and complications at 1 year follow up were evaluated. Meta-analysis was performed using random-effects models and results presented as risk ratios (RRs) or mean differences (MDs) with 95% confidence interval (CI).

13 RCTs with 1336 participants met the inclusion criteria. Disabilities of the Arm, Shoulder and Hand (DASH) scores were significantly better for VLP fixation (MD= 2.15; 95% CI, 0.56-3.74; P = 0.01; I2=23%). No significant difference between the two procedures for grip strength measured in kilograms (MD= −3.84; 95% CI,-8.42-0.74; P = 0.10; I2=52%) and Patient-Rated Wrist Evaluation (PRWE) scores (MD= −0.06; 95% CI,-0.87-0.75; P = 0.89; I2=0%). K-wire treatment yielded significantly improved extension (MD= −4.30; P=0.04) but with no differences in flexion, pronation, supination, and radial deviation (P >0.05). The risk of complications and rate of reoperation were similar for the two procedures (P >0.05).

This meta-analysis suggests that VLP fixation improves DASH score at 12 months follow up, however, the difference is small and unlikely to be clinically important. Existing literature does not provide sufficient evidence to demonstrate the superiority of either VLP or K-wire treatment in terms of patient-reported outcomes, functional outcomes, and complications.

Osteoporotic fracture has become a major problem in ageing population and often requires prolonged healing time. Low Intensity Pulsed Ultrasound (LIPUS) can significantly enhance fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). DMP1 in osteocytes is responsible for maintaining LCN and mineralisation. This study aims to investigate osteocyte-specific DMP1's role in enhanced osteoporotic fracture healing in response to mechanical stimulation.

Bilateral ovariectomy was performed in 6-month-old female SD rats to induce osteoporosis. Metaphyseal fracture was created at left distal femur using oscillating micro-saw. Rats were randomised to groups: (1) DMP1 KD, (2) DMP1 KD + LIPUS, (3) Control, or (4) Control + LIPUS, where KD stands for knockdown by injection of shRNA into marrow cavity 2 weeks before surgery. Assessments included weekly radiography, microCT and immunohistochemistry on DMP1, E11, FGF23 and sclerostin.

DMP1 KD significantly impaired LIPUS-accelerated fracture healing when comparing KD + LIPUS group to Control + LIPUS group. The X-ray relative opacity showed less tissue growth at all timepoints (Week 1, 3 & 6; p=0.000, 0.001 and 0.003 respectively) and the bone volume fraction was decreased after DMP1 KD at Week 3 (p=0.006). DMP1 KD also significantly altered the expression levels of osteocyte-specific DMP1, E11, FGF23 and sclerostin during healing process.

The lower relative opacity and bone volume fraction in DMP1 KD groups indicated that knockdown of DMP1 was associated with poorer fracture healing process compared to non-knockdown groups. The similar results between knockdown group with and without LIPUS showed that blockage of DMP1 would negate LIPUS-induced enhancement on fracture healing.

Acknowledgment: General Research Fund (Ref: 14113018)

The pelvic girdle and spine vertebral column work as a long chain influenced by pelvic tilt. Spinal deformities or other musculoskeletal conditions may cause patients to compensate with excessive pelvic tilt, producing alterations in the degree of lumbar lordosis and subsequently causing pain. The objective of this study is to assess the effect of open and closed chain anterior or posterior pelvic tilt on lumbar spine kinematics using an in vitro cadaveric spine model.

Three human cadaveric spines with intact pelvis were suspended with the skull fixed in a metal frame. Optotrak 3D motion system tracked real-time coordinates of pin markers on the lumbar spine. A force-torque digital gage applied consistent force to standardize the acetabular or sacral axis’ anterior and posterior pelvic tilt during simulated open and closed chain movements, respectively.

In closed chain PPT, significant differences in relative intervertebral compression existed between L1/L2 [-2.54 mm] and L5/S1 [-11.84 mm], and between L3/L4 [-2.78 mm] and L5/S1 [-11.84 mm] [p <.05]. In closed chain APT, significant differences in relative intervertebral decompression existed between spinal levels L1/L2 [2.87mm] and L5/S1[24.48 mm] and between L3/L4 [2.94 mm] and L5/S1 [24.48 mm] [p <.05]. In open chain APT, significant differences in relative intervertebral decompression existed between spinal levels L4/L5 [1.53mm] and L5/S1 [25.14 mm] and between L2/L3 [1.68 mm] and L5/S1 [25.14 mm] [p<.05 for both]. Displacement during closed chain PPT was significantly greater than during open chain PPT, whereas APT showed no significant differences.

In PPT, open chain pelvic tilts did not produce as much lumbar intervertebral displacement compared to closed chain. In contrast, APT saw no significant differences between open and closed chain. Additionally, results illustrate the increase in lumbar lordosis during APT and the loss of lordosis during PPT.

The principal of “function priority, early rehabilitation, and return to sports” is now the goal for sports injury rehabilitation. Neuromuscular electrical stimulation for anterior cruciate ligament (ACL) reconstruction is a rising procedure for early rehabilitation. This paper systematically assessed the effects of neuromuscular electrical stimulation on postoperative ACL reconstruction to provide guidance for physiotherapist and patient when designing a suitable rehabilitation protocol.

To evaluate the interventional outcomes of neuromuscular electrical stimulation following ACL reconstruction, we searched PubMed, EMbase, the Cochrane Library, Web of Science and CNKI to collect all randomized controlled trials (RCTs) comparing the effects with neuromuscular electrical stimulation and without intervention on rehabilitation after ACL reconstruction up to January 30, 2022. Two investigators independently performed literature screening, data extraction, bias assessment of risk, and used RevMan 5.3 software to conduct a meta-analysis.

A total of six RCTs were included, and the results showed that the use of neuromuscular electrical stimulation after anterior cruciate ligament reconstruction significantly improved the International Knee Documentation Committee (IKDC) scores (MD 6.33, 95% CI [-0.43, 12.22]; I2 = 66%; p = 0.040), the Lysholm score (MD 7.94, 95% CI [6.49, 9.39]; I2 = 89%; p < 0.001), and the range of motion (ROM) (MD 9.99, 95% CI [7.97, 12.02]; I2 = 81%; p < 0.001) in the knees when compared to the control group without using neuromuscular electrical stimulation.

Existing evidence show that neuromuscular electrical stimulation is beneficial for early rehabilitation after ACL reconstruction. The use of neuromuscular electrical stimulation is encouraged in the design of rehabilitation protocol. However, due to the limited number of RCT studies and the small sample size, further multi-center RCTs with more participants are needed for a higher-level evidence.

Reduction of length of stay (LOS) without compromising quality of care is a trend observed in orthopaedic departments. To achieve this goal the pathway needs to be optimised. This requires team work than can be supported by e-health solutions. The objective of this study was to assess the impact of reduction in LOS on complications and readmissions in one hospital where accelerated discharge was introduced due to the pandemic.

317 patients with primary total hip and total knee replacements treated in the same hospital between October 2018 and February 2021 were included. The patients were divided in two groups: the pre-pandemic group and the pandemic group. The discharge criteria were: patient feels comfortable with going back home, patient has enough support at home, no wound leakage, and independence in activities of daily living. No face-to-face surgeon or nurse follow-up was planned. Patients’ progress was monitored via the mobile application. The patients received information, education materials, postoperative exercises and a coaching via secure chat. The length of stay (LOS) and complications were assessed through questions in the app and patients filled in standard PROMs preoperatively, at 6 weeks and 3 months.

Before the pandemic, 64.8% of the patients spent 3 nights at hospital, whereas during the pandemic, 52.0% spent only 1 night. The median value changed from 3 days to 1 day. The complication rate before the pandemic of 15% dropped to 9 % during the pandemic. The readmission rate remained stable with 4% before the pandemic and 5 % during the pandemic. No difference were observed for PROMS between groups.

The results of this study showed that after a hip and knee surgery, the shortening of the LOS from three to one night resulted in less complications and a stable rate of readmissions. These results are in line with literature data on enhanced recovery after hip and knee arthroplasty.

The reduction of LOS for elective knee and hip arthroplasty during the pandemic period proved safe. The concept used in this study is transferable to other hospitals, and may have economic implications through reduced hospital costs.

Open tibial fractures can be difficult to manage, with a range of factors that could affect treatment and outcome. We present a large cohort of patients, and analyse which factors have significant associations with infection outcome. Elucidation will allow clinicians to strive for treatment optimisation, and patients to be advised on likely complications

Open tibia fractures treated at a major trauma centre between 2015-2021 were included. Mean age at injury was 55.4 (range 13-102). Infection status was categorized into no infection, superficial infection, and osteomyelitis.

Age, mode of injury, polytrauma, fibula status, Gustilo-Anderson (GA) classification, wound contamination, time from injury to: first procedure/definitive plastics procedure/definitive fixation, type of definitive fixation, smoking and diabetic status, and BMI, were collected. Multicollinearity was calculated, with highly correlated factors removed. Multinomial logistic regression was performed. Chi Squared testing, with Post Hoc Bonferroni correction was performed for complex categorical factors.

Two hundred forty-four patients with open tibial fractures were included. Forty-five developed superficial infection (18.4%), and thirty-nine developed osteomyelitis (16.0%).

Polytrauma, fibula status, and type of definitive fixation were excluded from the multivariate model due to strong multicollinearity with other variables.

With reference to the non-infected outcome; superficial infection patients had higher BMI (p<0.01), higher GA grade (p<0.01), osteomyelitis patients had longer time to definitive fixation (p=0.049) and time to definitive plastics procedure (p=0.013), higher GA grade (p<0.01), and positive wound contamination(p=0.015).

Poc hoc analysis showed “no infection” was positively associated with GA-I (p=0.029) and GA-II (p<0.01), and negatively associated with GA-IIIC (p<0.01). Osteomyelitis was positively associated with GA-IIIc (p<0.01)

This study investigated the associations between the injury and presentation factors that may affect infection outcome. The variables highlighted are the factors clinicians should give extra consideration to when treating cases, and take preventative measures to optimize treatment and mitigate infection risk.

Infections in spine surgery are relatively common and devastating complications, a significant burden to the patient and the healthcare system. Usually, the treatment of SSIs consists of aggressive and prolonged antibiotic therapy, multiple debridements, and in chronic cases, hardware removal. Infections are correlated with worse subjective outcomes and even higher mortality.

Depending on the type of spine surgery, the infection rate has been reported to be as higher as 20%. Recently silver-coated implants have been introduced in spine surgery to reduce the incidence of post-operative infections and to improve implant survivorship.

The aim of the present study is to evaluate complications and outcomes in patients treated with silver-coated implants because of spine infection.

All consecutive patients who had spine stabilization with a silver-coated implant from 2018 to 2021 were screened for inclusion in the study. Inclusion criteria were: (1) six months of minimum follow-up; (2) previous surgical site infection; hematogenous spondylodiscitis requiring surgical stabilization. Demographic and surgical information were obtained via chart review, all the device-related complications and the reoperation rate were also reported.

A total of 57 patients were included in the present study. The mean age was 63.4 years, and there were 36 (63%) males and 21 (37%) females. Among the included cases, 57% were SSIs, 33% were spondylodiscitis, and 9% were hardware mobilization.

Comorbidities such as diabetes mellitus, obesity, smoke, and oncological history were significant risk factors. In addition, the organisms cultured were Staphylococcus species in most of the cases. At six months of follow-up, 40% of patients were considered free from infection, while 20% needed multiple surgeries.

The present research showed satisfactory results of silver-coated implants for the treatment of spine infection.

Proximal humeral shaft fractures are commonly treated with long straight locking plates endangering the radial nerve distally. The aim of this study was to investigate the biomechanical competence in a human cadaveric bone model of 90°-helical PHILOS plates versus conventional straight PHILOS plates in proximal third comminuted humeral shaft fractures.

Eight pairs of humeral cadaveric humeri were instrumented using either a long 90°-helical plate (group1) or a straight long PHILOS plate (group2). An unstable proximal humeral shaft fracture was simulated by means of an osteotomy maintaining a gap of 5cm. All specimens were tested under quasi-static loading in axial compression, internal and external rotation as well as bending in 4 directions. Subsequently, progressively increasing internal rotational loading until failure was applied and interfragmentary movements were monitored by means of optical motion tracking.

Flexion/extension deformation (°) in group1 was (2.00±1.77) and (0.88±1.12) in group2, p=0.003. Varus/valgus deformation (°) was (6.14±1.58) in group1 and (6.16±0.73) in group2, p=0.976. Shear (mm) and displacement (°) under torsional load were (1.40±0.63 and 8.96±0.46) in group1 and (1.12±0.61 and 9.02±0.48) in group2, p≥0.390. However, during cyclic testing shear and torsional displacements and torsion were both significantly higher in group 1, p≤0.038. Cycles to catastrophic failure were (9960±1967) in group1 and (9234±1566) in group2, p=0.24.

Although 90°-helical plating was associated with improved resistance against varus/valgus deformation, it demonstrated lower resistance to flexion/extension and internal rotation as well as higher flexion/extension, torsional and shear movements compared to straight plates. From a biomechanical perspective, 90°-helical plates performed inferior compared to straight plates and alternative helical plate designs with lower twist should be investigated in future paired cadaveric studies.

