Autologous cancellous bone graft is the gold standard in large bone defect repair. However, studies using autologous bone grafting in rats are rare and donor sites as well as harvesting techniques vary. The aim of this study was to determine the feasibility of autologous cancellous bone graft harvest from 5 different anatomical sites in rats and compare their suitability as donor sites for autologous bone graft.

13 freshly euthanised rats were used to describe the surgical approaches for autologous bone graft harvest from the humerus, iliac crest, femur, tibia and tail vertebrae (n=4), determine the cancellous bone volume and microstructure of those five donor sites using µCT (n=5), and compare their cancellous bone collected qualitatively by looking at cell outgrowth and osteogenic differentiation using an ALP assay and Alizarin Red S staining (n=4).

It was feasible to harvest cancellous bone graft from all 5 anatomical sites with the humerus and tail being more surgically challenging. The microstructural analysis showed a significantly lower bone volume fraction, bone mineral density, and trabecular thickness of the humerus and iliac crest compared to the femur, tibia, and tail vertebrae. The harvested volume did not differ between the donor sites. All donor sites apart from the femur yielded primary osteogenic cells confirmed by the presence of ALP and Alizarin Red S stain. Bone samples from the iliac crest showed the most consistent outgrowth of osteoprogenitor cells.

The tibia and iliac crest may be the most favourable donor sites considering the surgical approach. However, due to the differences in microstructure of the cancellous bone and the consistency of outgrowth of osteoprogenitor cells, the donor sites may have different healing properties, that need further investigation in an in vivo study.

Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis, which occurs secondary to traumatic joint injury which is known to cause pathological changes to the osteochondral unit. Articular cartilage degradation is a primary hallmark of OA, and is normally associated with end-stage disease. However, subchondral bone marrow lesions are associated with joint injury, and may represent localized bone microdamage. Changes in the osteochondral unit have been traditionally studied using explant models, of which the femoral-head model is the most common. However, the bone damage caused during harvest can confound studies of microdamage. Thus, we used a novel patellar explant model to study osteochondral tissue dynamics and mechanistic changes in bone-cartilage crosstalk.

Firstly, we characterized explants by comparing patella with femoral head models. Then, the patellar explants (n=269) were subjected to either mechanical or inflammatory stimulus. For mechanical stimulus 10% strain was applied at 0.5 and 1 Hz for 10 cycles. We also studied the responses of osteochondral tissues to 10ng/ml of TNF-α or IL-1β for 24hrs.

In general the findings showed that patellar explant viability compared extremely well to the femoral head explant. Following IL-1β or TNF-α treatment, MMP13, significantly increased three days post exposure, furthermore we observed a decrease in sulfate glycoaminoglycan (sGAG) content. Bone morphometric analysis showed no significant changes. Contrastingly, mechanical stimulation resulted in a significant decrease sGAG particularly at 0.5Hz, where an increase in MMP13 release 24hrs post stimulation and an upregulation of bone and cartilage matrix degradation markers was observed. Furthermore, mechanical stimulus caused increases in TNF-α, MMP-8, VEGF expression.

In summary, this study demonstrates that our novel patella explant model is an excellent system for studying bone-cartilage crosstalk, which responds well to both mechanical and inflammatory stimulus and is thus of great utility in the study of PTOA.

The use of mesenchymal stromal cells (MSCs) in regenerative medicine and tissue engineering is well established, given their properties of self-renewal and differentiation. However, several studies have shown that these properties diminish with age, and understanding the pathways involved are important to provide regenerative therapies in an ageing population.

In this PRISMA systematic review, we investigated the effects of chronological donor ageing on the senescence of MSCs. We identified 3023 studies after searching four databases including PubMed, Web of Science, Cochrane, and Medline. Nine studies met the inclusion and exclusion criteria and were included in the final analyses.

These studies showed an increase in the expression of p21, p53, p16, ROS, and NF- B with chronological age. This implies an activated DNA damage response (DDR), as well as increased levels of stress and inflammation in the MSCs of older donors. Additionally, highlighting the effects of an activated DDR in cells from older donors, a decrease in the expression of proliferative markers including Ki67, MAPK pathway elements, and Wnt/ -catenin pathway elements was observed. Furthermore, we found an increase in the levels of SA- -galactosidase, a specific marker of cellular senescence.

