The effects of dexamethasone (dex), during in vitro human osteogenesis, are contrasting. Indeed, dex downregulates SOX9 during osteogenic differentiation of human bone marrow mesenchymal stromal cells (HBMSCs). However, dex also promotes PPARG expression, resulting in the formation of adipocyte-like cells within the osteogenic monolayers. The regulation of both SOX9 and PPARG seems to be downstream the transactivation activity of the glucocorticoid receptor (GR), thus the effect of dex on SOX9 downregulation is indirect. This study aims at determining whether PPAR-γ regulates SOX9 expression levels, as suggested by several studies.

HBMSCs were isolated from bone marrow of patients with written informed consent. HBMSCs were cultured in different osteogenic induction media containing 10 or 100 nM dex. Undifferentiated cells were used as controls. Cells were treated either with a pharmacological PPAR-γ inhibitor T0070907 (donors n=4) or with a PPARG-targeting siRNA (donors n=2). Differentiation markers or PPAR-γ target genes were analysed by RT-qPCR. Mineral deposition was assessed by ARS staining. Two-way ANOVA followed by a Tukey's multiple comparison test compared the effects of treatments.

At day 7, T0070907 downregulated ADIPOQ and upregulated CXCL8, respectively targets of PPAR-γ-mediated transactivation and transrepression. RUNX2 and SOX9 were also significantly downregulated in absence of dex. PPARG was successfully downregulated by siRNA. ADIPOQ expression was also inhibited, while CXCL8 did not show any significant difference between siRNA treatment groups. RUNX2 was downregulated by the PPARG-siRNA treatment in presence of 100 nM dexamethasone, while SOX9 levels were not affected. ARS showed no change in the mineralization levels when PPARG expression or activity was inhibited.

Understanding how dex regulates HBMSC differentiation is of pivotal importance to refine current in vitro models. These results suggest that PPARG does not mediate SOX9 downregulation. Unexpectedly, RUNX2 expression was also unaltered or even downregulated after PPAR-γ inhibition.

Acknowledgements: AO Foundation, AO Research Institute (CH) and PRIN 2017 MUR (IT) for financial support.

Despite osteoarthritis (OA) representing a large burden for healthcare systems, there remains no effective intervention capable of regenerating the damaged cartilage in OA. Mesenchymal stromal cells (MSCs) are adult-derived, multipotent cells which are a candidate for musculoskeletal cell therapy. However, their precise mechanism of action remains poorly understood.

The effects of an intra-articular injection of human bone-marrow derived MSCs into a knee osteochondral injury model were investigated in C57Bl/6 mice. The cell therapy was retrieved at different time points and single cell RNA sequencing was performed to elucidate the transcriptomic changes relevant to driving tissue repair. Mass cytometry was also used to study changes in the mouse immune cell populations during repair.

Histological assessment reveals that MSC treatment is associated with improved tissue repair in C57Bl/6 mice. Single cell analysis of retrieved human MSCs showed spatial and temporal transcriptional heterogeneity between the repair tissue (in the epiphysis) and synovial tissue. A transcriptomic map has emerged of some of the distinct genes and pathways enriched in human MSCs isolated from different tissues following osteochondral injury. Several MSC subpopulations have been identified, including proliferative and reparative subpopulations at both 7 days and 28 days after injury. Supported by the mass cytometry results, the immunomodulatory role of MSCs was further emphasised, as MSC therapy was associated with the induction of increased numbers of regulatory T cells correlating with enhanced repair in the mouse knee.

The transcriptomes of a retrieved MSC therapy were studied for the first time. An important barrier to the translation of MSC therapies is a lack of understanding of their heterogeneity, and the consequent lack of precision in its use. MSC subpopulations with different functional roles may be implicated in the different phases of tissue repair and this work offers further insights into repair process.

Is Non-Weight-Bearing Necessary? (INWN) is a pragmatic multicentre randomised controlled trial comparing immediate protected weight-bearing (IWB) with non-weight-bearing cast immobilisation (NWB) following ankle fracture fixation (ORIF). This trial compares; functional outcomes, complication rates and performs an economic analysis to estimate cost-utility.

IWB within 24hrs was compared to NWB, following ORIF of all types of unstable ankle fractures. Skeletally immature patients and tibial plafond fractures were excluded. Functional outcomes were assessed by the Olerud-Molander Ankle Score (OMAS) and RAND-36 Item Short Form Survey (SF-36) taken at regular follow-up intervals up to one year. A cost-utility analysis via decision tree modelling was performed to derive an incremental cost effectiveness ratio (ICER). A standard gamble health state valuation model utilising SF-36 scores was used to calculate Quality Adjusted Life Years (QALYs) for each arm.

We recruited 160 patients (80 per arm), aged 15 to 94 years (M = 45.5), 54% female. Complication rates were similar in both groups. IWB demonstrated a consistently higher OMAS score, with significant values at 6 weeks (MD=10.4, p=0.005) and 3 months (MD 12.0, p=0.003). Standard gamble utility values demonstrated consistently higher values (a score of 1 equals perfect health) with IWB, significant at 3 months (Ẋ = 0.75 [IWB] / 0.69 [NWB], p=0.018). Cost-utility analysis demonstrated NWB is €798.02 more expensive and results in 0.04 fewer QALYs over 1 year. This results in an ICER of −€21,682.42/QALY. This negative ICER indicates cost savings of €21,682.42 for every QALY (25 patients = 1 QALY gain) gained implementing an IWB regime.

IWB demonstrates a superior functional outcome, greater cost savings and similar complication rates, compared to NWB following ankle fracture fixation.

We aim to analyze the role of patient-related factors on the yield of progenitor cells in the bone marrow aspiration concentrate (BMAC).

We performed a retrospective analysis of patients who underwent autologous iliac crest-based BMAC therapy between Jan 2021–and June 2021. Patient-related factors such as age, sex, and comorbidities and procedure variables such as aspirate volume were analyzed. The yield of the bone marrow aspiration concentrate was assessed with MNC count and CFU assay from the aspirates.

63 patients with a mean age of 51.33±17.98 years were included in the study. There were 31 males and 32 females in the study population with a mean volume of 67.16±17.312 ml being aspirated from the iliac crest for the preparation of BMAC. The final aspirate had a mean MNC count of 20.16±15.73×10^6 cells which yielded a mean of 11±12 CFUs. We noted significant negative correlation between age and MNC count (r=minus;0.671, p<0.001) and CFUs (r=minus;0.688, p<0.001). We did not find the sex to have any significant role in MNC (p=0.082) count or CFUs formed (p=0.348). The presence of comorbidity significantly reduced the MNC count (p=0.003) and CFUs formed (p=0.005). The aspiration volume significantly negatively correlated with MNC count (r=minus;0.731, p<0.001) and CFUs (r=minus;0.618, p<0.001).

The MNC count and CFUs formed from the BMAC depend on the patient-specific subjective variables such as age, and comorbid conditions present in them. Sex and volume of aspiration do not alter the MNC count or the CFUs formed from BMAC.

Approximately 30% of general practice consultations for musculoskeletal pain are related to tendon disorders, causing substantial personal suffering and enormous related healthcare costs. Treatments are often prone to long rehabilitation times, incomplete functional recovery, and secondary complications following surgical repair. Overall, due to their hypocellular and hypovascular nature, the regenerative capacity of tendons is very poor and intrinsically a disorganized scar tissue with inferior biomechanical properties forms after injury. Therefore, advanced therapeutic modalities need to be developed to enable functional tissue regeneration within a degenerative environment, moving beyond pure mechanical repair and overcoming the natural biological limits of tendon healing.

Our recent studies have focused on developing biologically augmented treatment strategies for tendon injuries, aiming at restoring a physiological microenvironment and boosting endogenous tissue repair. Along these lines, we have demonstrated that the local application of mesenchymal stromal cell-derived small extracellular vesicles (sEVs) has the potential to improve rotator cuff tendon repair by modulating local inflammation and reduce fibrotic scarring. In another approach, we investigated if the local delivery of the tendon ECM protein SPARC, which we previously demonstrated to be essential for tendon maturation and tissue homeostasis, has the potential to enhance tendon healing. Finally, I will present results demonstrating the utility of nanoparticle-delivered, chemically modified mRNAs (cmRNA) to improve tendon repair.

Osteochondral glenoid loss is associated with recurrent shoulder instability. The critical threshold for surgical stabilization is multidimensional and conclusively unknown. The aim of this work was to provide a well- measurable surrogate parameter of an unstable shoulder joint for the frequent anterior-inferior dislocation direction.

The shoulder stability ratio (SSR) of 10 paired human cadaveric glenoids was determined in anterior-inferior dislocation direction. Osteochondral defects were simulated by gradually removing osteochondral structures in 5%-stages up to 20% of the intact diameter. The glenoid morphological parameters glenoid depth, concavity gradient, and defect radius were measured at each stage by means of optical motion tracking. Based on these parameters, the osteochondral stability ratio (OSSR) was calculated. Correlation analyses between SSR and all morphological parameters, as well as OSSR were performed.

The loss of SSR, concavity gradient, depth and OSSR with increasing defect size was significant (all p<0.001). The loss of SSR strongly correlated with the losses of concavity gradient (PCC = 0.918), of depth (PCC = 0.899), and of OSSR (PCC = 0.949). In contrast, the percentage loss based on intact diameter (defect size) correlated weaker with SSR (PCC=0.687). Small osteochondral defects (≤10%) led to significantly higher SSR decrease in small glenoids (diameter <25mm) compared to large (≥ 25mm) ones (p ≤ 0.009).

From a biomechanical perspective, the losses of concavity gradient, glenoid depth and OSSR correlate strong with the loss of SSR. Therefore, especially the loss of glenoidal depth may be considered as a valid and reliable alternative parameter to describe shoulder instability. Furthermore, smaller glenoids are more vulnerable to become unstable in case of small osteochondral loosening. On the other hand, the standardly used percentage defect size based on intact diameter correlates weaker with the magnitude of instability and may therefore not be a valid parameter for judgement of shoulder instability.

Gait analysis is an indispensable tool for scientific assessment and treatment of individuals whose ability to walk is impaired. The high cost of installation and operation are a major limitation for wide-spread use in clinical routine.

Advances in Artificial Intelligence (AI) could significantly reduce the required instrumentation. A mobile phone could be all equipment necessary for 3D gait analysis. MediaPipe Pose provided by Google Research is such a Machine Learning approach for human body tracking from monocular RGB video frames that is detecting 3D-landmarks of the human body.

Aim of this study was to analyze the accuracy of gait phase detection based on the joint landmarks identified by the AI system.

Motion data from 10 healthy volunteers walking on a treadmill with a fixed speed of 4.5km/h (Callis, Sprintex, Germany) was sampled with a mobile phone (iPhone SE 2nd Generation, Apple). The video was processed with Mediapipe Pose (Version 0.9.1.0) using custom python software. Gait phases (Initial Contact - IC and Toe Off - TO) were detected from the angular velocities of the lower legs. For the determination of ground truth, the movement was simultaneously recorded with the AS-200 System (LaiTronic GmbH, Innsbruck, Austria).

The number of detected strides, the error in IC detection and stance phase duration was calculated.

In total, 1692 strides were detected from the reference system during the trials from which the AI-system identified 679 strides. The absolute mean error (AME) in IC detection was 39.3 ± 36.6 ms while the AME for stance duration was 187.6 ± 140 ms.

Landmark detection is a challenging task for the AI-system as can clearly be seen be the rate of only 40% detected strides. As mentioned by Fadillioglu et al., error in TO-detection is higher than in IC-detection.

Dislocation post THA confers a higher risk of re-dislocation (Kotwal et al, 2009). The dual mobility (DM) cup design (1974) was aimed at improving the stability by increasing the femoral head to neck ratio (Cuthbert et al., 2019) combining the ideas of low friction arthroplasty with increased jump distance associated with a big head arthroplasty.

Understand the dislocation rates, rates of aseptic loosening, infection rate and revision rates between the 2 types of constructs to provide current and up-to date evidence.

Medline, pubmed, embase and Cochrane databases were used based on PRISMA guidelines. RevMan software was used for the meta-analysis. Studies (English literature) which used DM construct with atleast 6 months follow-up used as intervention and non DM construct as control were included. 2 independent reviewers conducted the review with a third reviewer in case of difference in opinion regarding eligibility. Primary outcome was dislocation rate and secondary outcome was rate of revision.