This study aims to investigate the mechanical properties of a rotator cuff tear repaired with a polypropylene interposition graft in an ovine infraspinatus ex-vivo model.

Twenty fresh shoulders from skeletally mature sheep were used in this study. A tear size of 20 mm from the tendon joint was created in the infraspinatus tendon to simulate a large tear in fifteen specimens. This was repaired with a polypropylene mesh used as an interposition graft between the ends of the tendon. Eight specimens were secured with mattress stitches while seven were secured to the remnant tendon on the greater tuberosity side by continuous stitching. Remaining five specimens with an intact tendon served as a control group. All specimens underwent cyclic loading with a universal testing machine to determine the ultimate failure load and gap distance.

Gap distance increased with progressive cyclic loading through 3000 cycles for all repaired specimens. Mean gap distance after 3000 cycles for both continuous and mattress groups are 1.7 mm and 4.2 mm respectively (P = .001). Significantly higher mean ultimate failure load was also observed with 549.2 N in the continuous group, 426.6 N in the mattress group and 370 N in the intact group.

The use of a polypropylene mesh as an interposition graft for large irreparable rotator cuff tears is biomechanically suitable and results in a robust repair that is comparable to an intact rotator cuff tendon. When paired with a continuous suturing technique, it demonstrates significantly resultant superior biomechanical properties that may potentially reduce re-tear rates after repairing large or massive rotator cuff tears.

The purpose of this study is to enhance massive bone allografts osseointegration used to reconstruct large bone defects. These allografts show >50% complication rate requiring surgical revision in 20% cases. A new protocol for total bone decellularisation exploiting the vasculature can offer a reduction of postoperative complication by annihilating immune response and improving cellular colonization/ osseointegration.

The nutrient artery of 18 porcine bones - humerus/femur/radius/ulna - was cannulated. The decellularization process involved immersion and sequential perfusion with specific solvents over a course of one week. Perfusion was realized by a peristaltic pump (mean flow rate: 6ml/min). The benefit of arterial perfusion was compared to a control group kept in immersion baths without perfusion.

Bone samples were processed for histology (HE, Masson's trichrome and DAPI for cell detection), immunohistochemistry (IHC : Collagen IV/elastin for intraosseous vascular system evaluation, Swine Leukocyte Antigen – SLA for immunogenicity in addition to cellular clearance) and DNA quantification. Sterility and solvent residues in the graft were also evaluated with thioglycolate test and pH test respectively.

Compared to native bones, no cells could be detected and residual DNA was <50ng/mg dry weight. Intramedullary spaces were completely cleaned. IHC showed the preservation of intracortical vasculature with channels bounded by Collagen IV and elastin within Haversian systems. IHC also showed a significant decrease in SLA signaling. All grafts were sterile at the last decellularization step and showed no solvent residue. The control group kept in immersion baths, paired with 6 perfused radii/ulnae, showed that the perfusion is mandatory to ensure complete decellularisation.

Our results prove the effectiveness of a new concept of total bone decellularisation by perfusion. These promising results could lead to a new technique of Vascularized Composite Allograft transposable to pre-clinical and clinical models.

The in vitro mimicking of bone microenvironment for the study of pathologies is a challenging field that requires the design of scaffolds with suitable morphological, structural and cytocompatible properties. During last years, 3D in vitro tumour models have been developed to reproduce mechanical, biochemical and structural bone microenvironment elements, allowing cells to behave as in vivo.

In this work, gas foamed polyether urethane foams (PUF) and 3D printed thermoplastic polyether urethane (3DP-PU) designed with different patterns are proposed as scaffolds for in vitro model of bone tissue. Surface coatings for a biomimetic behaviour of the 3D scaffold models were also investigated. Morphological, chemico-physical, mechanical properties, and biological in vitro behaviour were investigated.

PUFs for metastases investigation. The suitability of PUF as 3D in vitro model to study the interactions between bone tumour initiating cells and the bone microenvironment was investigated. PUF open porosity (>70%) appeared suitable to mimic trabecular bone structure. Human adipose derived stem cells (ADSC) were cultured and differentiated into osteoblast lineage on the PU foam, as confirmed by Alizarin Red staining and RT-PCR, thus offering a bone biomimetic microenvironment to the further co-culture with bone derived tumour-initiating cells (MCFS). Tumour aggregates were observed after three weeks of co-culture by e-cadherin staining and SEM; modification in CaP distribution was identified by SEM-EDX and associated to the presence of tumour cells.

3DP-PU as tumour bone model. 3D printed scaffolds have pores with a precise and regular geometry (0°-90°, 0°-45°-90°-135°, 0°-60°-120°). PU scaffold porosity evidenced values from 55 to 67%, values that belong to the porosity range of the trabecular bone tissue (30-90%). The compressive modulus varied between 2 and 4 MPa, depending on the printed pattern. Biomimetic nanostructured coating was performed on 0-90° 3DP-PU by Ionized Jet Deposition. Coatings had a submicrometric thickness, variable tuning deposition time, nanostructured surface morphology and biomimetic composition. Coating on 3DP-PU promoted cells colonization of the whole porous scaffolds, compared to the controls, where cells concentrated mostly on the outer layers.

In conclusion, based on the obtained results, scaffolds with different geometries have been successfully produced. Morphological and structural properties of the scaffolds here presented are suitable for mimicking the bone tissue, in order to produce a 3D in vitro model useful for bone pathologies research.

Recent studies on animal models focused on the effect of preserving tendon remnant of rotator cuff on tendon healing. A positive effect by combining tendon remnant preservation and small bone vents on the greater tuberosity in comparison with standard tendon-to-bone repair has been shown. The purpose of the present clinical study was to evaluate the efficacy of biologic augmentation of arthroscopic rotator cuff repair by maintaining tendon remnant on rotator cuff footprint combined with small bone vents of the greater tuberosity.

A retrospective study was conducted. All patients who underwent arthroscopic rotator cuff repair associated with small bone vents (nanofractures) and tendon footprint preservation were considered eligible for the study. Inclusion criteria were: diagnosis of full-thickness rotator cuff tear as diagnosed at preoperative magnetic resonance imaging (MRI) and confirmed at the time of surgery; minimum 24-month of follow-up and availability of post-operative MRI performed not earlier than 6 months after surgery. Exclusion criteria were: partial thickness tears, irreparable tears, capsulo-labral pathologies, calcific tendonitis, gleno-humeral osteoarthritis and/or previous surgery.

Primary outcome was the ASES score. Secondary outcomes were: Quick-DASH and WORC scores, and structural integrity of repaired tendons by magnetic resonance imaging (MRI) performed six months after surgery. A paired t-test was used to compare pre- and postoperative clinical outcomes. Subgroup analysis was performed according to tear size. Significance was set at p < 0.05.

The study included 29 patients (M:F = 15:14). Mean age (+ SD) of patients was 61.7 + 8.9 years. Mean follow-up was 27.4 ± 2.3 months. Comparison between pre- and postoperative functional scores showed significant clinical improvement (p < 0.001). Subgroup analysis for tear size showed significant differences in the QuickDASH score (0.04). Particularly, a significant difference in the QuickDASH score could be detected between medium and large tears (p=0.008) as well as medium and massive lesions (p=0.04). No differences could be detected between large and massive tears (p= 0.35). Postoperative imaging showed healed tendons in 21 out of 29 (72%) cases.

Preservation of tendon remnant combined with small bone vents in the repair of medium-to-massive full-thickness rotator cuff tears provided significant improvement in clinical outcome compared to baseline conditions with complete structural integrity in 72% of the cases.

Our knowledge of primary bone marrow edema (BME) of the knee is still limited. A major contributing factor is that it shares several radiological findings with a number of vascular, traumatic, and inflammatory conditions having different histopathological features and etiologies.

BME can be primary or secondary. The most commonly associated conditions are osteonecrosis, osteochondritis dissecans, complex regional pain syndrome, mechanical strain such as bone contusion/bruising, micro-fracture, stress fracture, osteoarthritis, and tumor. The etiology and pathogenesis of primary BME are unclear. Conservative treatment includes analgesics, non-steroidal anti-inflammatory drugs, weight-bearing limitations, physiotherapy, pulsed electromagnetic fields, prostacyclin, and bisphosphonates. Surgical treatment, with simple perforation, fragment stabilization, combined scraping and perforation, and eventually osteochondral or chondrocyte transplant, is reserved for the late stages. This retrospective study of a cohort of patients with primary BME of the knee was undertaken to describe their clinical and demographic characteristics, identify possible risk factors, and assess treatment outcomes.

We reviewed the records of 48 patients with primary BME of the knee diagnosed on MRI by two radiologists and two orthopedists. History, medications, pain type, leisure activities, smoking habits, allergies, and environmental factors were examined. Analysis of patients’ characteristics highlighted that slightly overweight middle-aged female smokers with a sedentary lifestyle are the typical patients with primary BME of the knee. In all patients, the chief symptom was intractable day and night pain (mean value, 8.5/10 on the numerical rating scale) with active as well as passive movement, regardless of BME extent. Half of the patients suffered from thyroid disorders; indeed, the probability of having a thyroid disorder was higher in our patients than in two unselected groups of patients, one referred to our orthopedic center (odds ratio, 18.5) and another suffering from no knee conditions (odds ratio, 9.8). Before pain onset, 56.3% of our cohort had experienced a stressful event (mourning, dismissal from work, concern related to the COVID-19 pandemic). After conservative treatment, despite the clinical improvement and edema resolution on MRI, 93.8% of patients described two new symptoms: a burning sensation in the region of the former edema and a reduced ipsilateral patellar reflex. These data suggest that even though the primary BME did resolve on MRI, the knee did not achieve full healing.

Rotator cuff repair has excellent clinical outcomes but continues to be a challenge when it comes to large and massive tears as well as revision procedures. Reported symptomatic retear rates are still too high to be acceptable. The purpose of the present study was to evaluate the effectiveness of a combination of augmentation techniques consisting of microfractures of the greater tuberosity, extracellular matrix (ECM) patch graft and subsequent platelet concentrate (PC) subacromial injections in revision rotator cuff repair.

The study was designed as a retrospective comparative study on prospectively collected data from a consecutive cohort of patients. All patients who underwent arthroscopic revision rotator cuff repair for symptomatic failure of previous posterosuperior rotator cuff repair were considered eligible for the study. Symptomatic failure had been diagnosed according to clinical examination and confirmed by magnetic resonance imaging (MRI). Structural integrity had been assessed on MRI and classified according to Sugaya classification. Only patients affected by stage IV-V were considered eligible. Tear reparability was confirmed during arthroscopy. Only patients with a minimum 2 years follow-up were included. Patients were divided in two groups. In group 1 (control group) a standard arthroscopic revision and microfractures of the greater tuberosity were performed; in group 2 (experimental group), microfractures of the greater tuberosity and a ECM patch graft were used to enhance tendon repair, followed by postoperative PC injections. Minimum follow-up was 12 months. Primary outcome was the Constant-Murley score (CMS) normalized for age and gender. Subjective outcome was assessed with the Disabilities of the Arm, Shoulder and Hand (DASH) score in its short version (Quick-DASH). Tendon integrity was assessed with MRI at 6 months after surgery. Comparison between groups for all discrete variables at baseline and at follow-up was carried out with the Student's t-test for normally distributed data, otherwise Mann-Whitney U-test was used. Within-group differences (baseline vs follow-up) for discrete variables were analyzed by paired t-test, or by Wilcoxon signed-rank test in case of data with non-normal distribution. Differences for categorical variables were assessed by chi-squared test. Significance was considered for p values < 0.05.

Forty patients were included in the study (20 patients for each group). The mean follow-up was 13 ± 1.6 months. No patients were lost at the follow up. Comparison between groups did not show significant differences for baseline characteristics. At follow-up, mean CMS was 80.7 ± 16.6 points in group 1 and 91.5 ± 11.5 points in group 2 (p= 0.022). Mean DASH score was 28.6 ± 21.6 points in group 1 and 20.1 ± 17.4 points in group 2 (p= 0.178). Post-operative MRI showed 6 healed shoulders in Group 1 and 16 healed shoulders in Group 2 (p<0.004). No postoperative complications were reported in both groups.

The combination of microfractures of the greater tuberosity, ECM patch graft, and subsequent PC subacromial injections is an effective strategy in improving tendon healing rate.

Bone metastases radiographically appear as regions with high (i.e. blastic metastases) or low (i.e. lytic metastases) bone mineral density. The clinical assessment of metastatic features is based on computed tomography (CT) but it is still unclear if the actual size of the metastases can be accurately detected from the CT images and if the microstructure in regions surrounding the metastases is altered (Nägele et al., 2004, Calc Tiss Int). This study aims to evaluate (i) the capability of the CT in evaluating the metastases size and (ii) if metastases affect the bone microstructure around them.