Together, these findings support an association between chronological age and MSC senescence. The precise threshold for chronological age where the reported changes become significant is yet to be defined and should form the basis for further scientific investigations. The outcomes of this review should direct further investigations into reversing the biological effects of chronological age on the MSC senescence phenotype.

Unicompartmental knee arthroplasty (UKA) is associated with a higher risk of revision compared with total knee arthroplasty (TKA). The outcomes of knee arthroplasty are typically presented as implant survival or incidence of revision after a set number of years, which can be difficult for patients and clinicians to conceptualise. We aimed to calculate the ‘lifetime risk’ of revision for UKA as a more relatable estimate of risk projection over a patient's remaining lifetime, and make comparisons to TKA. All primary UKAS performed from 1999 to 2019 (n=13,481) captured by the New Zealand Joint Registry (NZJR) were included. The lifetime risk of revision was calculated and stratified by age, gender and American Society of Anesthesiologists (ASA) status. The lifetime risk of revision for UKA was highest in the youngest patients (46-50 years; 40.4%) and lowest in the oldest patients (86-90 years; 3.7%). Lifetime risk of revision was higher for females (range 4.3%-43.4% cf. males 2.9%-37.4%) and patients with higher ASA status (ASA 3-4 range 8.8%-41.2% cf. ASA 1 1.8%-29.8%), regardless of age. The lifetime risk of UKA was two-fold higher than TKA (ranging from 3.7%-40.4% UKA, 1.6%-22.4% TKA) across all age groups. Increased risk of revision in the younger patients was associated with aseptic loosening in both males and females, and pain in females. Periprosthetic joint infections (PJI) accounted for 4% of all UKA revisions, in contrast to 27% for TKA; risk of PJI was higher for males than females for both procedures. The lifetime risk of revision is a more meaningful measure of arthroplasty outcomes and can aid with patient counselling prior to UKA. Findings from this study show the increased lifetime risk of UKA revision for younger patients, females and those with higher ASA status.

Anterior vertebral body tethering (AVBT) is a growth modulating procedure used to manage idiopathic scoliosis by applying a flexible tether to the convex surface of the spine in skeletally immature patients. The purpose of this study is to determine the preliminary clinical outcomes for an adolescent patient cohort.

18 patients with scoliosis were selected using a narrow selection criteria to undergo AVBT. Of this cohort, 11 had reached a minimum follow up of 2 years, 4 had reached 18 months, and 3 had reached 6 months. These patients all demonstrated a primary thoracic deformity that was too severe for bracing, were skeletally immature, and were analysed in this preliminary study of coronal plane deformity correction.

Using open-source image analysis software (ImageJ, NIH) PA radiographs taken pre-operatively and at regular follow-up visits post-operatively were used to measure the coronal plane deformity of the major and compensatory curves.

Pre-operatively, the mean age was 12.0 years (S.D. 10.7 – 13.3), mean Sanders score 2.6 (S.D. 1.8-3.4), all Risser 0 and pre-menarchal, with mean main thoracic Cobb angle of 52° (S.D. 44.2-59.8°). Post-operatively the mean angle decreased to 26.4° (S.D. 18.4-32°) at 1 week, 30.4° (S.D. 21.3-39.6°) at 2 months, 25.7° (S.D. 18.7-32.8°) at 6 months, 27.9° (S.D. 16.2-39.6°) at 12 months, and 36.8° (S.D. 22.6– 51.0°) at 18 months and 38.2° (S.D. 27.6-48.7°) at 2 years. The change in curve at 2 years post-operative was statistically significant (P=0.004).

There were 4 tether breakages identified that did not require return to theatre as yet, one patient underwent a posterior spinal instrumented fusion due to curve progression.

AVBT is a promising new growth modulation technique for skeletally immature patients with progressive idiopathic scoliosis. This study has demonstrated a reduction in scoliosis severity.

The objective of this study was to investigate how a new customizable light-curable osteosynthesis method (AdFix) compared to traditional metal hardware when loaded in torsion in an ovine phalanx model.