564 articles identified out of which 44 articles were screened for full texts and eventually 4 systematic review articles found eligible for the study. Thus, study became a review of systematic reviews. From the 4 systematic reviews, another 35 studies were identified for data extraction and 13 papers were used for meta-analysis. Systematic reviews evaluated, projected an average follow up of 6-8 years with significantly lower dislocation rates for DM cups. The total number of patients undergoing DM cup primary THA were 30,559 with an average age 71 years while the control group consisted of 218,834 patients with an average age of 69 years. DM group had lower rate of dislocation (p < 0.00001), total lower rate of cup revision (p < 0.00001, higher incidence of fracture (p>0.05).

DM THA is a viable alternative for conventional THA. The long-term results of DM cups in primary THA need to be further evaluated using high quality prospective studies and RCTs.

In a consecutive retrospective analysis of 190 patients treated with the Masquelet technique at the BG Klinikum Hamburg from January 2012 to January 2022, defect-specific features such as the extent and morphology of the defect were recorded, and their influence on the time to reach full weight-bearing of the affected limb was investigated.

A total of 217 defects were treated in 190 patients using the Masquelet technique. 70% of all defects were located in the tibia, followed by 22% in the femur and only about 7% in the upper extremity. The average length of all defects was 58 mm (+/−31 mm), with the largest defect measuring 180 mm and the smallest measuring 20 mm. 89% of the patients achieved full weight-bearing at the end of therapy. The average time from initiation of therapy to reaching safe full weight-bearing was 589 days. There was a significant correlation between defect length and time to reach full weight-bearing (p = 0.0134). These results could serve as a basis for creating a score for prognostics and evaluation of bone healing after treatment with the Masquelet technique. Additionally, the results could help guide indications for secondary stabilization using internal fixation.

Femoro-acetabular impingement involves a deformity of the hip joint and is associated with hip osteoarthritis. Although 15% of the asymptomatic population exhibits a deformity, it is not clear who will develop symptoms. Current diagnostic imaging measures have either low specificity or low sensitivity and do not consider the dynamic nature of impingement during daily activities. The goal of this study is to determine stresses in the cartilage, subchondral bone and labrum of normal and impinging hips during activities such as walking and sitting down.

Quantitative CT scans were obtained of a healthy Control and a participant with a symptomatic femoral cam deformity (‘Bump’). 3D models of the hip were created from automatic segmentation of CT scans. Cartilage layers were added so the articular surface was the mid-line of the joint. Finite element meshes were generated in each region. Bone elastic modulus was assigned element-by-element, calculated from CT intensity converted to bone mineral density using a calibration phantom. Cartilage was modelled as poroelastic, E=0.467 MPa, v=0.167, and permeability 3×10^-16 m⁴/N s. The pelvis was fixed while rotations and contact forces from Bergmann et al. (2001) were applied to the femur over one load cycle for walking and sitting in a chair. All analyses were performed in FEBio.

High shear stresses were seen near the acetabular cartilage-labrum junction in the Bump model, up to 0.12 MPa for walking and were much higher than in the Control.

Patient-specific modelling can be used to assess contact and tissue stresses during different activities to better understand the risk of degeneration in individuals, especially for activities that involve high hip flexion. The high stresses at the cartilage labrum interface could explain so-called bucket-handle tears of the labrum.

The management of comminuted metaphyseal fractures is a technical challenge and satisfactory outcomes of such fixations often remain elusive. The small articular fragments and bone loss often make it difficult for standard fixation implants for proper fixation. We developed a novel technique to achieve anatomical reduction in multiple cases of comminuted metaphyseal fractures at different sites by employing the cantilever mechanism with the help of multiple thin Kirschner wires augmented by standard fixation implants.

We performed a retrospective study of 10 patients with different metaphyseal fractures complicated by comminution and loss of bone stock. All patients were treated with the help of cantilever mechanism using multiple Kirschner wires augmented by compression plates. All the patients were operated by the same surgeon between November 2020 to March 2021 and followed up till March 2023. Surgical outcomes were evaluated according to the clinical and radiological criteria.

A total of 10 patients were included in the study. Since we only included patients with highly unstable and comminuted fractures which were difficult to fix with traditional methods, the number of patients in the study were less. All 10 patients showed satisfactory clinical and radiological union at the end of the study with good range of motion. One of the patient in the study had post-operative wound complication which was managed conservatively with regular dressings and oral antibiotics.

Comminuted metaphyseal fractures might differ in pattern and presentation with every patient and there can be no standard treatment for all. The cantilever technique of fracture fixation is based on the principle of cantilever mechanism used in bridges and helps achieve good anatomical reduction and fixation. It provides a decent alternative when standard modes of fixation don't give desired result owing to comminuted nature of fractures and deficiency of bone stock.

Primary bone tumors are rare, complex and highly heterogeneous. Its diagnostic and treatment are a challenge for the multidisciplinary team. Developments on tumor biomarkers, immunohistochemistry, histology, molecular, bioinformatics, and genetics are fundamental for an early diagnosis and identification of prognostic factors. The personalized medicine allows an effective patient tailored treatment. The bone biopsy is essential for diagnosis. Treatment may include systemic therapy and local therapy. Frequently, a limb salvage surgery includes wide resection and reconstruction with endoprosthesis, biological or composites. The risk for local recurrence and distant metastases depends on the primary tumor and treatment response.

Cancer patients are living longer and bone metastases are increasing. Bone is the third most frequently location for distant lesions. Bone metastases are associated to pain, pathological fractures, functional impairment, and neurological deficits. It impacts survival and patient quality of life. The treatment of metastatic disease is a challenge due to its complexity and heterogeneity, vascularization, reduced size and limited access. It requires a multidisciplinary treatment and depending on different factors it is palliative or curative-like treatment. For multiple bone metastases it is important to relief pain and increases function in order to provide the best quality of life and expect to prolong survival. Advances in nanotechnology, bioinformatics, and genomics, will increase biomarkers for early detection, prognosis, and targeted treatment effectiveness. We are taking the leap forward in precision medicine and personalized care.

To evaluate the therapeutic effect of Pulsed Electromagnetic Field (PEMF) in the treatment of meniscal tears in the avascular region.

Seventy-two twelve-week-old male Sprague-Dawley rats with full-thickness longitudinal medial meniscal tears in the avascular region were divided into 3 groups: control group (G_con), treated with classic signal PEMF (G_classic), and high slew rate signal PEMF(G_HSR). The HSR signal has the same pulse and burst frequencies as the classic signal, but with a higher slew rate. Macroscopic observation and histological analysis of the meniscus and articular cartilage were performed to evaluate the meniscal healing and progressions of osteoarthritis. The synovium was harvested for histological and immunofluorescent analysis to assess the intra-articular inflammation. The meniscal healing, articular cartilage degeneration, and synovitis were quantitatively evaluated according to their respective scoring system.

Dramatic degenerative changes of the meniscus and articular cartilage were noticed during gross observation and histological evaluation in the control group at 8 weeks. However, the menisci in the two treatment groups were restored to normal morphology with a smooth surface and shiny white color. Particularly, the HSR signal remarkably enhanced the fibrochondrogenesis and accelerated the remodeling process of the regenerated tissue. The meniscal healing scores of PEMF treatment groups were significantly higher than those in the control group at 8 weeks. Specifically, the HSR signal showed a significantly higher meniscal repair score than the classic signal at week 8 (P < .01). The degeneration score (G_con versus G_classic: P < .0001; Gcon versus G_HSR: P < .0001) and synovitis score (G_con versus Gclassic: P < .0001; G_con versus G_HSR: P = .0002) of the control groups were significantly higher than those in the two treatment groups.

PEMF promoted the healing of meniscal tears in the avascular region and restored the injured meniscus to its structural integrity in a rat model. Compared to the classic signal, the HSR signal showed the increased capability to promote fibrocartilaginous tissue formation and modulate the inflammatory environment and therefore protected the knee joint from post-traumatic osteoarthritis development.

The optimal treatment strategy for post-traumatic long bone non-unions is subject of an ongoing discussion. At the Maastricht University Medical Center (MUMC+) the induced membrane technique is used to treat post-traumatic long bone non-unions. This technique uses a multimodal treatment algorithm involving bone marrow aspirate concentrate (BMAC), the reamer-irrigator-aspirator (RIA) and P-15 bioactive peptide (iFactor, Cerapedics). Bioactive glass (S53P4 BAG, Bonalive) is added when infection is suspected. This study aims to objectify the effect of this treatment algorithm on the health-related quality of life (HRQoL) of patients with post-traumatic long bone non-unions. We hypothesized that HRQoL would improve after treatment.

From January 2020 to March 2023, consecutive patients who were referred to a multidisciplinary (trauma, orthopaedic and plastic surgery) non-union clinic at the MUMC+, The Netherlands, were evaluated using the Non-Union Scoring System (NUSS). The EQ-5D-5L questionnaire and the Lower Extremity Functional Scale (LEFS) were employed to obtain HRQoL outcomes both prior to and subsequent to surgery, with a follow-up at 6, 18 and 35 weeks.

Seventy-six patients were assessed at baseline (T0), with a mean NUSS of 40 (± 13 SD). Thirty-eight patients had their first follow-up, six weeks after surgery (T1). Thirty-one patients had a second follow-up at 18 weeks (T2), and twenty patients had the third follow-up at 35 weeks (T3). The EQ-5D index mean at baseline was 0.480, followed by an index of 0.618 at T1, 0.636 at T2, and 0.702 at T3. A significant difference was found in the HRQoL score between T0 and T1, as well as T2 and T3 (p<0.001; p=0.011). The mean LEFS significantly increased from 26 before intervention to 34, 39, and 43 after treatment (p<0.001; p=0.033; p=0.016).

This study demonstrated a significant improvement in the health-related quality of life of patients with post-traumatic long bone non-unions after the standardized treatment algorithm following the induced membrane technique.

Tendon injury is debilitating and recalcitrant. With limited knowledge of disease aitiology we have are lacking in effective treatments for this prevalent musculoskeletal complaint.

This presentation will outline our findings over the past few years in which we have demonstrated the importance of the interfascicular matrix (IFM) niche in maintaining healthy tendon function and driving disease progression^1,2. It will also continue to describe our progress in developing both in vivo and in vitro models to interrogate disease progression.

We have developed and validated a rat Achilles tendon overload model, in order to explore the impact of loading on IFM and fascicle structure, and the resulting cell response. Data highlights that structural disruption and inflammatory response both initiate in the IFM region, and can be seen in the absence of demonstrable changes to animal gait, indicating a sub-injury response in the tendon which we hypothesis may drive increased matrix turnover and repair³.

We are now looking to interrogate the pathways driving this inflammatory behaviour in an organ-chip model, exploring the interplay between IFM cells and cells within fascicles. We have demonstrated phenotypic distinction of cells from the two niche environments, localized the progenitor phenotype to the IFM region and demonstrated significant mechanosensitivity in the IFM cell population⁴. We are currently building appropriate niche environments to maintain cell phenotype in our in vitro models, to explore the metabolic changes associated with disease progression.

Acknowledgements: This body of work has received funding from: BBSRC (BB/K008412 /1); Versus Arthritis (project grant 20262); Horserace Betting Levy Board (T5); Dunhill Medical Charity (project grant RPGF1802\23); MRC (MR/T015462/1).

The covid-19 pandemic had a great impact in the daily clinical and surgical practice. Concerning patients with a femoral neck fracture, there is the need of a negative Sars-CoV-2 test or an established isolation period for the positive cases, pre-operatively. The goal of this study was to evaluate the impact of the pandemic in the management of patients with femoral neck fractures, who were submitted to surgical treatment with hemiarthroplasty, in our hospital.

A retrospective, observational study was performed, analysing the patients with femoral neck fractures submitted to hip hemiarthroplasty, during the years 2019 (before the pandemic) and 2020 (first year of the pandemic). We analysed the first 5 patients operated in each month of the mentioned years.

We analysed 56 and 60 patients submitted to surgery in the years 2019 and 2020, respectively. The inpatient days were, in average, 14.1 and 13.1. Patients were operated, in average, 3.0 and 3.8 days after admission (corrected to 2.5 and 3.6 days if the time of discontinuation of anticoagulants or antiplatelets needed before surgery is deducted). There were peri-operative complications in 53.6% and 46.7% of the patients, in 2019 and 2020 respectively. The most common complication in both groups was a low postoperative haemoglobin level needing red blood cell transfusion. One-year postoperative mortality rate was 17.9% and 13.3%, respectively.

Despite the changes triggered by the new pandemic, there was an overall maintenance of the quality of the management of these patients, with only a slight increase in the interval between admission and surgery. Some of the remaining variables even showed an improvement when comparing the two groups of patients. Nevertheless, it is important to mention that there were patients infected with Covid-19 who died before being submitted to surgery, therefore not being present in these statistics.