Ten spine segments consisted of a vertebra with lytic or mixed metastases and an adjacent control (radiologically healthy) were obtained through an ethically approved donation program. The specimens were scanned with a clinical CT (AquilionOne, Toshiba: slice thickness:1mm, in-plane resolution:0.45mm) to assess clinical metastatic features and a micro-CT (VivaCT80, Scanco, isotropic voxel size:0.039mm) to evaluate the detailed microstructure. The volume of the metastases was measured from both CT and micro-CT images (Palanca et al., 2021, Bone) and compared with a linear regression. The microstructural alteration around the metastases was evaluated in the volume of interest (VOI) defined in the micro-CT images as the volume of the vertebral body excluding the metastases. Three 3D microstructural parameters were calculated in the VOI (CTAn, Bruker SkyScan): Bone Volume Fraction (BV/TV), Trabecular Thickness (Tb.Th.), Trabecular Spacing (Tb.Sp.). Medians of each parameter were compared (Kruskal-Wallis, p=0.05).

One specimen was excluded as it was not possible to define the size of the metastases in the CT scans. A strong correlation between the volume obtained from the CT and micro-CT images was found (R2=0.91, Slope=0.97, Intercept=2.55, RMSE=5.7%, MaxError=13.12%). The differences in BV/TV, Tb.Th. and Tb.Sp. among vertebrae with lytic and mixed metastases and control vertebrae were not statistically significant (p-value>0.6). Similar median values of BV/TV were found in vertebrae with lytic (13.2±2.4%) and mixed (12.8±9.8%) metastases, and in controls (13.0±10.1%). The median Tb.Th. was 176±18 ∓m, 179±43 ∓m and 167±91 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. The median Tb. Sp. was 846±26 ∓m, 849±286 ∓m and 880±116 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively.

In conclusion, the size of vertebral metastases can be accurately assess using CT images. The 3D microstructural parameters measured were comparable with those reported in the literature for healthy vertebrae (Nägele et al., 2004, Calc Tiss Int, Sone et al., 2004, Bone) and showed how the microstructure of the bone tissue surrounding the lesion is not altered by the metastases.

Breast cancer is the most frequent malignancy in women with an estimation of 2.1 million new diagnoses in 2018. Even though primary tumours are usually efficiently removed by surgery, 20–40% of patients will develop metastases in distant organs. Bone is one of the most frequent site of metastases from advanced breast cancer, accounting from 55 to 58% of all metastases. Currently, none of the therapeutic strategies used to manage breast cancer bone metastasis are really curative. Tailoring a suitable model to study and evaluate the disease pathophysiology and novel advanced therapies is one of the major challenges that will predict more effectively and efficiently the clinical response. Preclinical traditional models have been largely used as they can provide standardization and simplicity, moreover, further advancements have been made with 3D cultures, by spheroids and artificial matrices, patient derived xenografts and microfluidics. Despite these models recapitulate numerous aspects of tumour complexity, they do not completely mimic the clinical native microenvironment. Thus, to fulfil this need, in our study we developed a new, advanced and alternative model of human breast cancer bone metastasis as potential biologic assay for cancer research. The study involved breast cancer bone metastasis samples obtained from three female patients undergoing wide spinal decompression and stabilization through a posterior approach. Samples were cultured in a TubeSpin Bioreactor on a rolling apparatus under hypoxic conditions at time 0 and for up to 40 days and evaluated for viability by the Alamar Blue test, gene expression profile, histology and immunohistochemistry. Results showed the maintenance and preservation, at time 0 and after 40 days of culture, of the tissue viability, biological activity, as well as molecular markers, i.e. several key genes involved in the complex interactions between the tumour cells and bone able to drive cancer progression, cancer aggressiveness and metastasis to bone. A good tis sue morphological and microarchitectural preservation with the presence of lacunar osteolysis, fragmented trabeculae locally surrounded by osteoclast cells and malignant cells and an intense infiltration by tumour cells in bone marrow compartment in all examined samples. Histomorphometrical data on the levels of bone resorption and bone apposition parameters remained constant between T0 and T40 for all analysed patients. Additionally, immunohistochemistry showed homogeneous expression and location of CDH1, CDH2, KRT8, KRT18, Ki67, CASP3, ESR1, CD8 and CD68 between T0 and T40, thus further confirming the invasive behaviour of breast cancer cells and indicating the maintaining of the metastatic microenvironment. The novel tissue culture, set-up in this study, has significant advantages in comparison to the pre-existent 3D models: the tumour environment is the same of the clinical scenario, including all cell types as well as the native extracellular matrix; it can be quickly set-up employing only small samples of breast cancer bone metastasis tissue in a simple, ethically correct and cost-effective manner; it bypasses and/or decreases the necessity to use more complex preclinical model, thus reducing the ethical burden following the guiding principles aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes; it can allow the study of the interactions within the breast cancer bone metastasis tissue over a relatively long period of up to 40 days, preserving the tumour morphology and architecture and allowing also the evaluation of different biological factors, parameters and activities. Therefore, the study provides for the first time the feasibility and rationale for the use of a human-derived advanced alternative model for cancer research and testing of drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses.

Vertebral metastases are the most common type of malignant lesions of the spine. Although this tumour is still considered incurable and standard treatments are mainly palliative, the standard approach consists in surgical resection, which results in the formation of bone gaps. Hence, scaffolds, cements and/or implants are needed to fill the bone lacunae.

Here, we propose a novel approach to address spinal metastases recurrence, based on the use of anti-tumour metallic-based nanostructured coatings. Moreover, for the first time, a gradient microfluidic approach is proposed for the screening of nanostructured coatings having anti-tumoral effect, to determine the optimal concentration of the metallic compound that permits selective toxicity towards tumoral cells.

Coatings are based on Zinc as anti-tumour agent, which had been never explored before for treatment of bone metastases.

The customized gradient generating microfluidic chip was designed by Autodesk Inventor and fabricated from a microstructured mould by using replica moulding technique. Microstructured mould were obtained by micro-milling technique. The chip is composed of a system of microfluidic channels generating a gradient of 6 concentrations of drug and a compartment with multiple arrays of cell culture chambers, one for each drug concentration. The device is suitable for dynamic cultures and in-chip biological assays. The formation of a gradient was validated using a methylene blue solution and the cell loading was successful.

Preliminary biological data on 3D dynamic cultures of stromal cells (bone-marrow mesenchymal stem cells) and breast carcinoma cells (MDA-MB-231) were performed in a commercial microfluidic device.

Results showed that Zn eluates had a selective cytotoxic effect for tumoral cells. Indeed, cell migration and cell replication of treated tumoral cells was inhibited. Moreover, the three-dimensionality of the model strongly affected the efficacy of Zn eluates, as 2D preliminary experiments showed a high cytotoxic effect of Zn also for stromal cells, thus confirming that traditional screening tests on 2D cultured cells usually lead to an overestimation of drug efficacy and toxicity.

Based on preliminary data, the customized platform could be considered a major advancement in cancer drug screenings as it also allows the rapid and efficient screening of biomaterials having antitumor effect.

Prosthetic joint infections represent complications connected to the implantation of biomedical devices. Bacterial biofilm is one of the main issues causing infections from contaminated orthopaedic prostheses. Biofilm is a structured community of microbial cells that are firmly attached to a surface and have unique metabolic and physiological attributes that induce improved resistance to environmental stresses including toxic compounds like antimicrobial molecules (e.g. antibiotics). Therefore, there is increasing need to develop methods/treatments exerting antibacterial activities not only against planktonic (suspended) cells but also against adherent cells of pathogenic microorganisms forming biofilms. In this context, metal-based coatings with antibacterial activities have been widely investigated and used in the clinical practice. However, traditional coatings exhibit some drawbacks related to the insufficient adhesion to the substrate, scarce uniformity and scarce control over the toxic metal release reducing the biofilm formation prevention efficacy. Additionally, standardized and systematic approaches to test antibacterial activity of newly developed coatings are still missing, while standard microbiological tests (e.g. soft-agar assays) are typically used that are limited in terms of simultaneous conditions that can be tested, potentially leading to scarce reproducibility and reliability of the results.

In this work, we combined the Calgary Biofilm Device (CBD) as a device for high-throughput screening, together with a novel plasma-assisted technique named Ionized Jet Deposition (IJD), to generate and test new generation of nanostructured silver- and zinc-based films as coatings for biomedical devices with antibacterial and antibiofilm properties. During the experiments we tested both planktonic and biofilm growth of four bacterial strains, two gram-positive and two gram-negative bacterial strains, i.e. Staphylococcus aureus ATCC 6538P, Enterococcus faecalis DP1122 and Escherichia coli ATCC 8739 and Pseudomonas aeruginosa PAO1, respectively. The use of CBD that had the only wells covered with the metal coatings while the biofilm supports (pegs) were not sheltered allowed to selectively define the toxic effect of the metal release (from the coating) against biofilm development in addition to the toxic activity exerted by contact killing mechanism (on biofilms formed on the coating). The results indicated that the antibacterial and antibiofilm effects of the metal coatings was at least partly gram staining dependent. Indeed, Gram negative bacterial strains showed high sensitivity toward silver in both planktonic growth and biofilm formation, whereas zinc coatings provided a significant inhibitory activity against Gram positive bacterial strains. Furthermore, the coatings showed the maximal activity against biofilms directly forming on them, although, Zn coating showed a strong effect against biofilms of gram-positive bacteria also formed on uncoated pegs.

We conclude that the metal-based coatings newly developed and screened in this work are efficient against bacterial growth and adherence opening possible future applications for orthopedic protheses manufacturing.

Open limb fractures are typically due to a high energy trauma. Several recent studied have showed treatment's superiority when a multidisciplinary approach is applied. World Health Organization reports that isolate limb traumas have an incidence rate of 11.5/100.000, causing high costs in terms of hospitalization and patient disability.

A lack of experience in soft tissue management in orthopaedics and traumatology seems to be the determining factor in the clinical worsening of complex cases. The therapeutic possibilities offered by microsurgery currently permit simultaneous reconstruction of multiple tissues including vessels and nerves, reducing the rate of amputations, recovery time and preventing postoperative complications.

Several scoring systems to assess complex limb traumas exist, among them: NISSSA, MESS, AO and Gustilo Anderson. In 2010, a further scoring system was introduced to focus open fractures of all locations: OTA-OFC. Rather than using a single composite score, the OTA-OFC comprises five components grades (skin, arterial, muscle, bone loss and contamination), each rated from mild to severe. The International Consensus Meeting of 2018 on musculoskeletal infections in orthopaedic surgery identified the OTA-OFC score as an efficient catalogue system with interobserver agreement that is comparable or superior to the Gustilo-Anderson classification. OTA-OFC predicts outcomes such as the need for adjuvant treatments or the likelihood of early amputation. An orthoplastic approach reconstruction must pay adequate attention to bone and soft tissue infections management. Concerning bone management: there is little to no difference in terms of infection rates for Gustilo-Anderson types I–II treated by reamed intramedullary nail, circular external fixator, or unreamed intramedullary nail. In Gustilo-Anderson IIIA-B fractures, circular external fixation appears to provide the lowest infection rates when compared to all other fixation methods.

Different technique can be used for the reconstruction of bone and soft tissue defects based on each clinical scenario. Open fracture management with fasciocutaneous or muscle flaps shows comparable outcomes in terms of bone healing, soft tissue coverage, acute infection and chronic osteomyelitis prevention. The type of flap should be tailored based on the type of the defect, bone or soft tissue, location, extension and depth of the defect, size of the osseous gap, fracture type, and orthopaedic implantation. Local flaps should be considered in low energy trauma, when skin and soft tissue is not traumatized. In high energy fractures with bone exposure, muscle flaps may offer a more reliable reconstruction with fewer flap failures and lower reoperation rates. On exposed fractures several studies report precise timing for a proper reconstruction. Hence, timing of soft tissue coverage is a critical for length of in-hospital stay and most of the early postoperative complications and outcomes. Early coverage has been associated with higher union rates and lower complications and infection rates compared to those reconstructed after 5-7 days. Furthermore, early reconstruction improves flap survival and reduces surgical complexity, as microsurgical free flap procedures become more challenging with a delay due to an increased pro-thrombotic environment, tissue edema and the increasingly friable vessels.

Only those patients presenting to facilities with an actual dedicated orthoplastic trauma service are likely to receive definitive treatment of a severe open fracture with tissue loss within the established parameters of good practice. We conclude that the surgeon's experience appears to be the decisive element in the orthoplastic approach, although reconstructive algorithms may assist in decisional and planification of surgery.

With the coronavirus disease 2019 (COVID-19) pandemic, remote working has been ubiquitously implemented to reduce disease transmission via minimization of in-person interactions. Low back pain (LBP) is the first cause of disability worldwide and is frequently reported by workers with sedentary occupations. This cross-sectional study aimed to assess the role of remote working in a population of adults affected by LBP through an online questionnaire.