Twenty-one ovine proximal phalanges were given a 3mm transverse osteotomy and four 1.5mm cortex screws were inserted bicortically on either side of the gap. The light-curable polymer composite was then applied using the method developed by Hutchinson [1] to create osteosyntheses in two groups, having either a narrow (6mm, N=9) or a wide (10mm, N=9) fixation patch. A final group (N=3) was fixated with conventional metal plates. The constructs were loaded in torsion at a rate of 6°/second until failure or 45° of rotation was reached. Torque and angular displacement were measured, torsional stiffness was calculated as the slope of the Torque-Displacement curve, and maximum torque was queried for each specimen.

The torsional stiffnesses of the narrow, wide, and metal plate constructs were 39.1 ± 6.2, 54.4 ± 6.3, and 16.2 ± 3.0 Nmm/° respectively. All groups were statistically different from each other (p<0.001). The maximum torques of the narrow, wide, and metal plate constructs were 424 ± 72, 600 ± 120, and 579 ± 20 Nmm respectively. The narrow constructs were statistically different from the other two (p<0.05), while the wide and metal constructs were not statistically different from each other (p=0.76).

This work demonstrated that the torsional performance of the novel solution is comparable to metal fixators. As a measure of the functional range, the torsional stiffness in the AdhFix exceeded that of the metal plate. Furthermore, the wide patches were able to sustain a similar maximum toque as the metal plates. These results suggest AdhFix to be a viable, customizable alternative to metal implants for fracture fixation in the hand.

Due to their immunomodulatory and regenerative capacity, human bone marrow-derived mesenchymal stromal cells (hBMSCs) are promising in the treatment of polytrauma patients. However, few studies evaluated the effects of sera from polytraumatized patients on hBMSCs. The aim of this study was to explore changes in hBMSCs exposed to serum from polytrauma patients from different time points after trauma.

Sera from 84 patients on day 1 (D1), 5 (D5) and 10 (D10) after polytrauma (ISS ≥ 16) were pooled respectively to test the differential influence on hBMSC. As a control, sera from three healthy age- and gender-matched donors (HS) were collected. The pooled sera were analyzed by Multicytokine Array for pro-/anti-inflammatory cytokines. For the cell culture experiments, hBMSCs from four healthy donors were used. The influence of the different sera on hBMSC regarding cell proliferation, colony forming unit-fibroblast (CFU-F) assay, cell viability and toxicity, cell migration, as well as osteogenic and chondrogenic differentiation was analyzed. One-Way-ANOVA and LSD-test were used for the parametric, Kruskal-Wallis-test for non-parametric data. p≤0.05 was considered as statistically significant.

The results showed that D5 serum reduced hBMSCs cell proliferation capacity by 41.26% (p=0.000) compared with HS and increased the proportion of dead cells by 3.19% (p=0.008) and 2.25% (p=0.020) compared with D1 and D10. The frequency of CFU-F was reduced by 49.08% (p=0.041) in D5 and 53.99% (p=0.027) in D10 compared with HS, whereas the other parameters were not influenced.

The serological effect of polytrauma on hBMSCs was related to the time after trauma. It is disadvantageous to use BMSCs in polytraumatized patients five days after the incidence as obvious cytological changes could be found at that time point. However, it is promising to use hBMSCs to treat polytrauma after 10 days, combined with the concept of “Damage Control Orthopaedics” (DCO).

To quantify bone-nail fit in response to varying nail placements by entry point translation in straight antegrade humeral nailing using three-dimensional (3D) computational analysis

CT scans of ten cadaveric humeri were processed in 3D Slicer to obtain 3D models of the cortical and cancellous bone. The bone was divided into individual slices each consisting of 2% humeral length (L) with the centroid of each slice determined. To represent straight antegrade humeral nail, a rod consisting of two cylinders with diameters of 9.5mm and 8.5mm and length of 0.22L mm and 0.44L mm respectively joined at one end was modelled. The humeral head apex (surgical entry point) was translated by 1mm in both anterior-posterior and medio-lateral directions to generate eight entry points. Total nail protrusion surface area, maximum nail protrusion distance into cortical shell and top, middle, bottom deviation between nail and intramedullary cavity centre were investigated. Statistical analysis between the apex and translated entry points was conducted using paired t-test.