To compare the efficacy of intra-articular and intravenous modes of administration of tranexamic acid in primary total knee arthroplasty in terms of blood loss and fall in haemoglobin level.

Study Design: Randomized controlled trial.

Duration of Study: Six months, from May 2019 to Nov 2019.

Seventy-eight patients were included in the study. All patients undergoing unilateral primary total knee replacement were included in the study. Exclusion criteria were patients with hepatitis B and C, history of previous knee replacement, bilateral total knee replacement, allergy to TXA, Hb less than 11g/dl in males and less than 10g/dl in females, renal dysfunction, use of anticoagulants for 7 days prior to surgery and history of thromboembolic diseases. Patients were randomly divided into group A and B. Group A patients undergoing unilateral primary total knee replacement (TKR) were given intravenous tranexamic acid (TXA) while group B were infiltrated with intra-articular TXA. Volume of drain output, fall in haemoglobin (Hb) level and need for blood transfusion were measured immediately after surgery and at 12 and 24 hours post operatively in both groups.

The study included 35 (44.87%) male and 43 (55.13%) female patients. Mean age of patients was 61 ± 6.59 years. The mean drain output calculated immediately after surgery in group A was 45.38 ± 20.75 ml compared with 47.95 ± 23.86 ml in group B (p=0.73). At 24 hours post operatively, mean drain output was 263.21 ± 38.50 ml in intravenous group versus 243.59 ± 70.73 ml in intra-articular group (p=0.46). Regarding fall in Hb level, both groups showed no significant difference (p>0.05). About 12.82% (n=5) patients in group A compared to 10.26% (n=4) patients required blood transfusion post operatively (p=0.72).

Intra-articular and intravenous TXA are equally effective in patients undergoing primary total knee arthroplasty in reducing post-operative blood loss.

For many years, marker-based systems have been used for motion analysis. However, the emergence of new technologies, such as 4D scanners provide exciting new opportunities for motion analysis. In 4D scanners, the subjects are measured as a dense mesh, which enables the use of shape analysis techniques. In this talk, we will explore how the combination of the rising new motion analysis methods and shape modelling may change the way we think about movement and its analysis.

The concept of guided growth was proposed by Andry in 1741. In the last decades the concept has been widely used as implants has been introduced that can modulate the growth of the bone and pediatric longitudinal and angular deformities is widely treated by this technique. However, there is there is a huge variation in techniques and implants used and high-quality clinical trials is still lacking. Recently implants correcting rotational bony deformities have been proposed and clinical case series have been published.

The current status of guided growth will be presented in this narrative review and preliminary experiences with rotational guided growth will be shared. Is guided growth to be considered a safe treatment at this time point?

Syndesmotic ankle lesions involve disruption of the osseous tibiofibular mortise configuration as well as ligamentous structures stabilizing the ankle joint. Incomplete diagnosis and maltreatment of these injuries is frequent, resulting in chronic pain and progressive instability thus promoting development of ankle osteoarthritis in the long term. Although the pathogenesis is not fully understood, abnormal mechanics has been implicated as a principal determinant of ankle joint degeneration after syndesmotic ankle lesions. Therefore, the focus of this presentation will be on our recent development of a computationally efficient algorithm to calculate the contact pressure distribution in patients with a syndesmotic ankle lesion, enabling us to stratify the risk of OA development in the long term and thereby guiding patient treatment.

Critical size bone defects are frequently caused by accidental trauma, oncologic surgery, and infection. Distraction osteogenesis (DO) is a useful technique to promote the repair of critical size bone defects. However, DO is usually a lengthy treatment, therefore accompanied with increased risks of complications such as infections and delayed union.

Herein, we developed an innovative intramedullary biodegradable magnesium (Mg) nail to accelerate bone regeneration in critical size bone defect repair during DO.

We observed that Mg nail induced almost 4-fold increase of new bone formation and over 5-fold of new vessel formation at 2 weeks after distraction. Mg nail upregulated the expression of calcitonin gene-related peptide (CGRP) in the new bone as compared with the DO alone group. We further revealed that blockade of the sensory nerve by overdose capsaicin blunted Mg nail enhanced critical size bone defect repair during the DO process. Moreover, inhibitors/antagonist of CGRP receptor, FAK, and VEGF receptor blocked the Mg nail stimulated vessel and bone formation.

In summary, we revealed, for the first time, a CGRP-FAK-VEGF signaling axis linking sensory nerve and endothelial cells, which may be the main mechanism underlying Mg-enhanced critical size bone defect repair when combined with DO, suggesting a great potential of Mg implants in reducing DO treatment time for clinical applications.

Patients who are Jehovah's witnesses do not accept blood transfusions. Thus, total hip arthroplasty can be challenging in this group of patients due to the potential for blood loss. Multiple strategies have been developed in order to prevent blood loss.

A 76-year-old female, Jehovah's witness medicated with a platelet antiaggregant, presented to the emergency department after a fall from standing height. Clinically, she had pain mobilizing the right lower limb and radiological examination revealed an acetabular fracture with femoral head protrusion and ipsilateral isquiopubic fracture. Skeletal traction was applied to the femur during three weeks and no weight bearing was maintained during the following weeks. Posteriorly, there was an evolution to hip osteoarthritis with necrosis of the femoral head.

The patient was submitted to surgery six months after the initial trauma, for a total hip arthroplasty. The surgery was performed with hypotensive anaesthesia, careful surgical technique and meticulous haemostasis and there was no need for blood transfusion. Posteriorly, there was a positive clinical evolution with progressive improvement on function and deambulation.

Total hip arthroplasty may be safely carried out with good clinical outcomes in Jehovah's witnesses, without the need for blood transfusion, if proper perioperative precautions are taken, as has already been shown in previous studies.

The aim is to investigate if there is a relation between patellar height and knee flexion angle. For this purpose we retrospectively evaluated the radiographs of 500 knees presented for a variety of reasons.

We measure knee flexion angle using a computer-generated goniometer. Patellar height was determined using computer generated measurement for the selected ratios, namely, the Insall–Salvati (I/S), Caton–Deschamps (C/D) and Blackburne–Peel (B/P) indices and Modified I/S Ratio.

A search of an NHS hospital database was made to identify the knee x rays for patients who were below the age of forty. A senior knee surgeon (DC) supervised three trainee trauma and orthopaedics doctors (HA, JM, ES) working on this research. Measurements were made on the Insall–Salvati (I/S), Caton–Deschamps (C/D) and Blackburne–Peel (B/P) indices and Modified I/S Ratio. The team leader then categorised the experimental measurement of patients’ knee flexion angle into three groups. This categorisation was according to the extent of knee flexion. The angles were specifically, 10.1 to 20, 20.1 to 30, and 30.1 to 40 degrees of knee flexion.

Out of the five-hundred at the start of the investigation, four hundred and eighteen patients were excluded because they had had either an operation on the knee or traumatic fracture that was treated conservatively.

Medial opening wedge high tibial osteotomy (MOWHTO) is the workhorse procedure for correcting varus malalignment of the knee. There have been recent developments in the synthetic options to fill the osteotomy gap. The current gold standard for filling this osteotomy gap is autologous bone graft which is associated with donor site morbidity. We would like to introduce and describe the process of utilizing the novel Osteopore® 3D printed, honeycomb structured, Polycaprolactone and β-Tricalcium Phosphate wedge for filling the gap in MOWHTO. In the advent of additive manufacturing and the quest for more biocompatible materials, the usage of the Osteopore® bone wedge in MOWHTO is a promising technique that may improve the biomechanical stability as well the healing of the osteotomy gap.

We developed a novel silorane-based biomaterial (SBB) for use as an orthopedic cement. SBB is comprised of non-toxic silicon-based monomers, undergoes non-exothermic polymerization, and has weight-bearing strength required of orthopedic cements. We sought to compare the antibiotic release kinetics of this new cement to that of commercially available PMMA bone cement. We also evaluated each material's inherent propensity to support the attachment of bacteria under both static and dynamic conditions.

One gram of either rifampin or vancomycin was added to 40g batches of PMMA and SBB. Pellets were individually soaked in PBS. Eluate was collected and tested daily for 14 days using HPLC. Compressive strength and modulus were tested over 21 days. Bioassays were used to confirm the bioactivity of the antibiotics eluted.

We measured the growth and maturation of staphylococcus aureus (SA) biofilm on the surface of both PMMA and SBB disks over the course of 72 hours in a static well plate and in a dynamic biofilm reactor (CDC Biofilm Reactor). N=4 at 24, 48, and 72 hours. A luminescent strain of SA (Xen 29) was employed allowing imaging of bacteria on the discs.

SBB eluted higher concentrations of vancomycin than did PMMA over the course of 14 days (p<0.001). A significant 55.1% greater day 1 elution was observed from SBB. Silorane cement was able to deliver rifampin in clinically favorable concentrations over 14 days. On the contrary, PMMA was unable to deliver rifampin past day 1. The incorporation of rifampin into PMMA severely reduced its mechanical strength (p<0.001) and modulus (p<0.001).

Surface bacterial radiance of PMMA specimens was significantly greater than that of SBB specimens at all time points (p<0.05).

The novel silorane-based cement demonstrated superior antibiotic release and, even without antibiotic incorporation, demonstrated an innate inhabitation to bacterial attachment and biofilm.

The primary aim of this study was to compare the clinical outcomes of osteoid osteoma (OO) between the group of patients with the presence of nidus on biopsy samples from radiofrequency ablation (RFA) with those without nidus. Secondly, we aimed to examine other factors that may affect the outcomes of OO reflecting our experience as a tertiary orthopaedic oncology centre.

We retrospectively reviewed 88 consecutive patients diagnosed with OO treated with RFA between November 2005 and March 2015, consisting of 63 males (72%) and 25 females (28%). Sixty-six patients (75%) had nidus present in their biopsy samples. Patients’ mean age was 17.6 years (4-53). Median duration of follow-up was 12.5 months (6-20.8). Lesions were located in the appendicular skeleton in seventy-nine patients (90%) while nine patients (10%) had an OO in the axial skeleton. Outcomes assessed were based on patients’ pain alleviation (partial, complete, or no pain improvement) and the need for further interventions.

Pain improvement in the patient group with nidus in histology sample was significantly better than the group without nidus (OR 7.4, CI 1.35-41.4, p=0.021). The patient group with nidus on biopsy demonstrated less likelihood of having a repeat procedure compared to the group without nidus (OR 0.092, CI 0.016-0.542, p=0.008). Our study showed significantly better outcomes in pain improvement in appendicular lesions compared to the axially located lesions (p = 0.005). Patients with spinal lesions tend to have relatively poor pain relief than those with appendicular or pelvic lesions (p=0.007).

Patients with nidus on histology had better pain alleviation compared to patients without nidus. The histological presence of nidus significantly reduces the chance of repeat interventions. The pain alleviation of OO following RFA is better in patients with appendicular lesions than spinal or axially located lesions.

The clinical success of osteochondral autografts is heavily reliant on their mechanical stability, as grafts which protrude above or subside below the native cartilage can have a negative effect on the tribological properties of the joint [1]. Furthermore, high insertion forces have previously been shown to reduce chondrocyte viability [2]. Commercial grafting kits may include a dilation tool to increase the diameter of the recipient site prior to insertion. The aim of this study was to evaluate the influence of dilation on the primary stability of autografts.

Six human cadaveric femurs were studied. For each femur, four 8.5 × 8mm autografts were harvested from the trochlear groove and implanted into the femoral condyles using a Smith & Nephew Osteochondral grafting kit. Two grafts were implanted into dilated recipient sites (n=12) and two were implanted with no dilation (n=12). Insertion force was measured by partially inserting the graft and applying a load at a rate of 1 mm/min, until the graft was flush with the surrounding cartilage. Push-in force was measured by applying the same load, until the graft had subsided 4mm below congruency. Significance was taken as (p<0.05).

Average maximum insertion force of dilated grafts was significantly lower (p<0.001) than their non-dilated equivalent [28.2N & 176.7N respectively]. There was no significant difference between average maximum push-in force between the dilated and non-dilated groups [1062.8N & 1204.2N respectively].

This study demonstrated that significantly less force is required to insert dilated autografts, potentially minimising loss of chondrocyte viability. However, once inserted, the force required to displace the grafts below congruency remained similar, indicating a similar degree of graft stability between both groups.