We enrolled 136 teleworkers affected by LBP. A total of 101 responses were received and 93 suitable questionnaires were included in the final analysis. Demographic data, remote working features and tasks, and LBP burden were analysed. The psychological burden of remote working was evaluated with the World Health Organization Five Well-Being Index (WHO-5) and the Patient Health Questionnaire-2 (PHQ-2). LBP severity was evaluated using a visual analog scale (VAS). LBP-related disability was assessed using the Oswestry Disability Index (ODI). The effect of LBP on working capacity was examined with the Occupational Role Questionnaire (ORQ). Independent risk factors related to LBP worsening were identified using a multivariate logistic regression model.

LBP severity was significantly higher compared to previous in-person working (p<0.0001) as well as average weekly work hours (p<0.001). Furthermore, the risk of LBP deterioration was associated with being divorced (OR: 4.28, 95% CI: 1.27-14.47; p=0.019) or living with others (OR: 0.24, 95% CI: 0.07-0.81; p=0.021), higher ill-being (OR: 0.91, 95% CI: 0.83-0.99; p=0.035) and depression scores (OR: 1.38, 95% CI: 1.00-1.91; p=0.048), as well as having reported unchanged (OR: 0.22, 95% CI: 0.08-0.65; p=0.006) or decreased job satisfaction (OR: 0.16, 95% CI: 0.05-0.54; p=0.003) and increased stress levels (OR: 3.00, 95% CI: 1.04-8.65; p=0.042).

These findings highlight key factors to consider for improving remote workers’ physical and mental wellbeing and decrease their LBP burden.

Paediatric musculoskeletal (MSK) disorders often produce severe limb deformities, that may require surgical correction. This may be challenging, especially in case of multiplanar, multifocal and/or multilevel deformities. The increasing implementation of novel technologies, such as virtual surgical planning (VSP), computer aided surgical simulation (CASS) and 3D-printing is rapidly gaining traction for a range of surgical applications in paediatric orthopaedics, allowing for extreme personalization and accuracy of the correction, by also reducing operative times and complications. However, prompt availability and accessible costs of this technology remain a concern. Here, we report our experience using an in-hospital low-cost desk workstation for VSP and rapid prototyping in the field of paediatric orthopaedic surgery.

From April 2018 to September 2022 20 children presenting with congenital or post-traumatic deformities of the limbs requiring corrective osteotomies were included in the study. A conversion procedure was applied to transform the CT scan into a 3D model. The surgery was planned using the 3D generated model. The simulation consisted of a virtual process of correction of the alignment, rotation, lengthening of the bones and choosing the level, shape and direction of the osteotomies. We also simulated and calculated the size and position of hardware and customized massive allografts that were shaped in clean room at the hospital bone bank. Sterilizable 3D models and PSI were printed in high-temperature poly-lactic acid (HTPLA), using a low-cost 3D-printer.

Twenty-three operations in twenty patients were performed by using VSP and CASS. The sites of correction were: leg (9 cases) hip (5 cases) elbow/forearm (5 cases) foot (5 cases) The 3D printed sterilizable models were used in 21 cases while HTPLA-PSI were used in five cases. customized massive bone allografts were implanted in 4 cases. No complications related to the use of 3D printed models or cutting guides within the surgical field were observed. Post-operative good or excellent radiographic correction was achieved in 21 cases.

In conclusion, the application of VSP, CASS and 3D-printing technology can improve the surgical correction of complex limb deformities in children, helping the surgeon to identify the correct landmarks for the osteotomy, to achieve the desired degree of correction, accurately modelling and positioning hardware and bone grafts when required. The implementation of in-hospital low-cost desk workstations for VSP, CASS and 3D-Printing is an effective and cost-advantageous solution for facilitating the use of these technologies in daily clinical and surgical practice.

Adverse events (AEs) are still a major problem in spinal surgery, despite advances in surgical techniques, innovative technologies available and the introduction of checklist and predictive score systems aimed at reducing surgical complications.

We previously analysed the results of the introduction of the WHO Safety Surgical Checklist (SSC) in our Institution, comparing the incidence of complications between two periods: from January to December 2010 (without checklist) and from January 2011 and December 2012 (with checklist), in order to assess the checklist effectiveness.

The sample size was 917 patients with an average of 30 months of follow-up. Complications were observed in 107 patients (11.6%) among 917 spinal surgery procedures performed, with 159 (17.3%) complications in total. The overall incidence of complications for trauma, infectious pathology, oncology, and degenerative disease was 22.2%, 19.2%, 18.4%, and 15.3%, respectively. We observed a reduction of the overall incidence of complications following the introduction of the WHO Surgical Checklist: in 2010 without checklist, the incidence of complications was 24.2%, while in 2011 and 2012, following the checklist introduction, the incidence of complications was 16.7% and 11.7%, respectively (mean 14.2%) (p<0.0005).

Thus, the SSC appeared to be an effective tool to reduce complications in spinal surgery and we proposed to extend the use of checklist system also to the pre-operative and post-operative phases in order to further reduce the incidence of complications.

We also believe that a correct capture and classification of complications is fundamental to generate a clinical decision support system aimed at improving patients’ safety in spinal surgery.

In the period between January 2017 and January 2018 we prospectively recorded the adverse events and complications of patients undergoing spinal surgery in our department, without using any collection system. Then we retrospectively recorded the intraoperative and postoperative adverse events of surgically treated patients during the same one-year period, using the SAVES v2 system introduced by Rampersaud and collaborators (Rampersaud YR et al. J Neurosurg Spine 2016 Aug; 25 (2): 256-63) to classify them.

In the one-year period from January 2017 to January 2018 a total of 336 patients underwent spinal surgery: 223 for degenerative conditions and 113 for spinal tumors. Comorbidities were collected (Charlson Comorbidity Index [CCI]).

Overall, a higher number of adverse events (AEs) was recorded using SAVES compared to the prospective recording without the use of any capture system and the increased number was statistically significant for early postoperative AEs (138/336 vs 44/336, p<0.001).

210 adverse events were retrospectively recorded using the SAVES system (30 intraoperative adverse events, 138 early postoperative and 42 late postoperative adverse events). 99 patients (29.5%) on the cohort had at least one complication.

Furthermore, the correlation between some risk factors and the onset of complications or the prolonged length of stay was statistically analyzed. The risk factors taken into account were: age, presence of comorbidities (CCI), ASA score, previous surgery at the same level, type of intervention, location of the disease, duration of the surgery.

In particular, the duration of the surgery (more than 3 hours) and the presence of previous surgeries resulted to be risk factors for complications in multivariate analyses

Infection in orthopedics is a challenge, since it has high incidence (rates can be up to 15-20%, also depending on the surgical procedure and on comorbidities), interferes with osseointegration and brings severe complications to the patients and high societal burden. In particular, infection rates are high in oncologic surgery, when biomedical devices are used to fill bone gaps created to remove tumors. To increase osseointegration, calcium phosphates coatings are used. To prevent infection, metal- and mainly silver-based coatings are the most diffused option. However, traditional techniques present some drawbacks, including scarce adhesion to the substrate, detachments, and/or poor control over metal ions release, all leading to cytotoxicity and/or interfering with osteointegration. Since important cross-relations exist among infection, osseointegration and tumors, solutions capable of addressing all would be a breakthrough innovation in the field and could improve clinical practice.

Here, for the first time, we propose the use antimicrobial silver-based nanostructured thin films to simultaneously discourage infection and bone metastases. Coatings are obtained by Ionized Jet Deposition, a plasma-assisted technique that permits to manufacture films of submicrometric thickness having a nanostructured surface texture. These characteristics, in turn, allow tuning silver release and avoid delamination, thus preventing toxicity. In addition, to mitigate interference with osseointegration, here silver composites with bone apatite are explored. Indeed, capability of bone apatite coatings to promote osseointegration had been previously demonstrated in vitro and in vivo. Here, antibacterial efficacy and biocompatibility of silver-based films are tested in vitro and in vivo. Finally, for the first time, a proof-of-concept of antitumor efficacy of the silver-based films is shown in vitro.

Coatings are obtained by silver and silver-bone apatite composite targets. Both standard and custom-made (porous) vertebral titanium alloy prostheses are used as substrates.

Films composition and morphology depending on the deposition parameters are investigated and optimized. Antibacterial efficacy of silver films is tested in vitro against gram+ and gram- species (E. coli, P. aeruginosa, S. aureus, E. faecalis), to determine the optimal coatings characteristics, by assessing reduction of bacterial viability, adhesion to substrate and biofilm formation. Biocompatibility is tested in vitro on fibroblasts and MSCs and, in vivo on rat models. Efficacy is also tested in an in vivo rabbit model, using a multidrug resistant strain of S. aureus (MRSA, S. aureus USA 300). Absence of nanotoxicity is assessed in vivo by measuring possible presence of Ag in the blood or in target organs (ICP-MS). Then, possible antitumor effect of the films is preliminary assessed in vitro using MDA-MB-231 cells, live/dead assay and scanning electron microscopy (FEG-SEM). Statistical analysis is performed and data are reported as Mean ± standard Deviation at a significance level of p <0.05. Silver and silver-bone apatite films show high efficacy in vitro against all the tested strains (complete inhibition of planktonic growth, reduction of biofilm formation > 50%), without causing cytotoxicity. Biocompatibility is also confirmed in vivo.

In vivo, Ag and Ag-bone apatite films can inhibit the MRSA strain (>99% and >86% reduction against ctr, respectively). Residual antibacterial activity is retained after explant (at 1 month). These studies indicate that IJD films are highly tunable and can be a promising route to overcome the main challenges in orthopedic prostheses.

In the context of regenerative medicine for the treatment of musculoskeletal pathologies mesenchymal stromal cells (MSCs) have shown good results thanks to secretion of therapeutic factors, both free and conveyed within the extracellular vesicles (EV), which in their totality constitute the “secretome”. The portfolio and biological activity of these molecules can be modulated by both in vitro and in vivo conditions, thus making the analysis of these activities very complex. A deep knowledge of the targets regulated by the secretome has become a matter of fundamental importance and a homogeneous and complete molecular characterization is still lacking in the field of applications for the musculoskeletal system. Therefore, the aim of this work was to characterize the secretome obtained from adipose-derived MSCs (ASCs), and its modulation after pre-conditioning of the ASCs. Pre-conditioning was done by culturing cells in the presence of i) high levels of IFNγ, as proposed for the production of clinical grade secretome with enhanced regenerative potential, ii) low levels of inflammatory stimuli, mimicking conditions found in the osteoarthritis (OA) synovial fluid. Furthermore, EVs ability to migrate within cartilage, chondrocyte and synoviocytes obtained from OA patients was evaluated.

The data showed that more than 50 cytokines / chemokines and more than 200 EV-microRNAs are detectable at various intensity levels in ASCs secretomes. The majority of the most abundantly present molecules are involved in the remodelling of the extracellular matrix and in the homeostasis and chemotaxis of inflammatory cells including macrophages, which in OA are often characterized by an M1 inflammatory polarization, promoting their transition to an M2 anti-inflammatory phenotype. Inflammatory priming with IFNγ and synovial fluid-like conditions were able to further increase the ability of the secretome to interact with inflammatory cells and modulate their migration. Finally, the penetration of the EVs in the cartilage explants resulted a rapid process, which begins a few minutes after administration of the EVs that are able to reach a depth of 30-40 μm in 5 hours. The same capacity for interaction was also verified in chondrocytes and synoviocytes isolated from the cartilage and synovial membrane of OA patients.

Thanks to the soluble factors and EV-microRNAs, the ASCs secretome has shown a strong propensity to modulate the inflammatory and degenerative processes that characterize OA. The inflammatory pre-conditioning through high concentrations of inflammatory molecules or in conditions similar to the synovial fluid of OA patients was able to increase this capacity by increasing their chemotactic power. The microscopy data also support the hypothesis of the ability of MSC-EVs to influence the chondrocytes residing in the ECM of the cartilage and the synovial cells of the synovial membrane through active interaction and the release of their therapeutic content.

Favoring osseointegration and avoiding bacterial contamination are the key challenges in the design of implantable devices for orthopedic applications. To meet these goals, a promising route is to tune the biointerface of the devices, that can regulate interactions with the host cells and bacteria, by using nanostructured antibacterial and bioactive coatings. Indeed, the selection of adequate metal-based coatings permits to discourage infection while avoiding the development of bacterial resistance and nanostructuring permits to tune the release of the antimicrobial compounds, allowing high efficacy and decreasing possible cytotoxic effects. In addition, metal-doped calcium phosphates-based nanostructured coatings permit to tune both composition and morphology of the biointerfaces, allowing to regulate host cells and bacteria response. To tune the biointerfaces of implantable devices, nanostructured coatings can be used, but their use is challenging when the substrate is heat-sensitive and/or porous.

Here, we propose the use of Ionized Jet Deposition (IJD) to deposit metallic and ion-doped calcium phosphates materials onto different polymeric substrates, without heating and damaging the substrate morphology. 3D printed scaffolds in polylactic acid (PLA) and polyurethane (PU), and electrospun matrices in polycaprolactone (PCL) and PLA were used as substrates. Biogenic apatite (HA), ion doped (zinc, copper and iron) tricalcium phosphate (TCP) and silver (Ag) coatings were obtained on porous and custom-made polymeric substrates.