A posterior-lateral translation was considered as the optimal entry point with minimum protrusion in comparison to the anterior-medial translation experiencing twice the level of protrusion. Statistically significant differences in cortical protrusion were found in anterior-medial and posterior-lateral directions producing increased and decreased level of protrusion respectively compared to the apex. The bottom anterior-posterior deviation distance appeared to be a key predictor of cortical breach with the distal nail being more susceptible. Furthermore, nails with anterior translation generated higher anterior-posterior deviation (>4mm) compared to posterior translation (<3mm).

Aside from slight posterolateral translation of the entry point from the apex, inclusion of a distal posterior-lateral bend into current straight nail design could improve nail fitting within the curved humeral bone, potentially improving distal working length within the flat and narrow medullary canal of the distal humeral shaft.

Recent researches indicate that both M1 and M2 macrophages play vital roles in tissue repair and foreign body reaction processes. In this study, we investigated the dynamics of M1 macrophages in the induced membrane using a mouse femur critical-sized bone defect model.

The Masquelet method (M) and control (C) groups were established using C57BL/6J male mice (n=24). A 3mm-bone defect was created in the right femoral diaphysis followed by a Kirschner wire fixation, and a cement spacer was inserted into the defect in group M. In group C, the bone defect was left uninserted. Tissues around the defect were harvested at 1, 2, 4, and 6 weeks after surgery (n=3 in each group at each time point). Following Hematoxylin and eosin (HE) staining, immunohistochemical staining (IHC) was used to evaluate the CD68 expression as a marker of M1 macrophage. Iron staining was performed additionally to distinguish them from hemosiderin-phagocytosed macrophages.

In group M, HE staining revealed a hematoma-like structure, and CD68-positive cells were observed between the spacer and fibroblast layer at 1 week. The number of CD68-positive cells decreased at 2 weeks, while they were observed around the new bone at 4 and 6 weeks. In group C, fibroblast infiltration and fewer CD68-positive cells were observed in the bone defect without hematoma-like structure until 2 weeks, and no CD68-positive cells were observed at 4 and 6 weeks. Iron staining showed hemosiderin deposition in the surrounding area of the new bone in both groups at 4 and 6 weeks. The location of hemosiderin deposition was different from that of macrophage aggregation.

This study suggests that M1 macrophage aggregation is involved in the formation of induced membranes and osteogenesis and may be facilitated by the presence of spacers.

To conduct a meta-analysis for intertrochanteric hip fractures comparing in terms of efficacy and safety short versus long intralomedullary nails.

A pubmed search of the last 10 years for intertrochanteric fracture 31A1-31A3 according to the AO/OTA classification was performed. Baseline characteristics of each article were obtained, complication measures were analyzed: Peri-implant fracture, reoperations, deep/superficial infection, and mortality. Clinical variables consisted of blood loss (mL), length of stay (days), time of surgery (min) and nº of transfusions. Functional outcomes were also recorded. A meta-analysis was performed with Review Manager 5.4.

Twelve studies were included, nine were retrospective. The reoperations rate was lower in the short nail group and the peri-implant fracture rate was lower in the long nail group (OR 0.58, 95% CI 0.38 to 0.88) (OR 1.88, 95% CI 1.04 to 3.43). Surgery time and blood loss was significantly higher in the long nail group (MD −12.44, 95% CI −14.60 to −10.28) (MD −19.36, 95% CI −27.24 to −11.48). There were no differences in functional outcomes.

The short intramedullary nail has a higher risk of peri-implant fracture; however, the reoperation rate is lower compared to the long nail. Blood loss and surgery time was higher in the long nail group.

Total knee arthroplasty is one of the most common surgeries. About 92% of all implanted knee endorposthesis in 2020 were manufactured from uncoated CoCrMo articulating on ultra-high-molecular-weight polyethylene. All articluations generate wear particles and subsequent emission of metal ions due to the mechanical loading. These wear particles cause diverse negative reactions in the surrounding tissues and can lead to implant loosening. Coating technologies might offer the possibility to reduce this wear. Therefore, we investigated the applicability of tetrahedral amorphous carbon (ta-C) coating on CoCrMo alloy.