To design slow resorption patient-specific bone graft whose properties of bone regeneration are increased by its geometry and composition and to assess it in in-vitro and in-vivo models.

A graft composed by hydroxyapatite (HA) and β-TCP was designed as a cylinder with 3D gyroid porosities and 7 mm medullary space based on swine's anatomy. It was produced using a stereolithography 3D-printing machine (V6000, Prodways).

Sterile bone grafts impregnated with or without a 10µg/mL porcine BMP-2 (pBMP-2) solution were implanted into porcine femurs in a bone loss model. Bone defect was bi-weekly evaluated by X-ray during 3 months. After sacrifice, microscanner and non-decalcified histology analysis were conducted on biopsies.

Finally, osteoblasts were cultured inside the bone graft or in monolayer underneath the bone graft. Cell viability, proliferation, and gene expression were assessed after 7 and 14 days of cell culture (n=3 patients).

3D scaffolds were successfully manufactured with a composition of 80% HA and 20% β-TCP ±5% with indentation compressive strength of 4.14 MPa and bending strength of 11.8MPa.

In vivo study showed that bone regeneration was highly improved in presence of pBMP-2. Micro-CT shows a filling of the gyroid sinuses of the implant (Figure 1).

In vitro, the presence of BMP2 did not influence the viability of the osteoblasts and the mortality remained below 3%. After 7 days, the presence of BMP2 in the scaffold significantly increased by 85 and 65% the COL1A1 expression and by 8 and 33-fold the TNAP expression by osteoblasts in the monolayer or in the scaffold, respectively. This BMP2 effect was transient in monolayer and did not modify gene expression at day 14.

BMP2-impregnated bone graft is a promising patient-personalized 3D-printed solution for bone defect regeneration, by promoting neighboring host cells recruitment and solid new bone formation.

For any figures and tables, please contact the authors directly.

High tibial osteotomy (HTO) is a joint preserving alternative to knee replacement for medial tibiofemoral osteoarthritis in younger, more active patients. The procedure is technically challenging and limited also by ‘one size fits all’ plates which can result in patient discomfort necessitating plate removal.

This clinical trial evaluated A novel custom-made HTO system – TOKA (3D Metal Printing LTD, Bath, UK) for accuracy of osteotomy correction and improvements in clinical outcome scores.

The investigation was a single-arm single-centre prospective clinical trial (IRCCS Istituto Ortopedico Rizzoli; ClinicalTrials.gov NCT04574570), with recruitment of 25 patients (19M/6F; average age: 54.4 years; average BMI: 26.8), all of whom received the TOKA HTO 3D planning and surgery. All patients were predominantly diagnosed with isolated medial knee osteoarthritis and with a varus deformity under 20°. Patients were CT scanned pre- and post-operatively for 3D virtual planning and correctional assessment. All surgeries were performed by the lead clinical investigator – a consultant knee surgeon with a specialist interest in and clinical experience of HTO.

On average, Knee Society Scores (KSS) improved significantly (p<0.001) by 27.6, 31.2 and 37.2 percentage points respectively by 3-, 6- and 12-months post-surgery respectively. Other measures assessed during the study (KOOS, EQ5D) produced similar increases.

Our early experience using custom implants is extremely promising. We believe the reduced profile of the plate, as well as the reduced invasiveness and ease of surgery contributed to faster patient recovery, and improved outcome scores compared to conventional techniques. These clinical outcome results compare very favourably other case-series with published KOOS scores using different devices.

Previous research has shown catabolic cell signalling induced by TNF-α and IL-1β within intervertebral (IVD) cells. However, these studies have investigated this in 2D monolayer cultures, and under hyper-physiological doses. Thus, we aim to revisit the catabolic responses of bovine IVD cells in vitro in 3D culture under increasing doses of TNF-α or IL-1β stimulation at three different timepoints.

Primary bovine nucleus pulposus (NP) and annulus fibrosus (AF) cells were isolated and expanded for two weeks. Subsequently, NP and AF cells were encapsulated in 1.2% alginate beads (4 × 106 cells/ml) and cultured for two weeks for phenotype recovery. Re-differentiated cells were stimulated with 0.1, 1 and 10 ng/ml TNF-α or with 0.01, 0.1 and 10 ng/ml IL-1β for one week. Beads were collected on the stimulation day (Day 0) and on Day 1 and 7 after stimulation.

A dose-dependent upregulation of catabolic markers was observed in both cell types after one day of TNF-α or IL-1β stimulation. 10 ng/ml TNF-α stimulation induced a significant upregulation (p<0.05) of ADAMTS4, MMP3 and MMP13 in AF cells after one day of stimulation. Similarly, MMP3 upregulation showed a strong trend (p=0.0643) in NP cells. However, no effects on expression were seen after seven days. In addition, no significant difference between treatments in COL2, COL1 and ACAN expression was observed, and cell viability was not reduced at any time point, regardless of the treatment.

We demonstrate a dose-dependent upregulation of catabolic markers in NP and AF cells under TNF-α or IL-1β stimulation, with a significant upregulation of ADAMTS4, MMP3 and MMP13 genes in AF cells after one day of treatment. Notably, after seven days of treatment, the dose-dependent effects were no longer observed possibly due to an adaptation mechanism of IVD cells to counter the metabolic shift.

Matrix metalloproteinase enzymes (MMPs) play a crucial role in the remodeling of articular cartilage, contributing also to osteoarthritis (OA) progression. The pericellular matrix (PCM) is a specialized space surrounding each chondrocyte, containing collagen type VI and perlecan. It acts as a transducer of biomechanical and biochemical signals for the chondrocyte. This study investigates the impact of MMP-2, -3, and -7 on the integrity and biomechanical characteristics of the PCM.

Human articular cartilage explants (n=10 patients, ethical-nr.:674/2016BO2) were incubated with activated MMP-2, -3, or -7 as well as combinations of these enzymes. The structural degradative effect on the PCM was assessed by immunolabelling of the PCM's main components: collagen type VI and perlecan. Biomechanical properties of the PCM in form of the elastic moduli (EM) were determined by means of atomic force microscopy (AFM), using a spherical cantilever tip (2.5µm).

MMPs disrupted the PCM-integrity, resulting in altered collagen type VI and perlecan structure and dispersed pericellular arrangement. A total of 3600 AFM-measurements revealed that incubation with single MMPs resulted in decreased PCM stiffness (p<0.001) when compared to the untreated group. The overall EM were reduced by ∼36% for all the 3 individual enzymes. The enzyme combinations altered the biomechanical properties at a comparable level (∼36%, p<0.001), except for MMP-2/-7 (p=0.202).

MMP-induced changes in the PCM composition have a significant impact on the biomechanical properties of the PCM, similar to those observed in early OA. Each individual MMP was shown to be highly capable of selectively degrading the PCM microenvironment. The combination of MMP-2 and -7 showed a lower potency in reducing the PCM stiffness, suggesting a possible interplay between the two enzymes. Our study showed that MMP-2, -3, and -7 play a direct role in the functional and structural remodeling of the PCM.

Acknowledgements: This work was supported by the Faculty of Medicine of the University of Tübingen (grant number.: 2650-0-0).

Cell-based therapies offer a promising strategy to treat tendon injuries and diseases. Both mesenchymal stromal cells (MSCs) and pluripotent stem cells (PSCs) are good candidates for such applications due to their self-renewing and differentiation capacity. However, the translation of cell-based therapies from bench to bedside can be hindered by the use of animal-derived components in ancillary materials and by the lack of standardised media and protocols for in vitro tenogenic differentiation. To address this, we have optimized animal component-free (ACF) workflows for differentiating human MSCs and PSCs to tenocyte-like cells (TLCs) respectively. MSCs isolated from bone marrow (n = 3) or adipose tissue (n = 3) were expanded using MesenCult™-ACF Plus Culture Kit for at least 2 passages, and differentiated to TLCs in 21 days using a step-wise approach. Briefly, confluent cultures were treated with an ACF tenogenic induction medium for 3 days, followed by treatment with an ACF maturation medium for 18 days. Monolayer cultures were maintained at high density without passaging for the entire duration of the protocol, and the medium was changed every 2 – 3 days. In a similar fashion, embryonic (n = 3) or induced PSCs (n = 3) were first differentiated to acquire a mesenchymal progenitor cell (MPC) phenotype in 21 days using STEMdiff™ Mesenchymal Progenitor Kit, followed by the aforementioned tenogenic protocol for an additional 21 days. In all cases, the optimized workflows using ACF formulations consistently activated a tenogenic transcriptional program, leading to the generation of elongated, spindle-shaped tenomodulin-positive (TNMD+) cells and deposition of an extracellular matrix predominantly composed of collagen type I. In summary, here we describe novel workflows that can robustly generate TLCs from MSCs and hPSC-derived MPCs for potential translational applications.

Establishing disease biomarkers has been a long-sought after goal to improve Osteoarthritis (OA) diagnosis, prognosis, clinical and pharmaceutical interventions. Given the role of the synovium in contributing to OA, a meta-analysis was performed to determine significant synovial biomarkers in human OA tissue, compared to non-OA patients. Outcomes will direct future research on marker panels for OA disease modelling in vitro/in vivo, aiding clinical research into OA disease targets.

A PRISMA compliant search of databases was performed to identify potential biomarker studies analysing human, OA, synovial samples compared to non-OA/healthy participants. The Risk of Bias In Non-Randomised Studies of Interventions (ROBINS-I) tool assessed methodological quality, with outcome analysed by Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were conducted for individual biomarkers using fixed or random effect models, as appropriate. Where three or more studies included a specific biomarker, Forest Plot comparisons were generated.

3230 studies were screened, resulting in 34 studies encompassing 25 potential biomarkers (1581 OA patients and 695 controls). Significant outcomes were identified for thirteen comparisons. Eleven favoured OA (IL-6, IL-10, IL-13, IP-10, IL-8, CCL4, CCL5, PIICP, TIMP1, Leptin and VEGF), two favoured non-OA controls (BMP-2 and HA). Notably, PIICP showed the largest effect (SMD 6.11 [3.50, 8.72], p <0.00001, I² 99%), and TIMP1 resulted critically important (0.95 [0.65, 1.25], p <0.00001, I² 82%). Leptin and CCL4 showed lower effects (SMD 0.81 [0.33, 1.28], p =0.0009; 0.59 [0.32, 0.86], p <0.0001, respectively).

Thirteen significant synovial biomarkers showed links with OA bioprocesses including collagen turnover, inflammatory mediators and ECM components. Limitations arose due to bias risk from incomplete or missing data, publication bias of inconclusive results, and confounding factors from patient criteria. These findings suggest markers of potential clinical viability for OA diagnosis and prognosis that could be correlated with specific disease stages.

Tibial periprosthetic fracture is an important complication of the Oxford Unicompartmental Knee Replacement (OUKR). Primary fixation of cementless OUKR tibial components relies on the interference-fit of the ‘keel’ and a slot in the proximal tibia. Clinically used double blade keel saws (DKS) create slots with two grooves, generating stress concentrations where fractures may initiate. This study aimed to investigate slot factors that may influence incidence of tibial periprosthetic fractures.

Slots were made in PCF20 polyurethane foam using the DKS plus/minus adjuvant rasping, single blade keel saw (SKS), and rasp-only. Round and square slots were machined with milling cutters. Compact tensile tests were conducted per ASTM E399 to determine tensile load to fracture (TLTF) and results were validated using bovine tibia. Cementless OUKR components were implanted into slots in custom polyurethane blocks and compressed to failure to determine anatomical load to fracture (ALTF). A custom MATLAB program calculated slot roundness from cross-sectional images.

Round slots had higher TLTF (29.5N, SD=2.7) than square (25.2N, SD=1.7, p<0.05) and DKS slots (23.3N, SD=2.7, p<0.0001). Fractures occurred at the round slot apices, square slot corners, and deepest DKS slot grooves. ALTF was not significantly different between square and round slots. Adjuvant rasping made DKS slots significantly rounder, resulting in significantly higher TLTF, but rasping did not increase ALTF. ALTF was significantly higher for SKS (850N, SD=133, p<0.01) and rasp-only (912N, SD=100, p<0.001) slots compared to standard DKS slots (703N, SD=81).

Round keel slots minimise stress concentrations and increase TLTF but do not increase ALTF. The SKS and rasp-only slots retain material at slot ends and have significantly higher ALTF. Future studies should assess saw blades that retain material and round slot ends to evaluate if their use may significantly reduce the incidence of tibial periprosthetic fracture.