Chemical analyses confirmed that coatings composition matches that of the target materials, both in terms of main phase (HA or TCP) and ion doping (presence of Cu, Zn or Fe ion). Deposition parameters, and especially its duration time, influence the coating features (morphology and thickness) and substrate damage. Indeed, SEM/EDS observations show the presence of nanostructured agglomerates on substrates surface. The dimensions of the aggregates and the thickness of the coating films increase increasing the deposition time, without affecting the substrate morphology (no porosity alteration or fibers damaging). The possible substrate damage is influenced by target and substrate material, but it can be avoided modulating deposition time.

Once the parameters are optimized, the models show suitable in vitro biological efficacy for applications in bone models, regenerative medicine and infection. Indeed, HA-based coatings favor cells adhesion on printed and electrospun fibers. For antibacterial applications, the ion doped TCP coatings can reduce the bacterial growth and adhesion (E.coli and S.aureus) on electrospun matrices.

To conclude, it is possible achieve different properties applying nanostructured coatings with IJD technique on polymeric substrates, modulating deposition conditions to avoid substrate damage.

The anatomy of the femur shows a high inter-patient variability, making it challenging to design standard prosthetic devices that perfectly adapt to the geometry of each individual. Over the past decade, Statistical Shape Models (SSMs) have been largely used as a tool to represent an average shape of many three-dimensional objects, as well as their variation in shape. However, no studies of the morphology of the residual femoral canal in patients who have undergone an amputation have been performed. The aim of this study was therefore to evaluate the main modes of variation in the shape of the canal, therefore simulating and analysing different levels of osteotomy.

To assess the variability of the femoral canal, 72 CT-scans of the lower limb were selected. A segmentation was performed to isolate the region of interest (ROI), ranging from the lesser tip of the trochanter to the 75% of the length of the femur. The canals were then sized to scale, aligned, and 16 osteotomy levels were simulated, starting from a section corresponding to 25% of the ROI and up to the distal section. For each level, the main modes of variations of the femoral canal were identified through Principal Component Analysis (PCA), thus generating the mean geometry and the extreme shapes (±2 stdev) of the principal modes of variation.

The shape of the canals obtained from these geometries was reconstructed every 10 mm, best- fitted with an ellipse and the following parameters were evaluated: i) ellipticity, by looking at the difference between axismax and axismin; ii) curvature of the canal, calculating the arc of circumference passing through the shapes’ centroids; iii) conicity, by looking at the maximum/minimum diameter; iv) mean diameter. To understand the association between the main modes and the shape variance, these parameters were compared, for each level of osteotomy, between the two extreme geometries of the main modes of variation.

Results from PCA pointed out that the first three PCs explained more than the 87% of the total variance, for each level of simulated osteotomy. By analysing the extreme geometries for a distal osteotomy (e.g. 80% of the length of the canal), the first PC was associated to a combination of ROC (var%=41%), conicity (var%=28%) and ellipticity (var%=7%). PC2 was still associated with the ROC (var%=16%), while PC3 turned out to be associated with the diameter (var%=38%).

Through the SSM presented in this study, a quantitatively evaluation of the deformation of the intramedullary canal has been made possible. By analysing the extreme geometries obtained from the first three modes of variance, it is clear that the first three PCs accounted for the variations in terms of curvature, conicity, ellipticity and diameter of the femoral canal with a different weight, depending on the level of osteotomy. Through this work, it was also possible to parametrize these variations according to the level of excision. The results given for the segment corresponding to the 80% of the length of the canal showed that, at that specified level, the ROC, conicity and ellipticity were the anatomical parameters with the highest range of variability, followed by the variation in terms of diameter. Therefore, the analysis carried out can provide information about the relevance of these parameters depending on the level of osteotomy suffered by the amputee. In this way, optimal strategies for the design and/or customization of osteo-integrated stems can be offered depending on the patient's residual limb.

Magnetic resonance imaging (MRI) is the gold standard for the diagnosis of the pathologies affecting the glenohumeral joint and the rotator cuff diseases. MRI allows to highlight anatomic discontinuities of both muscles and tendons. However, MRI diagnostic accuracy has not proven to be highly sensitive in distinguishing between a partial-thickness tear and a full-thickness rotator cuff tear. The purpose of this study was to determine if MRI under axial traction can be helpful in increasing MRI sensitivity to identify partial-thickness rotator cuff tears.

The study included 10 patients (4 males and 6 females) who had clinical examination and MRI suggesting a partial-thickness rotator cuff tear. They were candidates for shoulder arthroscopy because of persistent symptoms after at least three months of conservative treatment. The patients underwent a new MRI (under axial traction: MRI-AT) with a 4-kg weight applied to the affected arm. Then the patients underwent arthroscopy to confirm the diagnosis. Patients with a suspected full-thickness rotator cuff tear were excluded from the study.

Patients’ average age was 52.4 years, and the dominant side was affected in 77.7% of the cases. Preoperative Constant-Murley Score was 57. MRI-AT showed that 3 patients were affected by a complete tear of the rotator cuff, 3 patients by a partial-thickness rotator cuff tear and 4 patients had no lesion. The analysis of data showed that: under axial traction the subacromial space increased by 0,2 mm (P value = 0,001075), the superior glenohumeral space decreased by 2.4 mm (P value = 0,07414), the inferior glenohumeral space increased by 0.3 mm (P value = 0,02942), the acromial angle decreased by 1.9° (P value = 0,0002104) and the acromion-glenohumeral angle decreased by 0.3° (P-value = 0,01974). Two experienced evaluators analyzed previous standard MRI and MRI-AT scans in a double-blinded fashion, with inter-rater evaluation of all the images and measures. Intraclass correlation coefficient (ICC) has been utilized to assess the reliability of the measures performed by different operators. ICC always resulted in more than 0.7, showing a high concordance among values in the same group. A comparative evaluation between standard MRI and MRI-AT has been conducted to highlight possible discrepancies and this has been compared to intraoperative findings. Concordance of the values was 89% between standard MRI and MRI-AT and 100% between MRI under axial traction and intraoperative findings.

This study showed a high correlation between the diagnosis achieved with MRI-AT and the intraoperative arthroscopic findings. The use of MRI-AT in clinical practice may improve the diagnostic sensitivity of this method to detect a partial-thickness rotator cuff tear.

Intervertebral disc degeneration (IDD) affects more than 80% of the population all over the world. Current strategies for the treatment of IDD are based on conservative or surgical procedures with the aim of relieving pain. Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy in recent decades, but studies showed that the particularly hostile microenvironment in the intervertebral disc (IVD) can compromise cells survival rate. The use of exosomes, extracellular vesicles released by various cell types, possess considerable economic advantages including low immunogenicity and toxicity. Exosomes allow intercellular communication by conveying functional proteins, RNA, miRNA and lipids between cells. The purpose of this study is to assess the therapeutic effects of exosomes derived from Wharton Jelly mesenchymal stromal cells (WJ-MSC) on human nucleuspulposus cells (hNPC) in an in vitro 3D culture model.

Exosomes (exos) were isolated by tangential flow filtration of WJ-MSC conditioned media and characterized by: quantification with BCA test; morphological observation with TEM, surface marker expression by WB and size evaluation by NTA. Confocal microscopy has been used to identify exosomes marked with PKH26 and monitor fusion and/or incorporation in hNPC. hNPC were isolated from waste surgical material from patients undergoing discectomy (n = 5), expanded, encapsulated in alginate beads and treated with: culture medium (control group); WJ-MSC exos (WJ-exos) at different concentrations (10 μg/ml, 50 μg/ml and 100 μg/ml).

They were then analysed for: cell proliferation (Trypan Blu); viability (Live/Dead Assay); quantification of nitrites (Griess) and glycosaminoglycans, GAG (DMBB). The hNPC in alginate beads treated for 7 days were included in paraffin and histologically analysed to determine the presence of extracellular matrix (ECM) components. Finally, the expression levels of catabolic and anabolic genes were evaluated through real-time polymerase chain reaction (qPCR).

All concentrations of WJ-exos under exam were capable to induce a significant increase in cell proliferation after 10 and 14 days of treatment (p < 0.01 and p < 0.001, respectively). Live/Dead assay showed a decrease in cell death at 50 μg/ml of WJ-exos (p < 0.05). While cellular oxidative stress indicator, nitrite production, was reduced in a dose-dependent way and statistically significant only with 100 μg/ml of WJ-exos (p < 0.05). WJ-exos at 10 and 100 μg/ml induced a significant increase in GAG content (p < 0.05; p < 0.01, respectively) confirmed by Alcian Blu staining. Exos derived from WJ-MSC modulated gene expression levels by increasing expression of ACAN and SOX-9 genes and reducing significantly of IL-6, MMP-1, MMP-13 and ADAMTS-5 levels (p < 0.05; p < 0.01) compared to the control group.

Our results supported the potential use of exosomes from WJ-MSC for the treatment of IDD. Exosomes improved hNPC growth, attenuated ECM degradation and reduced oxidative stress and inflammation. This study offers a new scenario in IVD regeneration, promoting the potential use of extracellular vesicles as an alternative strategy to cell therapy.

Neurological complications in oncological and degenerative spine surgery represent one of the most feared risks of these procedures. Multimodal intraoperative neurophysiological monitoring (IONM) mainly uses methods to detect changes in the patient's neurological status in a timely manner, thus allowing actions that can reverse neurological deficits before they become irreversible. The utopian goal of spinal surgery is the absence of neurological complications while the realistic goal is to optimize the responses to changes in neuromonitoring such that permanent deficits occur less frequently as possible. In 2014, an algorithm was proposed in response to changes in neuromonitoring for deformity corrections in spinal surgery. There are several studies that confirm the positive impact that a checklist has on care. The proposed checklist has been specifically designed for interventions on stable columns which is significantly different from oncological and degenerative surgery. The goal of this project is to provide a checklist for oncological and degenerative spine surgery to improve the quality of care and minimize the risk of neurological deficit through the optimization of clinical decision-making during periods of intraoperative stress or uncertainty.

After a literature review on risk factors and recommendations for responding to IONM changes, 3 surveys were administered to 8 surgeons with experience in oncological and degenerative spine surgery from 5 hospitals in Italy. In addition, anesthesiologists, intraoperative neuro-monitoring teams, operating room nurses participated. The members participated in the optimization and final drafting of the checklist. The authors reassessed and modified the checklist during 3 meetings over 9 months, including a clinical validation period using a modified Delphi process.

A checklist containing 28 items to be considered in responding to the changes of the IONM was created. The checklist was submitted for inclusion in the new recommendations of the Italian Society of Clinical Neurophysiology (SINC) for intraoperative neurophysiological monitoring. The final checklist represents the consensus of a group of experienced spine surgeons. The checklist includes the most important and high-performance items to consider when responding to IONM changes in patients with an unstable spine. The implementation of this checklist has the potential to improve surgical outcomes and patient safety in the field of spinal surgery.

Imaging can provide valuable information about the function of tissues and organs. The capacity for detecting and measuring imaging biomarkers of biological activities, allows for a better understanding of the pathophysiology of any process in the human body, including the musculoskeletal system. This is of particular importance in oncologic, metabolic and rheumatologic diseases, but not limited to these.

In the domain of the musculoskeletal system, functional imaging also means to be able to address biomechanical evaluations.

Weight-bearing imaging and dynamic studies have a prominent role. All imaging techniques (X-rays, CT, MR, ultrasound) are in demand, and offer different applications, specific equipment and novel methods for addressing this.

Functional imaging is also essential to drive minimally invasive treatments – i.e. interventional radiology, and new treatment approaches move together with the advances on imaging guidance methods.

On both the diagnostic and the interventional side, the increasing availability of dedicated equipment and the development of specific imaging methods and protocols greatly helps the transition from research to clinical practice.

Menisci are crucial structures for knee homeostasis: they provide increase of congruence between the articular surfaces of the distal femur and tibial plateau, bear loading, shock absorption, lubrication, and proprioception. After a meniscal lesion, the golden rule, now, is to save as much meniscus as possible: only the meniscus tissue which is identified as unrepairable should be excised and meniscal sutures find more and more indications. Several different methods have been proposed to improve meniscal healing. They include very basic techniques, such as needling, abrasion, trephination and gluing, or more complex methods, such as synovial flaps, meniscal wrapping, or the application of fibrin clots. Basic research of meniscal substitutes has also become very active in the last decades. The features needed for a meniscal scaffold are: promotion of cell migration, it should be biomimetic and biocompatible, it should resist forces applied and transmitted by the knee, it should slowly biodegrade and should be easy to handle and implant. Several materials have been tested, that can be divided into synthetic and biological. The first have the advantage to be manufactured with the desired shapes and sizes and with precise porosity dimension and biomechanical characteristics. To date, the most common polymers are polylactic acid (PGA); poly-(L)-lactic acid (PLLA); poly- (lactic-co-glycolic acid) (PLGA); polyurethane (PU); polyester carbon and polycaprolactone (PCL). The possible complications, more common in synthetic than natural polymers are poor cell adhesion and the possibility of developing a foreign body reaction or aseptic inflammation, leading to alter the joint architecture and consequently to worsen the functional outcomes. The biological materials that have been used over time are the periosteal tissue, the perichondrium, the small intestine submucosa (SIS), acellular porcine meniscal tissue, bacterial cellulose. Although these have a very high biocompatibility, some components are not suitable for tissue engineering as their conformation and mechanical properties cannot be modified. Collagen or proteoglycans are excellent candidates for meniscal engineering, as they maintain a high biocompatibility, they allow for the modification of the porosity texture and size and the adaptation to the patient meniscus shape. On the other hand, they have poor biomechanical characteristics and a more rapid degradation rate, compared to others, which could interfere with the complete replacement by the host tissue. An interesting alternative is represented by hydrogel scaffolds. Their semi-liquid nature allows for the generation of scaffolds with very precise geometries obtained from diagnostic images (i.e. MRI).