Polished specimens made of CoCrMo wrought alloy according to ISO 5832-12 were coated with ta-C coatings with different layer structure using pulsed laser deposition (PLD). This process allows the deposition of ta-C coatings with low internal stress using an additional relaxation laser. Surface quality and mechanical properties of the coating were characterised using optical surface measurements (NanoFocus μsurf expert, NanoFocus AG) and a nanoindentation tester NHT³ (Anton Paar GmbH). Scratch tests were performed on Micro Scratch Tester MST³ (Anton Paar TriTec SA) to define the coating adhesion. Pin-on-plate tribological tests, with a polyethylene ball sliding on the ta-C-coated plate under a defined load according to ISO 14243-1 were performed using a linear tribometer (Anton Paar GmbH) to evaluate the tribological and wear properties.

The ta-C coatings showed a mean roughness Ra of 5-20 nm and a hardness up to 60 GPa (n=3). The adhesion of the ta-C coatings (n=3) was comparable to the commercial coatings like TiN and TiNbN. The pin-on-plate tests showed an improvement of tribological properties in comparison with the polished uncoated CoCrMo specimens (n=3).

The ta-C coatings applied by DLP technology show increased hardness compared to the base material and sufficient adhesion. Further research will be needed to investigate the optimal coating strategy for implant coating.

Design of bone tissue engineering scaffolds imposes a number of requirements for their physical properties, in particular porosity and mechanical behaviour. Alginates are known as a potential material for such purposes, usually deploying calcium as a cross-linker. Calcium over-expression was reported having proinflammatory effect, which is not always desirable. Contrary to this, barium has better immunomodulatory outcome but data for barium as a cross-linker are scarce. In this work the objective was to produce Ba-linked alginates and compare their viscoelastic properties with Ca-linked controls in vitro.

Sodium alginate aqueous solution (1 wt%) with 0.03 wt.% CaCl₂ is gelled in dialysis tubing immersed in 27 mM CaCl₂ (controls) or BaCl₂, for 48 h, followed by freeze-drying and rehydration (with 0.3 wt.% CaCl₂ and 0.8 wt.% NaCl). Hydrogel discs (diameter 8-10 mm, thickness 4-6 mm) were assessed in dry and wet (DMEM immersed) states by dynamic mechanical analysis (DMA) under compressive creep conditions with increased loads, frequency scans and strain-controlled sweeps in physiological range (0.1-20 Hz) at 25°C and 37°C. Resulting data were analysed by conventional methods and by a model-free BEST (Biomaterials Enhanced Simulation Testing) to extract invariant values and material functions.

Significant differences were observed in properties of Ba-linked hydrogel scaffolds vs. Ca-linked controls. Specifically, for the similar porosity Ba-samples exhibited lower creep compliance, higher dynamical stiffness and lower loss factor in the whole studied range. Invariant modulus exhibited a non-linear decay vs. applied stress. These differences were observed in both dry and wet states and temperatures.

Use of barium as a cross-linker for alginates allows further modification of biomechanical properties of the scaffolds for better compliancy to the tissues in the application. Barium release might have an immunomodulating effect but also promote ion exchange for osteogenesis due to additional Ca/Ba concentration gradient.

Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This given study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or gas fluorination combined with the foam (F+coll). Cell free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, biomechanical properties, cell vitality and content, histopathology of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed.

Implantation of the scaffolds did not negatively affect mice weight development and organs, indicating biocompatibility. All scaffolds maintained their size and shape for the duration of the implantation. A high cell viability was detected in the scaffolds prior to and following implantation. Coll or F+coll scaffolds seeded with cells yielded superior macroscopic properties when compared to the controls. Mild signs of inflammation (foreign-body giant cells, hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable in vivo, elastic modulus, maximum force, tensile strength and strain at Fmax were significantly lower in the in vivo compared to the samples cultured 1 week in vitro, but did not differ between scaffold subtypes, except for a higher maximum force in F+coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering.

(shared first authorship)

Acknowledgement: The study was supported by DFG grants SCHU1979/9-1 and SCHU1979/14-1.