For chondral damage in younger patients, surgical best practice is microfracture, which involves drilling into the bone to liberate the bone marrow. This leads to a mechanically inferior fibrocartilage formed over the defect as opposed to the desired hyaline cartilage that properly withstands joint loading. While some devices have been developed to aid microfracture and enable its use in larger defects, fibrocartilage is still produced and there is no clear clinical improvement over microfracture alone in the long term. Our goal is to develop 3D printed devices, which surgeons can implant with a minimally invasive technique. The scaffolds should match the functional properties of cartilage and expose endogenous marrow cells to suitable mechanobiological stimuli in-situ, in order to promote healing of articular cartilage lesions before they progress to osteoarthritis, and rapidly restore joint health and mobility. Importantly, scaffolds should direct a physiological host reaction, instead of a foreign body reaction, associated with chronic inflammation and fibrous capsule formation, negatively influencing the regenerative outcome.

Our novel silica/polytetrahydrofuran/polycaprolactone hybrids were prepared by sol-gel synthesis and scaffolds were 3D printed by direct ink writing. 3D printed hybrid scaffolds with pore channels of ~250 µm mimic the compressive behaviour of cartilage. Our results show that these scaffolds support human bone marrow stem/stromal cell (hMSC) differentiation towards chondrogenesis in vitro under hypoxic conditions to produce markers integral to articular cartilage-like matrix evaluated by immunostaining and gene expression analysis. Macroscopic and microscopic evaluation of subcutaneously implanted scaffolds in mice showed that scaffolds caused a minimal resolving inflammatory response. Our findings show that 3D printed hybrid scaffolds have the potential to support cartilage regeneration.

Acknowledgements: Authors acknowledge funding provided by EPSRC grant EP/N025059/1.

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.

Abstract

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Abstract

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.

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.

Abstract

Abstract

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.

Abstract

Abstract

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.

Abstract

To analyze the dynamics of the thoracic spine during deep breathing in AIS patients and in healthy matched controls.

Case-control cross-sectional study. 20 AIS patients (18 girls, Cobb angle, 54.7±7.9°; Risser 1.35±1.2) and 15 healthy volunteers (11 girls) matched in age (12.5 versus 15.8 yr. mean age) were included. In AIS curves, the apex was located in T8 (14) and T9 (6). Conventional sagittal radiographs of the whole spine were performed at maximal inspiration and expiration. The ROM of each spinal thoracic functional segment (T1-T7, T7-T10, T10-T12), the global T1–T12 ROM were measured. Respiratory function was assess by forced vital capacity (FVC), expiratory volume (FEV1), FEV1/FVC, inspiratory vital capacity (IVC) and peak expiratory flow (PEF).

In healthy subjects, the mean T1–T12 ROM during forced breathing was 16.7±3.8. AIS patients showed a T1-T12 ROM of 1.1±1.5 (p<0.05) indicating a sagittal stiffness of thoracic spine. A wide T7–T10 ROM (15.3±3.0) was found in healthy controls (91.6% of the T1–T12 ROM). AIS patients showed only 0.4±1.4 ROM at T7-T10 (36.4% of the T1–T12 ROM) (p<0.001). There was a significant correlation between T7-T10 ROM and IVC.

Lenke 1A AIS patients show a restriction of the thoracic spine motion with an almost complete abolition of T7-T10 ROM, a crucial segment participating in the deep breathing. T7-T10 stiffness could explain the ventilatory limitations found in AIS patients.

Decellularised porcine superflexor tendon (pSFT) has been demonstrated to be a suitable scaffold for anterior cruciate ligament reconstruction[1]. While the role of collagen in tendons is well known, the mechanical role of glycosaminoglycans (GAGs) is less clear and may be altered by the decellularisation process.

To determine the effects of decellularisation on pSFT GAG content and mechanical function and to investigate the consequences of GAG loss in tensile and compressive loading.

pSFTs were decellularised following previous techniques [2]. For GAG removal, native pSFTs were treated with chondroitinase ABC (ChABC; 0.1U/mL, 72h). Cell and GAG removal was validated using histology and quantitative assays. Native, decellularised and ChABC treated groups (n=6) were biomechanically characterised. In tension, specimens underwent stress relaxation and strength testing using previous protocols [1]. Stress relaxation data was fitted to a modified Maxwell-Weichert model to determine time-dependent (E1 & E2) and time-independent moduli (E0). The toe and linear region moduli (Etoe, Elinear), in addition to tensile strength (UTS) and failure strain were determined from strength testing. In compression, specimens underwent confined loading conditions (ramp at 10 s-1 to 10% strain and hold). The aggregate modulus (HA) and zero-strain permeability (k0) were determined using previous techniques [3]. Data was analysed by one-way ANOVA with Tukey post-hoc test to determine significant differences between test groups (p<0.05).

Quantitative assays showed no GAG reduction post-decellularisation, but a significant reduction after ChABC treatment. HA was only significantly reduced in the ChABC group. k0 was significantly higher for the ChABC group compared to decellularised. E0 was significantly reduced in the decellularised group compared to native and ChABC groups, while E1 and E2 were not different between groups. Etoe, Elinear, UTS and failure strain were not different between groups.

Decellularisation does not affect GAG content or impair mechanical function in pSFT. GAG loss adversely affects pSFT compressive properties, revealing major mechanical contribution under compression, but no significant role under tension.

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.

Tendinopathy is a disease associated with pain and tendon degeneration, leading to a decreased range of motion and an increased risk of tendon rupture. The etiology of this frequent disease is still unknown. In other musculoskeletal tissues like cartilage and intervertebral discs, transient receptor potential channels (TRP- channels) were shown to play a major role in the progression of degeneration. Due to their responsiveness to a wide range of stimuli like temperature, pH, osmolarity and mechanical load, they are potentially relevant factors in tendon degeneration as well. We therefore hypothesize that TRP- channels are expressed in tendon cells and respond to degeneration inducing stimuli.

By immunohistochemistry, qRT-PCR and western blot analyses, we found three TRP channel members, belonging to the vanilloid (TRPV), and ankyrin (TRPA) subfamily, respectively, to be expressed in healthy human tendon tissue as well as in rodent tendon, with expression being located to cells within the dense tendon proper, as well as to endotenon resident cells. In vitro-inflammatory and ex vivo-mechanical stimulation led to a significant upregulation of TRPA1 expression in tendon cells, which correlates well with the fact that TRPA1 is considered as mechanosensitive channel being sensitized by inflammatory mediators.

This is the first description of TRP- channels in human and rodent tendon. As these channels are pharmacologically targetable by both agonists and antagonists, they may represent a promising target for novel treatments of tendinopathy.

This study examined pre-operative measures to predict post-operative biomechanical outcomes in total knee arthroplasty (TKA) patients.

Twenty-eight patients (female=12/male=16, age=63.6±6.9, BMI=29.9±7.4 kg/m2) with knee osteoarthritis scheduled to undergo TKA were included. All surgeries were performed by the same surgeon (GD) with a subvastus approach. Patients visited the gait lab within one-month prior to surgery and 12 months following surgery. At the gait lab, patients completed the knee injury and osteoarthritis outcome score (KOOS), a timed up and go (TUG), maximum knee flexion and extension strength evaluation, and a walking task. Variables of interest included the five KOOS sub-scores, TUG time, maximum knee flexion and extension strength normalized to body weight, walking speed, and peak knee biomechanics variables (flexion angle, abduction moment, power absorption). A Pearson's correlation was used to identify significantly correlated variables which were then inputted into a multiple regression.

No assumption violations for the multiple regression existed for any variables. Pre-operative knee flexion and extension strength, TUG time, and age were used in the multiple regression. The multiple regression model statistically significantly predicted peak knee abduction moment, post-operative walking speed, and post-operative knee flexion strength. All four variables added statistically significantly to the prediction p<.05.

Pre-operative KOOS values did not correlate with any biomechanical indicators of post-operative success. Age, pre-operative knee flexion and extension strength, and TUG times predicted peak knee abduction moment, which is associated with medial knee joint loading. These findings stress the importance of pre-surgery condition, as stronger individuals achieved better post-operative biomechanical outcomes. Additionally, younger patients had better outcomes, suggesting that surgeons should not delay surgery in younger patients. This delay in surgery may prevent patients from achieving optimal outcomes. Future studies should utilize a hierarchical multiple regression to identify which variables are most predictive.

Total temporomandibular joint (TMJ) replacements reduce pain and improve quality of life in patients suffering from end-stage TMJ disorders, such as osteoarthritis and trauma. Jaw kinematics measurements following TMJ arthroplasty provide a basis for evaluating implant performance and jaw function. The aim of this study is to provide the first measurements of three-dimensional kinematics of the jaw in patients following unilateral and bilateral prosthetic TMJ surgeries.

Jaw motion tracking experiments were performed on 7 healthy control participants, 3 unilateral and 1 bilateral TMJ replacement patients. Custom-made mouthpieces were manufactured for each participant's mandibular and maxillary teeth, with each supporting three retroreflective markers anterior to the participant's lip line. Participants performed 15 trials each of maximum jaw opening, lateral and protrusive movements. Marker trajectories were simultaneously measured using an optoelectronic tracking system. Laser scans taken of each dental plate, together with CT scans of each patient, were used to register the plate position to each participant's jaw geometry, allowing 3D condylar motion to be quantified from the marker trajectories.

The maximum mouth opening capacity of joint replacement patients was comparable to healthy controls with average incisal inferior translations of 37.5mm, 38.4mm and 33.6mm for the controls, unilateral and bilateral joint replacement patients respectively. During mouth opening the maximum anterior translation of prosthetic condyles was 2.4mm, compared to 10.6mm for controls. Prosthetic condyles had limited anterior motion compared to natural condyles, in unilateral patients this resulted in asymmetric opening and protrusive movements and the capacity to laterally move their jaw towards their pathological side only. For the bilateral patient, protrusive and lateral jaw movement capacity was minimal.

Total TMJ replacement surgery facilitates normal mouth opening capacity and lateral and inferior condylar movements but limits anterior condylar motion. This study provides future direction for TMJ implant design.

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.

Chronic lateral ankle instability (CLAI) is treated operatively, whereas acute ligament injury is usually treated nonoperatively. Such treatments have been widely validated. Apoptosis is known to cause ligament degeneration; however, few reports have focused on the possible role of apoptosis in degeneration of ruptured lateral ankle ligaments. The aim of our study is to elucidate the apoptosis that occurs within anterior talofibular ligament (ATFL) to further validate current CLAI treatments by adducing molecular and cellular evidence.

Between March 2019 and February 2021, 50 patients were prospectively enrolled in this study. Ruptured ATFL tissues were collected from 21 CLAI patients (group C) and 17 acute ankle fracture patients (group A). Apoptotic cells were counted using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Western blotting for caspases 3, 7, 8, and 9 and cytochrome c, was performed to explore intrinsic and extrinsic apoptotic pathways. Immunohistochemistry was used to detect caspases 3, 7, 8, and 9 and cytochrome c, in ligament vessel endothelial cells.

More apoptotic cells were observed in group C than group A in TUNEL assay. Western blotting revealed that the apoptotic activities of group C ligaments were significantly higher than those of group A (all p < 0.001). Immunohistochemistry revealed increased expression of caspases 3, 7, 8, and 9, and cytochrome c, in group C compared to group A.

The ATFL apoptotic activities of CLAI patients were significantly higher than those of acute ankle fracture patients, as revealed biochemically and histologically. Our data further validate current CLAI treatments from a molecular and cellular perspective. Efforts should be made to reverse or prevent ATFL apoptosis in CLAI patients.

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.

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.

After initial hesitance and failures, with growing knowledge about advanced products and their characteristics, increasingly more medtech and also pharma companies enter the advanced therapies market. However, due to the specifics of the biology and regulation of advanced therapy products, a lot of new know-how is necessary to be successful in this highly promising field.

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.

Majority of osteoporosis related fractures are treated surgically using metallic fixation devices. Anchorage of fixation devices is sometimes challenging due to poor osteoporotic bone quality that can lead to failure of the fracture fixation.

Using a rat osteoporosis model, we employed neutron tomography and histology to study the biological effects of implant augmentation using an isothermally setting calcium sulphate/hydroxyapatite (CaS/HA) biomaterial with synthetic HA particles as recruiting moiety for systemically administered bisphosphonates. Using an osteoporotic sawbones model, we then provide a standardized method for the delivery of the CaS/HA biomaterial at the bone-implant interface for improved mechanical anchorage of a lag-screw commonly used for hip fracture fixation. As a proof-of-concept, the method was then verified in donated femoral heads and in patients with osteoporosis undergoing hip fracture fixation.