Promising results have been reported with alginate and polyvinyl alcohol (PVA). Furthermore, hydrogel scaffolds can be enriched with growth factors, platelet-rich plasma (PRP) and Bone Marrow Aspirate Concentrate (BMAC). In recent years, several researchers have developed meniscal scaffolds combining different biomaterials, to optimize the mechanical and biological characteristics of each polymer. For example, biological polymers such as chitosan, collagen and gelatin allow for excellent cellular interactions, on the contrary synthetic polymers guarantee better biomechanical properties and greater reliability in the degradation time. Three-dimensional (3D) printing is a very interesting method for meniscus repair because it allows for a patient-specific customization of the scaffolds. The optimal scaffold should be characterized by many biophysical and biochemical properties as well as bioactivity to ensure an ECM-like microenvironment for cell survival and differentiation and restoration of the anatomical and mechanical properties of the native meniscus. The new technological advances in recent years, such as 3D bioprinting and mesenchymal stem cells management will probably lead to an acceleration in the design, development, and validation of new and effective meniscal substitutes.

Mechanical failure of spine posterior fixation in the lumbar region Is suspected to occur more frequently when the sagittal balance is not properly restored. While failures at the proximal extremity have been studied in the literature, the lumbar distal junctional pathology has received less attention. The aim of this work was to investigate if the spinopelvic parameters, which characterize the sagittal balance, could predict the mechanical failure of the posterior fixation in the distal lumbar region.

All the spine surgeries performed in 2017-2019 at Rizzoli Institute were retrospectively analysed to extract all cases of lumbar distal junctional pathology. All the revision surgeries performed due to the pedicle screws pull-out, or the breakage of rods or screws, or the vertebral fracture, or the degenerative disc disease, in the distal extremity, were included in the junctional (JUNCT) group. A total of 83 cases were identified as JUNCT group. All the 241 fixation surgeries which to date have not failed were included in the control (CONTROL) group. Clinical data were extracted from both groups, and the main spinopelvic parameters were assessed from sagittal standing preoperative (pre-op) and postoperative (post-op) radiographs with the software Surgimap (Nemaris). In particular, pelvic incidence (PI), sagittal vertical axis (SVA), pelvic tilt (PT), T1 pelvic angle (TPA), sacral slope (SS) and lumbar lordosis (LL) have been measured.

In JUNCT, the main failure cause was the screws pull-out (45%). Spine fixation with 7 or more levels were the most common in JUNCT (52%) in contrast to CONTROL (14%). In CONTROL, PT, TPA, SS and PI-LL were inside the recommended ranges of good sagittal balance. For these parameters, statistically significant differences were observed between pre-op and post-op (p<0.0001, p=0.01, p<0.0001, p=0.004, respectively, Wilcoxon test). In JUNCT, the spinopelvic parameters were out of the ranges of the good sagittal balance and the worsening of the balance was confirmed by the increase in PT, TPA, SVA, PI-LL and by the decrease of LL (p=0.002, p=0.003, p<0.0001, p=0.001, p=0.001, respectively, paired t-test) before the revision surgery. TPA (p=0.003, Kolmogorov-Smirnov test) and SS (p=0.03, unpaired t-test) differed significantly in pre-op between JUNCT and CONTROL. In post-op, PI-LL was significantly different between JUNCT and CONTROL (p=0.04, unpaired t-test). The regression model of PT vs PI was significantly different between JUNCT and CONTROL in pre-op (p=0.01, Z-test).

These results showed that failure is most common in long fused segments, likely due to long lever arms leading to implant failure. If the sagittal balance is not properly restored, after the surgery the balance is expected to worsen, eventually leading to failure: this effect was confirmed by the worsening of all the spinopelvic parameters before the revision surgery in JUNCT. Conversely, a good sagittal balance seems to avoid a revision surgery, as it is visible is CONTROL. The mismatch PI-LL after the fixation seems to confirm a good sagittal balance and predict a good correction. The linear regression of PT vs PI suggests that the spine deformity and pelvic conformation could be a predictor for the failure after a fixation.

Summary:

Hamstring tendons (HT) represent a widely used autograft for ACL reconstruction. Harvesting, processing and pretensioning procedures together with the time out of the joint could theoretically hamper tendon cells (TCs) viability. The authors hypothesize that HT cells are not impaired at the end of the surgical procedures and their tenogenic phenotype may be strongly improved by exposure to PEMF.

Biomedical imaging is essential in the diagnosis of musculoskeletal pathologies and postoperative evaluations. In this context, Cone-Beam technology-based Computed Tomography (CBCT) can make important contributions in orthopaedics. CBCT relies on divergent cone X-rays on the whole field of view and a rotating source-detector element to generate three-dimensional (3D) volumes. For the lower limb, they can allow acquisitions under real loading conditions, taking the name Weight-Bearing CBCT (WB-CBCT). Assessments at the foot, ankle, knee, and at the upper limb, can benefit from it in situations where loading is critical to understanding the interactions between anatomical structures. The present study reports 4 recent applications using WB-CBCT in an orthopaedic centre.

Patient scans by WB-CBCT were collected for examinations of the lower limb in monopodal standing position. An initial volumetric reconstruction is obtained, and the DICOM file is segmented to obtain 3D bone models. A reference frame is then established on each bone model by virtual landmark palpation or principal component analysis. Based on the variance of the model point cloud, this analysis automatically calculates longitudinal, vertical and mid-lateral axes. Using the defined references, absolute or relative orientations of the bones can be calculated in 3D.

In 19 diabetic patients, 3D reconstructed bone models of the foot under load were combined with plantar pressure measurement. Significant correlations were found between bone orientations, heights above the ground, and pressure values, revealing anatomic areas potentially prone to ulceration. In 4 patients enrolled for total ankle arthroplasty, preoperative 3D reconstructions were used for prosthetic design customization, allowing prosthesis-bone mismatch to be minimized. 20 knees with femoral ligament reconstruction were acquired with WB-CBCT and standard CT (in unloading). Bone reconstructions were used to assess congruency angle and patellar tilt and TT-TG. The values obtained show differences between loading and unloading, questioning what has been observed so far. Twenty flat feet were scanned before and after Grice surgery. WB-CBCT allowed characterization of the deformity and bone realignment after surgery, demonstrating the complexity and multi-planarity of the pathology.

These applications show how a more complete and realistic 3D geometric characterization of the of lower limb bones is now possible in loading using WB-CBCT. This allows for more accurate diagnoses, surgical planning, and postoperative evaluations, even by automatisms. Other applications are in progress.

Introduction:

Most of the published papers on AI based diagnosis have focused on the algorithm's diagnostic performance in a ‘binary’ setting (i.e. disease vs no disease). However, no study evaluated the actual value for the clinicians of an AI based approach in diagnostic. Detection of Traumatic thoracolumbar (TL) fractures is challenging on planar radiographs, resulting in significant rates of missed diagnoses (30-60%), thus constituting a field in which a performance improvement is needed. Aim of this study is therefore to evaluate the value provided by AI generated saliency maps (SM), i.e. the maps that highlight the AI identified region of interests.

Scoliosis correction surgery is one of the longest and most complex procedures of all orthopedic surgery. The complication rate is therefore not negligible and is particularly high when the surgery is performed in patients with neuromuscular or connective tissue disease or complex genetic syndromes. In fact, these patients have various comorbidities and organ deficits (respiratory capacity, swallowing / nutrition, heart function, etc.), which can compromise the outcome of the surgery. In these cases, an accurate assessment and preparation for surgery is essential, also making use of external consultants. To make this phase simpler, more effective and homogeneous, a multidisciplinary path of peri-operative optimization is being developed in our Institute, which also includes the possibility of post-operative hospitalization for rehabilitation and recovery. The goal is to improve the basic functional status as much as possible, in order to ensure faster functional recovery and minimize the incidence of peri-operative complications, to be assessed by clinical audit. The path model and the preliminary results on the first patients managed according to the new modality are presented here.

The multidisciplinary path involves the execution of the following assessments / interventions: • Pediatric visit with particular attention to the state of the upper airways and the evaluation of chronic or frequent inflammatory states • Cardiological Consultation with Echocardiogram. • Respiratory Function Tests, Blood Gas Analysis and Pneumological Consultation to evaluate indications for preoperative respiratory physiotherapy cycles, Non-Invasive Ventilation (NIV) cycles, Cough Machine. Possible Polysomnography. • Nutrition consultancy to assess the need for nutritional preparation in order to improve muscle trophism. • Consultation of the speech therapist in cases of dysphagia for liquids and / or solids. • Electroencephalogram and Neurological Consultation in epileptic patients. • Physiological consultation in patients already being treated with a cough machine and / or NIV. • Availability of postoperative hospitalization in the rehabilitation center (with skills in respiratory and neurological rehabilitation) for the most complex cases. When all the appropriate assessments have been completed, the anesthetist in charge at our Institute examines the clinical documentation and establishes whether the path can be considered complete and whether the patient is ready for surgery. At the end of the surgery, the patient is admitted to the Post-operative Intensive Care Unit of the Institute. If necessary, a new program of postoperative rehabilitation (respiratory, neuromotor, etc.) is programmed in a specialist reference center.

To date, two patients have been referred to the preoperative optimization path: one with Ullrich Congenital Muscular Dystrophy, and one with 6q25 Microdeletion Syndrome. In the first case, the surgery was performed successfully, and the patient was discharged at home. In the second case, after completing the optimization process, the surgery was postponed due to the finding of urethral malformation with the impossibility of bladder catheterization, which made it necessary to proceed with urological surgery first.

The preliminary case series presented here is still very limited and does not allow evaluations on the impact of the program on the clinical practice and the complication rate. However, these first experiences made it possible to demonstrate the feasibility of this complex multidisciplinary path in which a network of specialists takes part.

Low back pain (LBP) is the leading cause of disability worldwide. Recently, treatment of the intervertebral disc (IVD) with stem cells has been used for the treatment of degenerate discs (IDD) which cause at least the 40% of LBP cases. Despite pain reduction, follow-up in clinical studies have not shown an improvement in the structural integrity of IVD. A valid alternative could be the use of progenitor disc cells (notocordal cells, NC) or of their precursors. Mesendoderm progenitor cells (MEPC) have the ability to replicate and differentiate toward NC. In this preliminary study we evaluated in a preclinical large animal IDD model the viability and NC differentiation of MEPC derived from induced pluripotent stem cells (iPSC).

MEPC, derived from iPSC and developed during the iPSpine project (# 825925), were thawed and plated on laminin for 24h and labeled with PKH26.

Two adult sheep were subjected to nucleotomy of five lumbar discs for the induction of IDD. After 5 weeks, 3 of the 5 degenerate discs were treated with MEPC at 3 different doses (low, medium and high). One sheep was sacrificed after 7 days and the other after 30 days from the treatment injection procedure. Clinical parameters were collected to evaluate the safety of treatment. Discs were paraffin embedded and analysed using histological techniques. Survival (PKH26), proliferation (PCNA), notocordal cell differentiation (Brachyury, Cytokeratin 8/18/19, Sox9, Foxa2) and endodermal differentiation (Sox17) were evaluated.

After the injection of the cells, both sheep lost about 20% of body weight. The analysis showed that only in discs treated with the highest dose the PKH26 stained cells resulted alive after 30 days from the procedure. These cells turn out to be:

This preliminary study shows that MEPC, derived from iPSC and injected into ovine discs degenerated by nucleotomy, are able to survive 30 days from treatment and differentiate within the disc predominantly towards the notocordal phenotype.

Spinal surgery deals with the treatment of different pathological conditions of the spine such as tumors, deformities, degenerative disease, infections and traumas. Research in the field of vertebral surgery can be divided into two main areas: 1) research lines transversal to the different branches; 2) specific research lines for the different branches.

The transversal lines of research are represented by strategies for the reduction of complications, by the development of minimally invasive surgical techniques, by the development of surgical navigation systems and by the development of increasingly reliable systems for the control of intra-operative monitoring.