To ensure clinical relevance, the in vitro engineering of tissues for implantation requires artificial replacements to possess properties similar to native anatomy. Our overarching study is focussed on developing a bespoke bone-tendon in vitro model replicating the anatomy at the flexor digitorum profundus (FDP) tendon insertion site at the distal phalanx. Anatomical morphometric analysis has guided FDP tendon model design consisting of hard and soft tissue types. Here, we investigate potential materials for creation of the model's bone portion by comparison of two bone cements; brushite and genex (Biocomposites Ltd).

3D printed molds were prepared based on anatomical morphometric analysis of the FDP tendon insertion site and used to cast identical bone blocks from brushite and genex cements. Studies assessing the suitability of each cement type were conducted e.g. setting times, pH on submersion in culture medium and interaction with fibrin gels. Data was collected using qualitative imaging and qualitative measurements (N=3,n=6) for experimental conditions.

Both brushite (BC) and genex (GC) cements could be cast into bespoke molds, producing individual blocks and were mixed/handled with appropriate setting times. On initial submersion in culture medium, BC caused a reduction in pH values (7.49 [control]) to 6.85) while GC remained stable (7.59). Reduction in pH value also affected fibrin gel interaction where gel was seen to be detaching/not forming around BC and medium discolouration was noted. This was not observed in GC. While GC outperformed BC in initial tests, repeated washing of BC led to pH stabilisation (7.5,3xwashes), consistent with their further use in this model.

This study has compared BC and GC as materials for bone block production. Both materials show promise, and current work assessing material properties and cell proliferation are needed to inform our choice for use in our FDP-tendon-bone interface model.

This research was supported by an ORUK Studentship award (ref:533). Genex was kindly provided by Biocomposites, Ltd.

Meniscal tears are the most common injury in the knee, affecting 66/100,000 people/year. Surgical treatment includes arthroscopic meniscectomy or meniscal repair. Little is known regarding medium-term outcomes following these procedures in isolated meniscal tears. This study aims to quantitatively evaluate patients with meniscal tears, and those who have undergone meniscectomy and meniscal repair using validated patient reported outcome measures (PROMs), further exploring factors which affect surgical outcomes.

This observational study screened 334 patients who underwent arthroscopic surgery at South Tyneside Hospital since August 2013. 134 patients with isolated meniscal tears were invited to complete postal PROMs. A combination of patient notes and radiological imaging was used to collect information of interest including age, gender, knee-laterality, injured meniscus, tear pattern, procedure performed, complications, and associated injuries.

A total of 115 patients (pre-operative patients with current meniscal tear (n=36), meniscectomy (n=63), meniscal repair (n=16)) were included in the analysis with 96% successful PROM completion. Both meniscectomy and meniscal repairs (mean 55-months follow-up) showed better outcomes than pre-operative patients with meniscal tears. Meniscal repairs demonstrated superior outcomes across all PROMs when compared to meniscectomy, with a greater mean overall KOOS score of 17.2 (p=0.009). Factors including higher pre-operative Kellgren-Lawrence Grade, pre-operative articular cartilage lesions and bilateral meniscectomies were shown to negatively influence outcomes.

Both meniscectomy and meniscal repair maintain clinical benefit at mean 55-months follow-up, affirming their use for treatment of meniscal tears. When feasible, meniscal repair should be performed preferentially over meniscectomy in isolated meniscal tears. Identified predictive factors allow adequate treatment stratification in specific patient groups.

A hot swollen joint is a commonly encountered condition in clinical practice. With a broad range of differentials, septic arthritis (SA) is perhaps one of the most concerning. Treated by culture-specific antibiotics and arthroscopic lavage, some patients require multiple washouts. We aimed to determine:

(1) What are the risk factors for development of SA?

(2) What are the risk factors for repeat washout in SA patients?

(3) What are the important clinical differences between a periprosthetic joint infection (PJI) and SA cohort?

All patients presenting to the emergency department, orthopaedic, and rheumatology clinics between January 2020 to January 2021 with a hot, swollen joint were retrospectively evaluated. Patients with previous trauma on the ipsilateral joint, with data missing from their medical records in any of the variables required for analysis, <24 months follow-up were excluded.