We show that placing HA particles around a stainless-steel screw in-vivo, systemically administered bisphosphonates could be targeted towards the implant, yielding significantly higher peri-implant bone formation compared to un-augmented controls. In the sawbones model, CaS/HA based lag-screw augmentation led to significant increase (up to 4 times) in peak extraction force with CaS/HA performing at par with PMMA. Micro-CT imaging of the CaS/HA augmented lag-screws in cadaver femoral heads verified that the entire length of the lag-screw threads and the surrounding bone was covered with the CaS/HA material. X-ray images from fracture fixation surgery indicated that the CaS/HA material could be applied at the lag-screw-bone interface without exerting any additional pressure or risk of venous vascular leakage.: We present a new method for augmentation of lag-screws in fragile bone. It is envisaged that this methodcould potentially reduce the risk of fracture fixation failure especially when HA seeking “bone active” drugs are used systemically.

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.

Mechanical alignment (MA) in total knee arthroplasty (TKA), although considered the gold standard, reportedly has up to 25% of patients expressing post-operative dissatisfaction. Biomechanical outcomes following kinematic alignment (KA) in TKA, developed to restore native joint alignment, remain unclear. Without a clear consensus for the optimal alignment strategy during TKA, the purpose of this study was to conduct a paired biomechanical comparison of MA and KA in TKA by experimentally quantifying joint laxity and medial collateral ligament (MCL) strain.

14 bilateral native fresh-frozen cadaveric lower limbs underwent medially-stabilised TKA (GMK Sphere, Medacta, Switzerland) using computed CT-based subject-specific guides, with KA and MA performed on left and right legs, respectively. Each specimen was subjected to sensor-controlled mediolateral laxity tests. A handheld force sensor (Mark-10, USA) was used to generate an abduction-adduction moment of 10Nm at the knee at fixed flexion angles (0°, 30°, 60°, 90°). A digital image correlation system was used to compute the strain on the superficial medial collateral ligament. A six-camera optical motion capture system (Vicon MX+, UK) was used to acquire kinematics using a pre-defined CT-based anatomical coordinate system. A linear mixed model and Tukey's posthoc test were performed to compare native, KA and MA conditions (p<0.05).

Unlike MA, medial joint laxity in KA was similar to the native condition; however, no significant difference was found at any flexion angle (p>0.08). Likewise, KA was comparable with the native condition for lateral joint laxity, except at 30°, and no statistical difference was observed. Although joint laxity in MA seemed lower than the native condition, this difference was significant only for 30° flexion (p=0.01). Both KA and MA exhibited smaller MCL strain at 0° and 30°; however, all conditions were similar at 60° and 90°.

Medial and lateral joint laxity seemed to have been restored better following KA than MA; however, KA did not outperform MA in MCL strain, especially after mid-flexion. Although this study provides only preliminary indications regarding the optimal alignment strategy to restore native kinematics following TKA, further research in postoperative joint biomechanics for load bearing conditions is warranted.

Variations in component positioning of total hip replacements can lead to edge loading of the liner, and potentially affect device longevity. These effects are evaluated using ISO 14242:4 edge loading test results in a dynamic system. Mediolateral translation of one of the components during testing is caused by a compressed spring, and therefore the kinematics will depend on the spring stiffness and damping coefficient, and the mass of the translating component and fixture. This study aims to describe the sensitivity of the liner plastic strain to these variables, to better understand how tests using different simulator designs might produce different amounts of liner rim deformation.

A dynamic explicit deformable finite element model with 36mm Pinnacle metal-on-polyethylene bearing geometry (DePuy Synthes, Leeds, UK) was used with material properties for conventional UHMWPE. Setup was 65° clinical inclination, 4mm mismatch, 70N swing phase load, and 100N/mm spring. Fixture mass was varied from 0.5-5kg, spring damping coefficient was varied from 0-2Ns/mm. They were changed independently, and in combination.

Maximum separation values were relatively insensitive to changes in the mass, damping coefficient, or both. The sensitivity of peak plastic strain, to this range of inputs, was similar to changing the swing phase load from 70N to approximately 150N – 200N. Increasing the fixture mass and/or damping coefficient increased the peak plastic strain, with values from 0.15-0.19.

Liner plastic deformation was sensitive to the spring damping and fixture mass, which may explain some of the differences in fatigue and deformation results in UHMWPE liners tested on different machines or with modified fixtures. These values should be described when reporting the results of ISO14242:4 testing.

Acknowledgements

Funded by EPSRC grant EP/N02480X/1; CAD supplied by DePuy Synthes.

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.

Osteotomies in the musculoskeletal system are joint preserving procedures to correct the alignment of the patient. In the lower limb, most of the pre-operative planning is performed on full leg weightbearing radiographs. However, these images contain a 2-dimensional projection of a 3-dimensional deformity, lack a clear visualization of the joint surface and are prone to rotational errors during patient positioning. Weightbearing CT imaging has demonstrated to overcome these shortcomings during the first applications of this device at level of the foot and ankle. Recent advances allow to scan the entire lower limb and novel applications at the level of the knee and hip are on the rise. Here, we will demonstrated the current techniques and 3-dimensional measurements used in supra- and inframalleolar osteotomies around the ankle. Several of these techniques will be transposed to other parts in the lower limb to spark future studies in this field.

Metacarpal fractures represent up to 33% of all hand fractures; of which the majority can be treated non-operatively. Previous research has shown excellent putcomes with non-operative treatment yet surgical stabilisation is recommended to avoid malrotation and symptomatic shortening. It is unknown whether operative is superior to non-operative treatment in oblique or spiral metacarpal shaft fractures.

The aim of the study was to compare non-operative treatment of mobilisation with open surgical stabilisation.

42 adults (≥ 18 years) with a single displaced oblique or spiral metacarpal shaft fractures were randomly assigned in a 1:1 pattern to either non-operative treatment with free mobilisation or operative treatment with open reduction and fixation with lag screws in a prospective study. The primary outcome measure was grip-strength in the injured hand in comparison to the uninjured hand at 1-year follow-up. The Disabilities of the Arm, Shoulder and Hand Score, ranges of motion, metacarpal shortening, complications, time off work, patient satisfaction and costs were secondary outcomes.

All 42 patients attended final follow-up after 1 year. The mean grip strength in the non-operative group was 104% (range 73–250%) of the contralateral hand and 96% (range 58–121%) in the operatively treated patients. Mean metacarpal shortening was 5.0 (range 0–9) mm in the non-operative group and 0.6 (range 0–7) mm in the operative group. There were five minor complications and three revision operations, all in the operative group.

The costs for non-operative treatment were estimated at 1,347 USD compared to 3,834USD for operative treatment; sick leave was significantly longer in the operative group (35 days, range 0–147) than in the non-operative group (12 days, range 0–62) (p=0.008).

When treated with immediate free mobilization single, patients with displaced spiral or oblique metacarpal shaft fractures have outcomes that are comparable to those after operative treatment, despite some metacarpal shortening. Complication rates, costs and sick leave are higher with operative treatment. Early mobilisation of spiral or long oblique single metacarpal fractures is the preferred treatment.

Trial registration number: ClinicalTrials.gov NCT03067454

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.

Fractures and related complications are a common challenge in the field of skeletal tissue engineering. Vitamin D and calcium are the only broadly available medications for fracture healing, while zinc has been recognized as a nutritional supplement for healthy bones. Here, we aimed to use polaprezinc, an anti-ulcer drug and a chelate form of zinc and L-carnosine, as a supplement for fracture healing. Polaprezinc induced upregulation of osteogenesis-related genes and enhanced the osteogenic potential of human bone marrow-derived mesenchymal stem cells and osteoclast differentiation potential of mouse bone marrow-derived monocytes. In mouse experimental models with bone fractures, oral administration of polaprezinc accelerated fracture healing and maintained a high number of both osteoblasts and osteoclasts in the fracture areas. Collectively, polaprezinc promotes the fracture healing process efficiently by enhancing the activity of both osteoblasts and osteoclasts. Therefore, we suggest that drug repositioning of polaprezinc would be helpful for patients with fractures.

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.

Biphasic calcium phosphate (BCP) with a characteristic needle-shaped submicron surface topography (MagnetOs) has attracted much attention due to its unique bone-forming ability which is essential for repairing critical-size bone defects such as those found in the posterolateral spine. Previous in vitro and ex-vivo data performed by van Dijk LA and Yuan H demonstrated that these specific surface characteristics drive a favorable response from the innate immune system.

This study aimed to evaluate and compare the in vivo performance of three commercially-available synthetic bone grafts, (1) i-FACTOR Putty^®, (2) OssDsign^® Catalyst Putty and (3) FIBERGRAFT^® BG Matrix, with that of a novel synthetic bone graft in a clinically-relevant instrumented sheep posterolateral lumbar spine fusion (PLF) model. The novel synthetic bone graft comprised of BCP granules with a needle-shaped submicron surface topography (MagnetOs) embedded in a highly porous and fibrillar collagen matrix (MagnetOs Flex Matrix).

Four synthetic bone grafts were implanted as standalone in an instrumented sheep PLF model for 12 weeks (n=3 bilateral levels per group; levels L2/3 & L4/5), after which spinal fusion was determined by manual palpation, radiograph and µCT imaging (based on the Lenke scale), range-of-motion mechanical testing, and histological and histomorphological evaluation.

Radiographic fusion assessment determined bilateral robust bone bridging (Lenke scale A) in 3/3 levels for MagnetOs Flex Matrix compared to 1/3 for all other groups. For µCT, bilateral fusion (Lenke scale A) was found in 2/3 levels for MagnetOs Flex Matrix, compared to 0/3 for i-FACTOR Putty^®, 1/3 for OssDsign^® Catalyst Putty and 0/3 for FIBERGRAFT^® BG Matrix. Fusion assessment for MagnetOs Flex Matrix was further substantiated by histology which revealed significant graft resorption complemented by abundant bone tissue and continuous bony bridging between vertebral transverse processes resulting in bilateral spinal fusion in 3/3 implants.

These results show that MagnetOs Flex Matrix achieved better fusion rates compared to three commercially-available synthetic bone grafts when used as a standalone in a clinically-relevant instrumented sheep PLF model.

Vacuum orthoses are being applied in the care of patients with foot and lower leg conditions, as ankle fractures or sprains. The lower leg is protected and immobilized, which increases mobility. Due to the design, the orthoses lead to a difference in leg length, i.e. the side with the orthosis becomes longer, which changes the gait kinematics. To prevent or mitigate the unfavourable effects of altered gait kinematics, leg length-evening devices (shoe lifts) are offered that are worn under the shoe on the healthy side. Our aim was to evaluate the effect of such a device on the normality of gait kinematics.

Gait analysis was conducted with 63 adult, healthy volunteers having signed an informed consent form that were asked to walk on a treadmill at a speed of 4.5km/h in three different conditions:

Data was sampled using the gait analysis system MCU 200 (LaiTronic GmbH, Austria). The positions of the joint markers were exported from the software and evaluated for the joint angles during the gait cycle using custom software (implemented in DIAdem 2017, National Instruments).

A normality score using a modification of the Gait Profile Score (GPS) was calculated in every 1%-interval of the gait cycle and evaluated with a Wilcoxon signed rank test.

The GPS value was reduced by 0.33° (0.66°) (median and IQR) while wearing the shoe lift. The effect was statistically significant, and very large (W = 1535.00, p < .001; r (rank biserial) = 0.52, 95% CI [0.29, 0.70]).

The significant reduction of the GPS value indicates a more normal gait kinematics while using the leg length-evening device on the contralateral shoe. This rather simple and inexpensive device thus might improve patient comfort and balance while using the vacuum orthoses.

The use of intraoperative navigation and robotic surgery for minimally invasive lumbar fusion has been increasing over the past decade. The aim of this study is to evaluate postoperative clinical outcomes, intraoperative parameters, and accuracy of pedicle screw insertion guided by intraoperative navigation in patients undergoing lumbar interbody fusion for spondylolisthesis. Patients who underwent posterior lumbar fusion interbody using intraoperative 3D navigation since December 2021 were included. Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Short Form Health Survey-36 (SF-36) were assessed preoperatively and postoperatively at 1, 3, and 6 months. Screw placement accuracy, measured by Gertzbein and Robbins classification, and facet joint infringement, measured by Yson classification, were assessed by intraoperative Cone Beam CT scans performed at the end of instrumentation. Finally, operation time, intraoperative blood loss, hospital stay, and screw insertion time were evaluated. This study involved 50 patients with a mean age of 63.7 years. VAS decreased from 65.8±23 to 20±22 (p<.01). ODI decreased from 35.4%±15 to 11.8%±14 (p<.01). An increase of SF-36 from 51.5±14 to 76±13 (p<.01) was demonstrated. The accuracy of “perfect” and “clinically acceptable” pedicle screw fixation was 89.5% and 98.4%, respectively. Regarding facet violation, 96.8% of the screws were at grade 0. Finally, the average screw insertion time was 4.3±2 min, hospital stay was 4.2±0.8 days, operation time was 205±53 min, and blood loss was 169±107 ml. Finally, a statistically significant correlation of operation time with hospital stay, blood loss and placement time per screw was found. We demonstrated excellent results for accuracy of pedicle screw fixation and violation of facet joints. VAS, ODI and SF-36 showed statistically significant improvements from the control at one month after surgery.