Instead, specific lines of research are developed within the different branches. In the field of oncological pathology, the current research concerns the development of in vitro models for the study of metastases and research for the study of targeted treatment methods such as electrochemotherapy and mesenchymal stem cells for the treatment of aneurysmal bone cysts. Research in the field of spinal deformities is focused on the development of increasingly minimally invasive methods and systems which, combined with appropriate pharmacological treatments, help reduce trauma, stress and post-operative pain. Scaffolds based on blood clots are also being developed to promote vertebral fusion, a fundamental requirement for improving the outcome of vertebral arthrodesis performed for the treatment of degenerative disc disease. To improve the management and the medical and surgical treatment of vertebral infections, research has focused on the definition of multidisciplinary strategies aimed at identifying the best possible treatment path. Thus, flow-charts have been created which allow to manage the patient suffering from vertebral infection. In addition, dedicated silver-coated surgical instrumentation and bone substitutes have been developed that simultaneously guarantee mechanical stability and reduce the risk of further local infection. In the field of vertebral traumatology, the most recent research studies have focused on the development of methods for the biostimulation of the bone growth in order to obtain, when possible, healing without surgery. Methods have also been developed that allow the minimally invasive percutaneous treatment of fractures by means of vertebral augmentation with PMMA, or more recently with the use of silicone which from a biomechanical point of view has an elastic modulus more similar to that of bone. It is clear that scientific research has changed clinical practice both in terms of medical and surgical management of patients with spinal pathologies. The results obtained stimulate the basic research to achieve even more. For this reason, new lines of research have been undertaken which, in the oncology field, aim at developing increasingly specific therapies against target receptors. Research efforts are also being multiplied to achieve regeneration of the degenerated intervertebral disc and to develop implants with characteristics increasingly similar to those of bone in order to improve mechanical stability and durability over time. Photodynamic therapies are being developed for the treatment of infections in order to reduce the use of antibiotic therapies. Finally, innovative lines of research are being launched to treat and regenerate damaged nerve structures with the goal, still far from today, of making patients with spinal cord injuries to walk.

Among the advanced technology developed and tested for orthopaedic surgery, the Rizzoli (IOR) has a long experience on custom-made design and implant of devices for joint and bone replacements. This follows the recent advancements in additive manufacturing, which now allows to obtain products also in metal alloy by deposition of material layer-by-layer according to a digital model. The process starts from medical image, goes through anatomical modelling, prosthesis design, prototyping, and final production in 3D printers and in case post-production. These devices have demonstrated already to be accurate enough to address properly the specific needs and conditions of the patient and of his/her physician. These guarantee also minimum removal of the tissues, partial replacements, no size related issues, minimal invasiveness, limited instrumentation. The thorough preparation of the treatment results also in a considerable shortening of the surgical and of recovery time. The necessary additional efforts and costs of custom-made implants seem to be well balanced by these advantages and savings, which shall include the lower failures and revision surgery rates. This also allows thoughtful optimization of the component-to-bone interfaces, by advanced lattice structures, with topologies mimicking the trabecular bone, possibly to promote osteointegration and to prevent infection. IOR's experience comprises all sub-disciplines and anatomical areas, here mentioned in historical order. Originally, several systems of Patient-Specific instrumentation have been exploited in total knee and total ankle replacements. A few massive osteoarticular reconstructions in the shank and foot for severe bone fractures were performed, starting from mirroring the contralateral area. Something very similar was performed also for pelvic surgery in the Oncology department, where massive skeletal reconstructions for bone tumours are necessary. To this aim, in addition to the standard anatomical modelling, prosthesis design, technical/technological refinements, and manufacturing, surgical guides for the correct execution of the osteotomies are also designed and 3D printed. Another original experience is about en-block replacement of vertebral bodies for severe bone loss, in particular for tumours. In this project, technological and biological aspects have also been addressed, to enhance osteointegration and to diminish the risk of infection. In our series there is also a case of successful custom reconstruction of the anterior chest wall. Initial experiences are in progress also for shoulder and elbow surgery, in particular for pre-op planning and surgical guide design in complex re-alignment osteotomies for severe bone deformities. Also in complex flat-foot deformities, in preparation of surgical corrections, 3D digital reconstruction and 3D printing in cheap ABS filaments have been valuable, for indication, planning of surgery and patient communication; with special materials mimicking bone strength, these 3D physical models are precious also for training and preparation of the surgery. In Paediatric surgery severe multi planar & multifocal deformities in children are addressed with personalized pre-op planning and custom cutting-guides for the necessary osteotomies, most of which require custom allografts. A number of complex hip revision surgeries have been performed, where 3D reconstruction for possible final solutions with exact implants on the remaining bone were developed. Elective surgery has been addressed as well, in particular the customization of an original total ankle replacement designed at IOR. Also a novel system with a high-tibial-osteotomy, including a custom cutting jig and the fixation plate was tested. An initial experience for the design and test of custom ankle & foot orthotics is also in progress, starting with 3D surface scanning of the shank and foot including the plantar aspect. Clearly, for achieving these results, multi-disciplinary teams have been formed, including physicians, radiologists, bioengineers and technologists, working together for the same goal.

Chronic Achilles tendinopathy is characterised by sub-acute inflammation with pro-inflammatory type 1 macrophages (M1), tissue degeneration and consequent partial or total tendon injury. Control of the inflammatory response and M1-to-M2 macrophage polarisation can favour tendon healing both directly and indirectly, by allowing for the regenerative process driven by local mesenchymal stem cells.

Ten patients (3 females and 7 males aged between 32 and 71 years old) with partial Achilles tendon injury were treated with injections of autologous peripheral blood mononuclear cells (PB-MNCs). The cell concentrate was obtained from 100-120 cc of each patient's blood with a selective point-of-care filtration system. PB-MNCs remained trapped in the filter and were injected immediately after sampling. Around 60% of the PB-MNC concentrate was injected directly into the injured area, while the remaining 40% was injected in smaller amounts into the surrounding parts of the Achilles tendon affected by tendinosis.

All patients were evaluated both clinically with the help of the American Orthopaedic Foot & Ankle Society (AOFAS) scale, and radiologically (MRI examination) at baseline and 2 months after the PB-MNC injection. A clinical reassessment with the AOFAS scale was also performed 6 months after the intervention. The rehabilitation protocol implied full weight-bearing walking immediately after the procedure, light physical activity 3-4 days after the injection, and physiotherapist-assisted stretching exercises and eccentric training.

In all patients, functional and radiological signs of tendon healing processes were detected as early as 2 months after a single treatment and the AOFAS scale rose from the initial mean value of 37.5 (baseline) to 85.4 (6 months).

Our preliminary results indicate that regenerative therapies with PB-MNCs can prove useful for partial Achilles tendon injuries as a valid alternative to surgical options, especially when other conservative approaches have failed. Advantages of this therapy include rapid execution, no need for an operating theatre, easy reproducibility, quick recovery and good tolerability regardless of the patient's age (the procedure is not to be performed in subjects who are below 18 years old). Further studies on the topic are recommended to confirm these observations.

Hip Osteoarthritis (HOA) is the most common joint disorder and a major cause of disability in the adult population, leading to total hip replacement (THR). Recently, evidence has mounted for a prominent etiologic role of femoroacetabular impingement (FAI) in the development of early OA in the non-dysplastic hip. FAI is a pathological mechanical process, caused by abnormalities of the acetabulum and/or femur leading to damage the soft tissue structures. FAI can determine chondro-labral damage and groin pain in young adults and can accelerate HOA progression in middle-aged adults.

The aim of the study was to determine if the presence of calcium crystal in synovial fluid (SF) at the time of FAI surgery affects the clinical outcomes to be used as diagnostic and predictive biomarker.

49 patients with FAI undergoing arthroscopy were enrolled after providing informed consent; 37 SFs were collected by arthrocentesis at the time of surgery and 35 analyzed (66% males), median age 35 years with standard deviation (SD) 9.7 and body mass index (BMI) 23.4 kg/m²; e SD 3.

At the time of surgery, chondral pathology using the Outerbridge score, labral pathology and macroscopic synovial pathology based on direct arthroscopic visualization were evaluated. Physical examination and clinical assessment using the Hip disability & Osteoarthritis Outcome Score (HOOS) were performed at the time of surgery and at 6 months of follow up. As positive controls of OA signs, SF samples were also collected from cohort of 15 patients with HOA undergoing THR and 12 were analysed.

45% FAI patients showed CAM deformity; 88% presented labral lesion or instability and 68% radiographic labral calcification. 4 patients out of 35 showed moderate radiographic signs of OA (Kellegren-Lawrence score = 3). Pre-operative HOOS median value was 61.3% (68.10-40.03) with interquartile range (IQR) of 75-25% and post-operative HOOS median value 90% with IQR 93.8-80.60. In both FAI and OA patients the calcium crystal level in SFs negatively correlated with glycosaminoglycan (component of the extracellular matrix) released, which is a marker of cartilage damage (Spearman rho=-0.601, p<0.001).

In FAI patients a worst articular function after surgery, measured with the HOOS questionnaire, was associated with both acetabular and femoral chondropathy and degenerative labral lesion. Moreover, radiographic labral calcification was also significantly associated with pain, worst articular function and labral lesion. Calcium crystal level in SFs was associated with labral lesions and OA signs.

We concluded that the levels of calcium crystals in FAI patients are correlated with joint damage, OA signs and worst post-operative outcome. The presence of calcium crystals in SF of FAI patients might be a potential new biomarker that might help clinicians to make an early diagnosis, evaluate disease progression and monitor treatment response.

Fracture nonunion is a severe clinical problem for the patient, as well as for the clinician. About 5-20% of fractures does not heal properly after more than six months, with a 19% nonunion rate for tibia, 12% for femur and 13% for humerus, leading to patient morbidity, prolonged hospitalization, and high costs.

The standard treatment with iliac crest-derived autologous bone filling the nonunion site may cause pain or hematoma to the patient, as well as major complications such as infection.

The application of mesenchymal autologous cells (MSC) to improve bone formation calls for randomized, open, two-arm clinical studies to verify safety and efficacy.

The ORTHOUNION * project (ORTHOpedic randomized clinical trial with expanded bone marrow MSC and bioceramics versus autograft in long bone nonUNIONs) is a multicentric, open, randomized, comparative phase II clinical trial, approved in the framework of the H2020 funding programme, under the coordination of Enrique Gòmez Barrena of the Hospital La Paz (Madrid, Spain).

Starting from January 2017, patients with nonunion of femur, tibia or humerus have been actively enrolled in Spain, France, Germany, and Italy.

The study protocol encompasses two experimental arms, i.e., autologous bone marrow-derived mesenchymal cells after expansion (‘high dose’ or ‘low dose’ MSC) combined to ceramic granules (MBCP™, Biomatlante), and iliac crest-derived autologous trabecular bone (ICAG) as active comparator arm, with a 2-year follow-up after surgery.

Despite the COVID 19 pandemic with several lockdown periods in the four countries, the trial was continued, leading to 42 patients treated out of 51 included, with 11 receiving the bone graft (G1 arm), 15 the ‘high dose’ MSC (200x10⁶, G2a arm) and 16 the ‘low dose’ MSC (100x10⁶, G2b arm).

The Rizzoli Orthopaedic Institute has functioned as coordinator of the Italian clinical centres (Bologna, Milano, Brescia) and the Biomedical Science and Technologies and Nanobiotechnology Lab of the RIT Dept. has enrolled six patients with the collaboration of the Rizzoli’ 3rd Orthopaedic and Traumatological Clinic prevalently Oncologic.

Moreover, the IOR Lab has collected and analysed the blood samples from all the patients treated to monitor the changes of the bone turnover markers following the surgical treatment with G1, G2a or G2b protocols.

The clinical and biochemical results of the study, still under evaluation, are presented.

* ORTHOUNION Horizon 2020 GA 733288

The inability to replace human muscle in surgical practice is a significant challenge. An artificial muscle controlled by the nervous system is considered a potential solution for this. We defined it as neuromuscular prosthesis. Muscle loss and dysfunction related to musculoskeletal oncological impairments, neuromuscular diseases, trauma or spinal cord injuries can be treated through artificial muscle implantation. At present, the use of dielectric elastomer actuators working as capacitors appears a promising option. Acrylic or silicone elastomers with carbon nanotubes functioning as the electrode achieve mechanical performances similar to human muscle in vitro. However, mechanical, electrical, and biological issues have prevented clinical application to date. In this study, materials and mechatronic solutions are presented which can tackle current clinical problems associated with implanting an artificial muscle controlled by the nervous system. Progress depends on the improvement of the actuation properties of the elastomer, seamless or wireless integration between the nervous system and the artificial muscle, and on reducing the foreign body response. It is believed that by combining the mechanical, electrical, and biological solutions proposed here, an artificial neuromuscular prosthesis may be a reality in surgical practice in the near future.

Glenoid and humeral head bone defects have long been recognized as major determinants in recurrent shoulder instability as well as main predictors of outcomes after surgical stabilization. However, a universally accepted method to quantify them is not available yet. The purpose of the present study is to describe a new CT method to quantify bipolar bone defects volume on a virtually generated 3D model and to evaluate its reproducibility.