Variables of interest in the three-month period preceding the diagnosis of SA were compared between SA and non-SA patients. Factors with a p-value of p<0.100 in univariate analysis were included in a stepwise multivariate logistic regression model. Similar analyses were performed to compare SA patients with multiple washouts with those needing one washout. Demographical and clinical data for PJI patients were collected to delineate important differences with SA cohort.

211 patients were included (SA:28;PJI:24;pseudogout:32;gout:26;others:101). Multivariate analysis showed rheumatoid arthritis (RA), skin infection, and liver disease were risk factors for SA. Amongst patients with septic arthritis, multivariate analysis showed that WBC levels above normal limits (3.6-10.5×109 cells/L) and RA were risk factors for multiple washouts.

Between the SA and PJI cohorts, BMI (p=0.002) was significantly lower in the former, whilst WBC level (p=0.023) and CRP (p<0.0001) was significantly higher in the former.

Early diagnosis of septic arthritis requires understanding the risk factors, namely RA, skin infection, and liver disease. Considering PJI and septic arthritis as the same entity can lead to wrong clinical judgement, and clinicians should be aware of important differences. We believe that the models in this study are of prognostic value to clinicians who are presented with the common presenting compliant of a hot swollen joint.

In this study, we aimed to investigate tibiofemoral and allograft loading parameters after OCA transplantation using tibial plateau shell grafts to characterize the clinically relevant biomechanics that may influence joint kinematics and OCA osseointegration after transplantation. The study was designed to test the hypothesis that there are significant changes in joint loading after tibial plateau OCA transplantation that may require unique post-operative rehabilitation regimens in patients to restore balance in the knee joint.

Fresh-frozen cadaveric knees (n=6) were thawed and mounted onto a 6 DOF KUKA robot. Specimens were size matched to +2 mm for the medial-to-lateral width of the medial tibial hemiplateaus. Three specimens served as allograft recipient knees and three served as donor knees. Recipient knees were first tested in their native state and then tested with size-matched medial tibial hemiplateau shell grafts (n=3) prepared from the donor knees using custom-cut tab-in-slot and subchondral drilling techniques. Tekscan sensors were placed in the joint spaces to evaluate the loading conditions under 90N biaxial loading at full extension of the knee before and after graft placement. The I-Scan system used in conjunction analyzed the total force, pressure distribution, peak pressure, and center of force within the joint space.

Data demonstrated significant difference (p<0.05) in joint space loading after graft implantation compared to controls in both lateral and medial tibial plateaus. The I-Scan pressure mapping system displayed changes in femoral condylar contact points as well.

The results demonstrated that joint space loading was significantly different (p<0.05) between all preoperative and postoperative cadaveric specimens. Despite the best efforts to size match grafts, slight differences in the host's joint geometry resulted in shifts of contact areas between the tibial plateau and femoral condyle therefore causing either an increase or decrease in pressure measured by the sensor. This concludes that accuracy in graft size matching is extremely important to restoring close to normal loading across the joint and this can be further ensured through postoperative care customized to the patient after OCA surgery.

Osteoarthritis, the most common degenerative joint disease, significantly impairs life quality and labor capability of patients. Synovial inflammation, initiated by HMGB1 (High mobility group box 1)-induced activation of macrophage, precedes other pathological changes. As an upstream regulator of NF-κB (nuclear factor-kappa B) and MAPK (mitogen-activated protein kinase) signaling pathway, TAK1 (TGF-β activated kinase 1) participates in macrophage activation, while its function in osteoarthritis remains unveiled. This study aims to investigate the role of TAK1 in the pathogenesis of osteoarthritis via both in vitro and in vivo approaches.

We performed immunohistochemical staining for TAK1 in synovial tissue, both in osteoarthritis patients and healthy control. Besides, immunofluorescence staining for F4/80 as macrophage marker and TAK1 were conducted as well. TAK1 expression was examined in RAW264.7 macrophages stimulated by HMGB1 via qPCR (Quantitative polymerase chain reaction) and Western blotting, and the effect of TAK1 inhibitor (5z-7 oxozeaenol) on TNF-α production was evaluated by immunofluorescence staining. Further, we explored the influence of intra-articular shRNA (short hairpin RNA) targeting TAK1 on collagenase-induced osteoarthritis in mice.