Navigation with intraoperative 3D images represents an effective system to improve operative performance in the surgical treatment of spondylolisthesis.

Acute syndesmotic ankle injuries continue to impose a diagnostic dilemma and it remains unclear whether weighbearing or external rotation should be exerted rotation during the imaging process. Therefore, we aimed to implement both axial load (weightbearing) and external rotation in the assessment of a clinical cohort of patients with syndesmotic ankle injuries syndesmotic using weightbearing CT imaging. In this retrospective comparative cohort study, patients with an acute syndesmotic ankle injury were analyzed using a WBCT (N= 20; Mean age= 31,64 years; SD= 14,07. Inclusion criteria were an MRI confirmed syndesmotic ankle injury imaged by a bilateral WBCT of the ankle during weightbearing and combined weightbearing-external rotation. Exclusion criteria consisted of fracture associated syndesmotic ankle injuries. Three-dimensional (3D) models were generated from the CT slices. Tibiofibular displacement and Talar Rotation was quantified using automated3D measurements (Anterior TibioFibular Distance (ATFD), Alpha Angle, Posterior TibioFibular Distance (PTFD) and Talar Rotation (TR) Angle) in comparison to a cohort of non-injured ankles.

Treatment of bone infection often includes a burdensome two-stage revision. After debridement, contaminated implants are removed and replaced with a non-absorbable cement spacer loaded with antibiotics. Weeks later, the spacer is exchanged with a bone graft aiding bone healing. However, even with this two-stage approach infection persists. In this study, we investigated whether a novel 3D-printed, antibiotic-loaded, osteoinductive calcium phosphate scaffold (CPS) is effective in single-stage revision of an infected non-union with segmental bone loss in rabbits.

A 5 mm defect was created in the radius of female New Zealand White rabbits. The bone fragment was replaced, stabilized with cerclage wire and inoculated with Staphylococcus aureus (MSSA). After 4 weeks, the infected bone fragment was removed, the site debrided and a spacer implanted. Depending on group allocation, rabbits received: 1) PMMA spacer with gentamycin; 2) CPS loaded with rifampin and vancomycin and 3) Non-loaded CPS. These groups received systemic cefazolin for 4 weeks after revision. Group 4 received a loaded CPS without any adjunctive systemic therapy (n=12 group1-3, n=11 group 4). All animals were euthanized 8 weeks after revision and assessed by quantitative bacteriology or histology. Covariance analysis (ANCOVA) and multiple regression were performed.

All animals were culture positive at revision surgery. Half of the animals in all groups had eliminated the infection by end of study. In a historical control group with empty defect and no systemic antibiotic treatment, all animals were infected at euthanasia. There was no significant difference in CFU counts between groups at euthanasia.

Our results show that treating an osteomyelitis with segmental bone loss either with CPS or PMMA has a similar cure rate of infection. However, by not requiring a second surgery, the use of CPS may offer advantages over non-resorbable equivalents such as PMMA.

Rotator cuff tears are common, with failure rates of up to 94% for large and massive tears¹. For such tears, reattachment of the musculotendinous unit back to bone is problematic, and any possible tendon-bone repair heals through scar tissue rather than the specially adapted native enthesis. We aim to develop and characterise a novel soft-hard tissue connector device, specific to repairing/bridging the tendon-bone injury in significant rotator cuff tears, employing decellularised animal bone partially demineralised at one end for soft tissue continuation.

Optimisation samples of 15×10×5mm³, trialled as separate cancellous and cortical bone samples, were cut from porcine femoral condyles and shafts, respectively. Samples underwent 1-week progressive stepwise decellularisation and a partial demineralisation process of half wax embedding and acid bathing. Characterisations were performed histologically for the presence/absence of cellular staining in both peripheral and central tissue areas (n=3 for each cortical/cancellous, test/PBS control and peripheral/central group), and with BioDent reference point indentation (RPI) for pre- and post-processing mechanical properties.

Histology revealed absent cellular staining in peripheral and central cancellous samples, whilst reduced in cortical samples compared to controls. Cancellous samples decreased in wet mass after decellularisation by 45.3% (p<0.001). RPI measurements associated with toughness (total indentation depth, indentation depth increase) and elasticity (1st cycle unloading slope) showed no consistent changes after decellularisation. X-rays confirmed half wax embedding provided predictable control of the mineralised-demineralised interface position.

Initial optimisation trials show proof-of-concept of a soft-hard hybrid scaffold as an immune compatible xenograft for irreparable rotator cuff tears. Decellularisation did not appreciably affect mechanical properties, and further biological, structural and chemical characterisations are underway to assess validity before in vivo animal trials and potential clinical translation.

Freehand distal interlocking of intramedullary nails is technical demanding and prone to handling issues. It requires the surgeon to precisely place a screw through the nail under x-ray. If not performed accurately it can be a time consuming and radiation expensive procedure. The aims of this study were to assess construct and face validity of a new training device for distal interlocking of intramedullary nails.

53 participants (29 novices and 24 experts) were included. Construct validity was evaluated by comparing simulator metrics (number of x-rays, nail hole roundness, drill tip position and accuracy of the drilled hole) between experts and novices. Face validity was evaluated by means of a questionnaire concerning training potential and quality of simulated reality using a 7-point Likert scale (range 1-7).

Mean realism of the training device was rated 6.3 (range 4-7) and mean training potential as well as need for distal interlocking training was rated 6.5 (range 5-7) with no significant differences between experts and novices, p≥0.236. All participants stated that the simulator is useful for procedural training of distal nail interlocking, 96% would like to have it at their institution and 98% would recommend it to their colleagues. Total number of x-rays were significantly higher for novices (20.9±6.4 vs. 15.5±5.3), p=0.003. Successful task completion (hit the virtual nail hole with the drill) was significantly higher in experts (p=0.04; novices hit: n=12; 44,4%; experts hit: n=19; 83%).

The evaluated training device for distal interlocking of intramedullary nails yielded high scores in terms of training capability and realism. Furthermore, construct validity was established as it reliably discriminates between experts and novices. Participants see a high further training potential as the system may be easily adapted to other surgical task requiring screw or pin position with the help of x-rays.

Dupuytren's disease (DD) is a fibroproliferative soft tissue disease affecting the palmar fascia of the hand causing permanent and irreversible flexion contracture. Aberrant fibrosis is likely to manifest through a combination of extrinsic, intrinsic, and environmental factors, including genetics and epigenetics. However, the role of epigenetics in soft tissue fibrosis in diseases such as DD is not well established. Therefore, we conducted a comprehensive multi-omic study investigating the epigenetic profiles that influence gene expression in DD pathology. Using control (patients undergoing carpal tunnel release) and diseased fibroblasts (patients undergoing Dupuytren's fasciectomy), we conducted ATAC-seq to assess differential chromatin accessibility between control and diseased fibroblasts. Additionally, ChIP-seq mapped common histone modifications (histone H4; H3K4me3, H3K9me3, H3K27me3, H4K16Ac, H4K20Me3) associated with fibrosis. Furthermore, we extracted RNA from control and DD tissue and performed bulk RNA-seq.

ATAC-seq analysis identified 2470 accessible genomic loci significantly more accessible in diseased fibroblasts compared to control. Comparison between diseased and control cells identified numerous significantly different peaks in histone modifications (H4K20me3, H3K27me3, H3K9me3) associated with gene repression in control cells but not in diseased cells. Pathway analysis demonstrated a substantial overlap in genes being de-repressed across these histone modifications (Figure 1). Both, ATAC-seq and ChIP-seq analysis indicated pathways such as cell adhesion, differentiation, and extracellular matrix organisation were dysregulated as a result of epigenetic changes. Moreover, de novo motif enrichment analysis identified transcription factors that possibly contributed to the differential gene expression between control and diseased tissue, including HIC1, NFATC1 and TEAD2. RNA-seq analysis found that these transcription factors were upregulated in DD tissue compared to control tissue.

The current epigenetic study provides insights into the aberrant fibrotic processes associated with soft tissue diseases such as DD and indicates that epigenetic-targeted therapies may be an interesting viable treatment option in future.

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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.

There is a lack of carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotic for Staphylococcus aureus deep bone infections (DBIs). RIF is also associated with systemic side effects, and known for causing rapid development of antibiotic resistance when given as monotherapy. We evaluated a clinically usedbi-phasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). It was hypothesized that this combined approach could provide improved biofilm eradication and prevent the development of RIF resistance.

Methods: 1) Biofilm eradication: Using a modified crystal violet staining biofilm quantification method, the antibiotics released at different time points (Day 1, 3, 7, 14, 21, 28 and 35) from the hemispherical pellets of CaS/HA(500 mg)-VAN (24.57 mg) / GEN (10.35 mg) composites with or without RIF (8.11 mg) were tested for their ability to disrupt the preformed 48-h old biofilms of S. aureus ATCC 25923, and S. aureus clinical strain P-3 in 96-well microtitre plate. For each tested group of antibiotic fractions, five separate wells were used (n=5). 2) Testing for resistance development: Similar to the method mentioned above the 48-h biofilm embeded bacteria exposed to antibiotic fractions from different time points continuously for 7 days. The biofilms remained were then tested for RIF resistant strains of bacteria.

Overall, there was clear antibiofilm biofilm activity observed with CaS/HA-VAN/GEN+RIF combinations compared with CaS/HA-VAN/GEN alone. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with combinations of CaS/HA-VAN/GEN+RIF

Enhanced antibiofilm effects without development of RIF resistance indicates that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for additional local delivery in clinically demanding DBIs.

Acknowledgement: We deeply acknowledge the Royal Fysiographic Society of Lund, Landshövding Per Westlings Minnesfond and the Stina and Gunnar Wiberg fond for financial support.

Total knee replacement (TKR) design aims to restore normal kinematics with emphasis on flexion range. The survivorship of a TKR is dependent on the kinematics in six-degrees-of-freedom (6-DoF). Stepping up, such as stair ascent is a kinematically demanding activity after TKR. The debate about design choice has not yet been informed by 6-DoF in vivo kinematics. This prospective randomised controlled trial (RCT) compared kneeling kinematics in three TKR designs.

68 participants were randomised to receive either cruciate retaining (CR-FB), rotating platform (CR-RP) or posterior stabilised (PS-FB) prostheses. Image quality was sufficient for 49 of these patients to be included in the final analysis following a minimum 1-year follow-up. Patients completed a step-up task while being imaged using single-plane fluoroscopy. Femoral and tibial computer-aided design (CAD) models for each of the TKR designs were registered to the fluoroscopic images using bespoke software OrthoVis to generate six-degree-of-freedom kinematics. Differences in kinematics between designs were compared as a function of flexion.

There were no differences in terminal extension between the groups. The CR-FB was further posterior and the CR-RP was more externally rotated at terminal extension compared to the other designs. Furthermore, the CR-FB designs was more posteriorly positioned at each flexion angle compared to both other designs. Additionally, the CR-RP design had more external femoral rotation throughout flexion when compared with both fixed bearing designs. However, there were no differences in total rotation for either step-up or down. Visually, it appears there was substantial variability between participants in each group, indicating unique patient-specific movement patterns.

While use of a specific implant design does influence some kinematic parameters, the overall patterns are similar. Furthermore, there is high variability indicating patient-specific kinematic patterns. At a group level, none of these designs appear to provide markedly different step-up kinematic patterns. This is important for patient expectations following surgery. Future work should aim to better understand the unique patient variability.

Tryfonidou leads the Horizon 2020 consortium (iPSpine; 2019–2023) bringing a transdisciplinary team of 21 partners together to address the challenges and bottlenecks of iPS-based advanced therapies towards their transition to the clinic. Here, chronic back pain due to intervertebral disc degeneration is employed as a show case. The project develops the iPS-technology and designed smart biomaterials to carry, protect and instruct the iPS cells within the degenerate disc environment. This work will be presented including ongoing activities focus on translating the developed methodology and tools towards clinically relevant animal models.