A cross-sectional observational study has been conducted. Forty CT scans of both shoulders were randomly selected from a series of exams previously acquired on patients affected by anterior shoulder instability. Inclusion criterion was unilateral anterior shoulder instability with at least one episode of dislocation. Exclusion criteria were: bilateral shoulder instability; posterior or multidirectional instability, previous fractures and/or surgery to both shoulders; congenital or acquired inflammatory, neurological, or degenerative diseases. For all patients, CT exams of both shoulders were acquired at the same time following a standardized imaging protocol. The CT data sets were analysed on a standard desktop PC using the software 3D Slicer. Computer-based reconstruction of the Hill-Sachs and glenoid bone defect were performed through Boolean subtraction of the affected side from the contralateral one, resulting in a virtually generated bone fragment accurately fitting the defect. The volume of the bone fragments was then calculated. All measurements were conducted by two fellowship-trained orthopaedic shoulder surgeons. Each measurement was performed twice by one observer to assess intra-observer reliability. Inter and intra-observer reliability were calculated. Intraclass Correlation Coefficients (ICC) were calculated using a two-way random effect model and evaluation of absolute agreement. Confidence intervals (CI) were calculated at 95% confidence level for reliability coefficients. Reliability values range from 0 (no agreement) to 1 (maximum agreement).

The study included 34 males and 6 females. Mean age (+ SD) of patients was 36.7 + 10.10 years (range: 25 – 73 years). A bipolar bone defect was observed in all cases. Reliability of humeral head bone fragment measurements showed excellent intra-observer agreement (ICC: 0.92, CI 95%: 0.85 – 0.96) and very good interobserver agreement (ICC: 0.89, CI 95%: 0.80 – 0.94). Similarly, glenoid bone loss measurement resulted in excellent intra-observer reliability (ICC: 0.92, CI 95%: 0.85 – 0.96) and very good inter-observer agreement (ICC: 0.84, CI 95%:0.72 – 0.91).

In conclusion, matching affected and intact contralateral humeral head and glenoid by reconstruction on a computer-based virtual model allows identification of bipolar bone defects and enables quantitative determination of bone loss.

The risk of falls in patients undergoing orthopedic procedures is particularly significant in terms of health and socioeconomic effects. The literature analyzed closely this risk following procedures performed on the lower limb, but the implications following procedures on the upper limb remain to be investigated. Interestingly, it is not clear whether the increased risk of falling in patients undergoing shoulder surgery is due to preexisting risk factors at surgery or postoperative risk factors, such as anesthesiologic effects, opioid medications used for pain control, or brace use. Only one prospective study examined gait and fall risk in patients using a shoulder abduction brace (SAB) after shoulder surgery, revealing that the brace adversely affected gait kinematics with an increase in the risk of falls. The main purpose of the study was to investigate the influence of SAB on gait parameters in patients undergoing shoulder surgery.

Patients undergoing elective shoulder surgery (arthroscopic rotator cuff repair, reverse total shoulder arthroplasty, and Latarjet procedure), who used a 15° SAB in the postoperative period, were included. Conversely, patients age > 65 years old, with impaired lower extremity function (e.g., fracture sequelae, dysmorphism, severe osteo-articular pathology), central and peripheral nervous system pathologies, and cardiac/respiratory/vascular insufficiency were excluded. Participants underwent kinematic analysis at four different assessment times: preoperative (T0), 24 hours after surgery (T1), 1 week after surgery (T2), and 1 week after SAB removal (T3). The tests used for kinematic assessment were the Timed Up and Go (TUG) and the 10-meter test (10MWT), both of which examine functional mobility. Agility and balance were assessed by a TUG test (transitions from sitting to standing and vice versa, walking phase, turn-around), while gait (test time, cadence, speed, and pelvic symmetry) was evaluated by the 10MWT. Gait and functional mobility parameters during 10MWT and TUG tests were assessed using the BTS G-Walk sensor (G-Sensor 2). One-way ANOVA for repeated measures was conducted to detect the effects of SAB on gait parameters and functional mobility over time. Statistical analysis was performed with IBM®SPSS statistics software version 23.0 (SPSS Inc., Chicago, IL, USA), with the significant level set at p<0.05.

83% of the participants had surgery on the right upper limb. A main effect of time for the time of execution (duration) (p=0.01, η2=0.148), speed (p<0.01, η2=0.136), cadence (p<0.01, η2=0.129) and propulsion-right (R) (p<0.05, η2=0.105) and left (L) (p<0.01, η2=0.155) in the 10MWT was found. In the 10MWT, the running time at T1 (9.6±1.6s) was found to be significantly longer than at T2 (9.1±1.3s, p<0.05) and at T3 (9.0±1.3s, p=0.02). Cadence at T1 (109.7±10.9steps/min) was significantly lower than at T2 (114.3 ±9.3steps/min, p<0.01) and T3 (114.3±9.3steps/min, p=0.02). Velocity at T1 (1.1±0.31m/s) was significantly lower than at T2 (1.2± 0.21m/s, p<0.05). No difference was found in the pelvis symmetry index. No significant differences were found during the TUG test except for the final rotation phase with T2 value significantly greater than T3 (1.6±0.4s vs 1.4±0.3s, p<0.05). No statistically significant differences were found between T0 and T2 and between T0 and T3 in any of the parameters analyzed. Propulsion-R was significantly higher at T3 than T1 (p<0.01), whereas propulsion-L was significantly lower at T1 than T0 (p<0.05) and significantly higher at T2 and T3 than T1 (p<0.01). Specifically, the final turning phase was significantly higher at T2 than T3 (p<0.01); no significant differences were found for the duration, sit to stand, mid-turning and stand to sit phases.

The results demonstrated that the use of the abduction brace affects functional mobility 24 hours after shoulder surgery but no effects were reported at longer term observations.

In the last years, 3d printing has progressively grown and it has reached a solid role in clinical practice. The main applications brought by 3d printing in orthopedic surgery are: preoperative planning, custom-made surgical guides, custom-made im- plants, surgical simulation, and bioprinting. The replica of the patient's anatomy, starting from the elaboration of medical volumetric images (CT, MRI, etc.), allows a progressive extremization of treatment personalization that could be tailored for every single patient. In complex cases, the generation of a 3d model of the patient's anatomy allows the surgeons to better understand the case — they can almost “touch the anatomy” —, to perform a more ac- curate preoperative planning and, in some cases, to perform device positioning before going to the surgical room (i.e. joint arthroplasty). 3d printing is also commonly used to produce surgical cutting guides, these guides are positioned intraoperatively on given landmarks to guide the surgeon to perform a specific surgical act (bone osteotomy, bone resection, implant position, etc.). In total knee arthroplasty, custom-made cutting guides have been developed to help the surgeon align the femoral and tibial components to the pre-arthritic condition with- out the use of the intramedullary femoral guide. 3d printed custom-made implants represent an emerging alternative to biological reconstructions especially after oncologic resection surgery or in case of complex arthroplasty revision surgery. Custom-made implants are designed to re- place the original shape and size of the patient's bone and they allow an extreme personalization of the treatment for every single patient. Patient-specific surgical simulation is a new frontier that promises great benefits for surgical training. a solid 3d model of the patient's anatomy can faithfully reproduce the surgical complexity of the patient and it allows to generate surgical simulators with increasing difficulty to adapt the difficulties of the course with the level of the trainees performing structured training paths: from the “simple” case to the “complex” case.

Chordoma of the cervical spine is a rare but life-threatening disease with a relentless tendency towards local recurrence. Wide en bloc resection is recommended, but it is frequently not feasible in the cervical spine. Radiation therapy including high-energy particle therapy is commonly used as adjuvant therapy. The goal of this study was to examine treatment and outcome of patients with chordoma of the cervical spine.

Patients affected by cervical spine chordoma who underwent surgery at the Rizzoli Institute and University Hospital of Modena, between 2007 and 2021 were identified. The clinical, pathologic, and radiographic data were reviewed in all cases. Patient outcomes including local recurrence and disease-specific survival (DSS) were analyzed using chi-square test and Kaplan-Meier survival analysis.

Characteristics of the 29 patients (10 females; 19 males) included: median age at surgery 52.0 years (IQR 35.5 - 62.5 years), 10 (35%) involved upper cervical spine, 16 (55%) with tumors in the mid cervical spine, and 4 in the lower cervical spine (10%). Median tumor volume was 16 cm³ (IQR 8.7 - 20.8). Thirteen patients (45%) were previously treated surgically while 9 patients (31%) had previous radiation therapy. All patients underwent surgery: en bloc resection was passible in 4 patients (14 %), seventeen patients (59%) were treated with gross total resection while 8 patients (27%) underwent subtotal resection. Tumor volume was associated with a significantly higher risk of intraoperative complications (p < 0.01). Nineteen patients (65%) received adjuvant high-energy particle therapy. The median follow-up was 26 months (IQR 11 - 44). Twelve patients (41%) had local recurrence of disease. Patients treated with adjuvant high-energy particle therapy had a significant higher local control than patients who received photons or no adjuvant treatment (p = 0.01). Recurrence was the only factor significantly associated with worse DSS (p = 0.03 – OR 1.7), being the survival of the group of patients with recurrent disease 58.3% while the survival of the group of patients with no recurrent disease was 100%.

Post-operative high-energy particle therapy improved local control in patients with cervical chordoma after surgical resection. Increased tumor volume was associated with increased risk of intraoperative complications. Recurrence of the disease was the only factor significantly associated with disease mortality.

Introduction:

Exercise has showed to reduce pain and improve function in patients with discogenic low back pain (LBP). Although there is currently no biologic evidence that the intervertebral disc (IVD) can respond to physical exercise in humans, a recent study has shown that chronic running exercise is associated with increased IVD hydration and hypertrophy1. Irisin, a myokine released upon muscle contraction, has demonstrated to yield anabolic effects on different cell types, including chondrocytes2. This study aimed to investigate the effect of irisin on human nucleus pulposus cells (hNPCs). Our hypothesis is that irisin may improve hNPCs metabolism and proliferation.

Recently, there is ongoing evidence regarding rapid recovery after orthopaedic surgery, with advantages for the patient relative to post operative pain, complications and functional recovery. The aim of this study is to present our experience in rapid recovery for adolescent idiopathic scoliosis in the last 2 years.

Retrospective study of 36 patients with adolescent idiopathic scoliosis, (age range 11 to 18 years) treated with spinal thoraco-lumbar posterior fusion with rapid post-operative recovery, compared with a similar group, treated with traditional protocol.

We found a statistically significant difference in terms of length-of-stay, patient-controlled-analgesia and use of oppioid and post operative blood transfusions. There was no difference in post operative infection rate.

Our experience shows better functional recovery, satisfactory controlled analgesia and reduction in costs of hospitalization with the use of ERAS protocols.

Osteoporosis is a worldwide disease resulting in the increase of bone fragility and enhanced fracture risk in adults. In the context of osteoporotic fractures, bone tissue engineering (BTE), i.e., the use of bone substitutes combining biomaterials, cells, and bone inducers, is a potential alternative to conventional treatments. Pre-clinical testing of innovative scaffolds relies on in vitro systems where the simultaneous presence of osteoblasts (OBs) and osteoclasts (OCs) is required to mimic their crosstalk and molecular cooperation for bone remodelling. To this aim, two composite materials based on type I collagen were developed, containing either strontium-enriched mesoporous bioactive glasses or rod-like hydroxyapatite nanoparticles. Following chemical crosslinking with genipin, the nanostructured materials were tested for 2–3 weeks with an indirect co-culture of human trabecular bone-derived OBs and buffy coat-derived OC precursors. The favourable structural and biological properties of the materials proved to successfully support the viability, adhesion, and differentiation of bone cells, encouraging a further investigation of the two bioactive systems as biomaterial inks for the 3D printing of more complex scaffolds for BTE.

The Spine Surgery Unit of IRCCS Istituto Ortopedico Rizzoli is dedicated to the diagnosis and the treatment of vertebral pathologies of oncologic, degenerative, and post-traumatic origin. To achieve increasingly challenging goals, research has represented a further strength for Spinal Surgery Unit for several years. Thanks to the close synergy with the Complex Structure Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, extensive research was carried out. The addition of the research activities intensifies a complementary focus and provides a unique opportunity of innovation. The overall goal of spine research for the Spine Surgery Unit and for the Complex Structure Surgical Sciences and Technologies is and has been to:

- investigate the factors that influence normal spine function;

- engineer and validate new and advanced strategies for improving segmental spinal instrumentation, fusion augmentation and grafting;

- develop and characterize advanced and alternative preclinical models of vertebral bone metastasis to test drugs and innovative strategies, taking into account patient individual characteristics and specific tumour subtypes so predicting patient specific responses;

- evaluate the clinical characteristics, treatment modalities, and potential contributing and prognostic factors in patients with vertebral bone metastases;

- realize customized prosthesis to replace vertebral bodies affected by tumours or major traumatic events, specifically engineered to reduce infections, and increase patients’ surgical options.

These efforts have made possible to obtain important results that favour the translation of basic research to application at the patient's bedside, and from here to routine clinical practice (without excluding the opposite pathway, in which the evidence generated by clinical practice helps to guide research). Although translational research can provide patients with valuable therapeutic resources, it is not risk-free. Thus, it is therefore necessary an always close collaboration between researchers and clinicians in order to guarantee the ethicality of translational research, by promoting the good of individuals and minimising the risks.