The consortium optimized the protocol for the differentiated iPS-notochordal-like cells (iPS-NLCs) and shortlisted two biomaterials shortlisted based on their physicochemical, cytotoxicity, biomechanical and biocompatibility testing. Both were shown to be safe and have been tested with the progenitors of iPS-NLCs. An advanced platform (e.g., the dynamic loading bioreactor for disc tissue) was used to evaluate their performance: the biomaterials supported the iPS-NLC progenitors after injection into the degenerate disc and seem to also support their maturation towards NLCs. Furthermore, we confirmed the capacity of these cells to survive inside degenerated discs at 30 days upon injection in sheep, whereafter we continued with their evaluation at 3 months post-injection. We achieved full evaluation of the sheep spines, including biomechanical analysis using the portable spine biomechanics tester prior analysis at the macro- and microscopic, and biochemical level.

Ligament integrity is directly associated with ankle stability. Nearly 40% of ankle sprains result in chronic ankle instability, affecting biomechanics and potentially causing osteoarthritis. Ligament replacement could restore stability and avoid this degenerative pathway, but a greater understanding of ankle ligament behaviour is required. Additionally, autograft or allograft use is limited by donor-site morbidity and inflammatory responses respectively. Decellularised porcine grafts could address this, by removing cellular material to prevent acute immune responses, while preserving mechanical properties.

This project will characterise commonly injured ankle ligaments and damage mechanisms, identify ligament reconstruction requirements, and investigate the potential of decellularised porcine grafts as a replacement material.

Several porcine tendons were evaluated to identify suitable candidates for decellularisation. The viscoelastic properties of native tissues were assessed using dynamic mechanical analysis (DMA), followed by ramp to ‘sub-rupture’ at 1% strain/s, and further DMA. Multiple samples (n=5) were taken along the graft to assess variation along the tendon.

When identifying suitable porcine tendons, a lack of literature on human ankle ligaments was identified. Inconsistencies in measurement methods and properties reported makes comparison between studies difficult.

Preliminary testing on porcine tendons suggested there is little variation in viscoelastic properties along the length of tendon. Testing also suggested strain rates of 1%/s sub-rupture was not large enough to affect viscoelastic properties (no changes in storage or loss moduli or tanẟ). Further testing is underway to improve upon low initial sample numbers and confirm these results, with varying strain rates to identify suitable sub-rupture sprain conditions.

This work highlights need for new data on human ankle ligaments to address knowledge gaps and identify suitable replacement materials. Future work will generate this data and decellularise porcine tendons of similar dimensions. Collagen damage will be investigated using histology and lightsheet microscopy, and viscoelastic changes through DMA.

Cam-type femoroacetabular impingement is caused by bone excess on the femoral neck abutting the acetabular rim. This can cause cartilage and labral damage due to increased contact pressure as the cam moves into the acetabulum. However, the damage mechanism and the influence of individual mechanical factors (such as sliding distance) are poorly understood. The aim of this study was to identify the cam sliding distance during impingement for different activities in the hip joint.

Motion data for 12 different motion activities from 18 subjects, were applied to a hip shape model (selected as most likely to cause damage, anteriorly positioned with a maximum alpha angle of 80°). The model comprised of a pointwise representation of the acetabular rim and points on the femoral head and neck where the shape deviated from a sphere (software:Matlab).

The movement of each femoral point was tracked in 3D while an activity motion was applied, and impingement recorded when overlap between a cam point and the acetabular rim occurred. Sliding distance was recorded during impingement for each relevant femoral point.

Angular sliding distances varied for different activities. The highest mean (±SD) sliding distance was for leg-crossing (42.62±17.96mm) and lowest the trailing hip in golf swing (2.17±1.11mm). The high standard deviation in the leg crossing sliding distances, indicates subjects may perform this activity in a different manner.

This study quantified sliding distance during cam impingement for different activities. This is an important parameter for determining how much the hip moves during activities that may cause damage and will provide information for future experimental studies.

Prosthetic joint infection (PJI) is an important cause of arthroplasty failure. There is no method to disclose the presence or map the distribution of the in vivo biofilm on infected arthroplasty despite the recognition that such a tool would aid intraoperative decision making and improve novel implant design. The aim of this study was to test the efficacy of four dyes to disclose bacterial biofilm in an in vitro setting.

Four dyes with known affinity to bacterial biofilm were assessed to determine their efficacy to disclose biofilms in an in vitro model of PJI. Three dyes (Methylene Blue, Indocyanine Green and Rose Bengal) have established clinical utility and the other, Thioflavin T, is known to fluoresce in the presence of amyloid a known biofilm constituent. The efficacy of the dyes to discriminate between biofilms of different mass and vitality (high, low or the non-inoculated control) was determined after three minutes exposure of the biofilm to the dyes by calculating the amount of dye bound to the biofilm via sonication and spectrophotometry, quantification of the dye through standardised photographic imaging of the stained biofilm and the calculation of inter-observer agreement. Each experiment was performed in triplicate for each dye and repeated three times.

For each of the disclosure dyes assessed there was significant difference demonstrated between the amount of dye bound to the high and low mass biofilms (p<0.05) as well as in the amount of dye quantified in photographic and fluorescent image assessment between biofilms of differing mass (p<0.01). There was excellent agreement between three observers, for each disclosure dye, in determining the biofilm mass of each stained disc (Kappa>0.91).

This study demonstrates the efficacy of biofilm disclosure dyes in an in vitro PJI model which could one day be used to disclose and map the clinical biofilm in vivo.

Low back pain is strongly associated with degeneration of the intervertebral disc (IVD). During degeneration, altered matrix synthesis and increased matrix degradation, together with accompanied cell loss is seen particularly in the nucleus pulposus (NP). It has been proposed that notochordal (NC) cells, embryonic precursors for the cells within the NP, could be utilized for mediating IVD regeneration. However, injectable biomaterials are likely to be required to support their phenotype and viability within the degenerate IVD. Therefore, viability and phenotype of NC cells were analysed and compared within biomaterial carriers subjected to physiological oxygen conditions over a four-week period were investigated.

Porcine NC cells were incorporated into three injectable hydrogels: NPgel (a L-pNIPAM-co-DMAc hydrogel), NPgel with decellularized NC-matrix powder (dNCM) and Albugel (an albumin/ hyaluronan hydrogel). The NCs and biomaterials constructs were cultured for up to four weeks under 5% oxygen (n=3 biological repeats). Histological, immunohistochemical and glycosaminoglycans (GAG) analysis were performed to investigate NC viability, phenotype and extracellular matrix synthesis and deposition.

Histological analysis revealed that NCs survive in the biomaterials after four weeks and maintained cell clustering in NPgel, Albugel and dNCM/NPgel with maintenance of morphology and low caspase 3 staining. NPgel and Albugel maintained NC cell markers (brachyury and cytokeratin 8/18/19) and extracellular matrix (collagen type II and aggrecan). Whilst Brachyury and Cytokeratin were decreased in dNCM/NPgel biomaterials, Aggrecan and Collagen type II was seen in acellular and NC containing dNCM/NPgel materials. NC containing constructs excreted more GAGs over the four weeks than the acellular controls.

NC cells maintain their phenotype and characteristic features in vitro when encapsulated into biomaterials. NC cells and biomaterial construct could potentially become a therapy to treat and regenerate the IVD.

Tissue repair is believed to rely on tissue-resident progenitor cell populations proliferating, migrating, and undergoing differentiation at the site of injury. During these processes, the crosstalk between mesenchymal stromal/stem cells (MSCs) and macrophages has been shown to play a pivotal role. However, the influence of extracellular matrix (ECM) remodelling in this crosstalk, remains elusive.

Human MSCs cultured on tissue culture plastic (TCP) and encased within fibrin in vitro were treated with/without TNFα and IFNγ. Human monocytes were cocultured with untreated/pretreated MSCs on TCP or within fibrin. After seven days, the conditioned media (CM) were collected. Human chondrocytes were exposed to CM in a migration assay. The impact of TGFβ was assessed by adding an inhibitor (TGFβRi). Cell activity was assessed using RT-qPCR and XL-protein-profiler-array.

Previously, we demonstrated that culturing human MSCs within 3D-environments significantly enhances their immunoregulatory activity in response to pro-inflammatory stimuli. In this study, monocytes were co-cultured with MSCs within fibrin, acquiring a distinct M2-like repair macrophage phenotype in contrast to TCP co-cultures. MSC/macrophage CM characterization using a protein array demonstrated differences in release of several factors, including chemokines, growth factors and ECM components. Chondrocyte migration was significantly reduced in CM from untreated MSC/monocytes co-cultures in fibrin compared to CM of untreated MSCs/monocytes on TCP. This impact on migration was not seen with chondrocytes cultured in CM of monocytes co-cultured with pretreated MSCs in fibrin. The CM of monocytes co-cultured with pretreated MSCs in fibrin up-regulates COL2A1 and SOX9 compared to TCP. Chondrogenesis and migration were TGFβ dependent.

MSC/macrophage crosstalk and responsiveness to cytokines are influenced by the ECM environment, which subsequently impacts tissue-resident cell migration and chondrogenesis. The direct effects of ECM on MSC/macrophage secretory phenotype is complemented by the dynamic ECM binding and release of growth factors such as TGFβ.

Determine the infection risk of nonoperative versus operative repair of extraperitoneal bladder ruptures in patients with pelvic ring injuries. Pelvic ring injuries with extraperitoneal bladder ruptures were identified from a prospective trauma registry at two level 1 trauma centers from 2014 to 2020. Patients, injuries, treatments, and complications were reviewed. Using Fisher's exact test with significance at P value < 0.05, associations between injury treatment and outcomes were determined.

Of the 1127 patients with pelvic ring injuries, 68 (6%) had a concomitant extraperitoneal bladder rupture.

All patients received IV antibiotics for an average of 2.5 days. A suprapubic catheter was placed in 4 patients. Bladder repairs were performed in 55 (81%) patients, 28 of those simultaneous with ORIF anterior pelvic ring. The other 27 bladder repair patients underwent initial ex-lap with bladder repair and on average had pelvic fixation 2.2 days later. Nonoperative management of bladder rupture with prolonged Foley catheterization was used in 13 patients. Improved fracture reduction was noted in the ORIF cohort compared to the closed reduction external fixation cohort (P = 0.04).

There were 5 (7%) deep infections. Deep infection was associated with nonoperative management of bladder rupture (P = 0.003) and use of a suprapubic catheter (P = 0.02). Not repairing the bladder increased odds of infection 17-fold compared to repair (OR 16.9, 95% CI 1.75 – 164, P = 0.01).

Operative repair of extraperitoneal bladder ruptures substantially decreases risk of infection in patients with pelvic ring injuries. ORIF of anterior pelvic ring does not increase risk of infection and results in better reductions compared to closed reduction. Suprapubic catheters should be avoided if possible due to increased infection risk later. Treatment algorithms for pelvic ring injuries with extraperitoneal bladder ruptures should recommend early bladder repair and emphasize anterior pelvic ORIF.

Since the emergence of the COVID-19 pandemic, the NHS has been under unprecedentedpressure. Elective surgery had ceased, and trauma surgery has decreased dramatically. Surgical training is multi-faceted and requires a specialist trainee to have a timetable which includes regular elective non-emergency operating, trauma operating and training in outpatient clinics. Consequently, training in theatre and the achievement of operative numbers and index procedures had not been possible for Trauma and Orthopaedic (T&O) specialist trainees.

The Joint Committee on Surgical Training (JCST) has clear training index requirements for all T&O specialist trainees. In this study, we surveyed specialist trainees in the North West London deanery against the annual requirements set by the JCST guidelines. In addition, we retrospectively assessed the total number of trauma referrals and operations scheduled in our unit during the COVID-19 outbreak compared to that one year previously. The aim of this study is to objectively assess the effect the pandemic has on T&O specialist training.

A total of 24 responses were collected from specialist trainees. The results of the survey showed 87% of trainees believed that their training had been affected. 75% of trainees felt they were not on track to meet operative numbers for the year, and 71% felt index number achievement had been affected. Trauma case numbers dropped by 20% compared to that one year previously.

We recommend timely, planned and conscientious remediation for specialist trainees’ educational requirements. Specialist trainees must take responsibility for their training and use of additional educational opportunities. Clinical supervisors and training programme directors must provide additional support and guidance to achieve ARCP outcomes however in some scenarios extension of training may be necessary.