Immunohistochemical staining confirmed significant elevation of TAK1 in osteoarthritic synovium, and immunofluorescence staining suggested macrophages as predominant residence of TAK1. In HMGB1-stimulated RAW264.7 macrophages, TAK1 expression was up-regulated both in mRNA and protein level. Besides, TAK1 inhibitor significantly impairs the production of TNF-α by macrophages upon HMGB1 stimulation. Moreover, intra-articular injection of lentivirus loaded with shRNA targeting TAK1 (sh-TAK1) reduced peri-articular osteophyte formation in collagenase-induced osteoarthritis in mice.

TAK1 exerts a potent role in the pathogenesis of osteoarthritis by mediating the activation of macrophages.

Periprosthetic joint infections (PJI) are one of the most common reasons for orthopedic revision surgeries. In previous studies, it has been shown that silver modification of titanium (Ti-6Al-4V) surfaces by PMEDM (powder mixed electrical discharge machining) has an antibacterial effect on Staphylococcus aureus adhesion. Whether this method also influences the proliferation of bacteria has not been investigated so far. Furthermore, the effect is only limitedly investigated on the ossification processes. Therefore, the aim of this work is to investigate the antibacterial effect as well as the in vitro ossification process of PMEDM machined surfaces modified by integration of silver.

In this study, we analyzed adhesion and proliferation of S. aureus in comparison to of surface roughness, silver content and layer thickness of the silver-integrated-PMEDM surfaces (N = 5). To test the in vitro ossification, human osteoblasts (SaOs-2) and osteoclasts (differentiated from murine-bone-marrow-macrophages) were cultured on the silver surfaces (N = 3).

We showed that the attachment of S. aureus on the surfaces was significantly lower than on the comparative control surfaces of pure Ti-6Al-4V without incorporated silver, independently of the measured surface properties. Bacterial proliferation, however, was not affected by the silver content. No influence on the in vitro ossification was observed, whereas osteoclast formation was drastically reduced on the silver-modified surfaces.

We showed that 1 to 3% of silver in the surface layer significantly reduced the adhesion of S. aureus, but not the proliferation of already attached bacteria. At the same time, no influence on the in vitro ossification was observed, while no osteoclasts were formed on the surface. Therefore, we state that PMEDM with simultaneous silver modification of the machined surfaces represents a promising technology for endoprostheses manufacturing to reduce infections while at the same time optimizing bone ingrowth.

The implantation of endoprosthesis is a routine procedure in orthopaedics. Endoprosthesis are mainly manufactured from ceramics, polymers, metals or metal alloys. To ensure longevity of the implants they should be as biocompatible as possible and ideally have antibacterial properties, to avoid periprosthetic joint infections (PJI). Various antibacterial implant materials have been proposed, but have so far only been used sporadically in patients. PJI is one of the main risk factors for revision surgeries. The aim of the study was to identify novel implant coatings that both exhibit antibacterial properties whilst having optimal biocompatibility.

Six different novel implant coatings and surface modifications (EBM TiAl6V4, strontium, TiCuN, TiNbN, gentamicin phosphate (GP), gentamicin phosphate+cationic polymer (GP+CP)) were compared to standard CoCrMo-alloy. The coatings were further characterized with regard to the surface roughness. E. coli and S. capitis were cultured on the modified surfaces to investigate the antibacterial properties. To quantify bacterial proliferation the optical density (OD) was measured and viability was determined using colony forming units (CFU). Murine bone marrow derived macrophages (BMMs) were cultured on the surfaces and differentiated into osteoblasts to quantify the mineralisation using the alizarin red assay.

All novel coatings showed reduced bacterial proliferation and viability compared to standard CoCrMo-alloy. A significant reduction was observed for GP and GP+CP coated samples compared to CoCrMo (OD_GP,E.coli = 0.18±0.4; OD_GP+CP,E.coli = 0.13±0.3; p≤0.0002; N≥7-8). An increase in osteoblast-mediated mineralisation was observed on all surfaces tested compared to CoCrMo. Furthermore, GP and GP+CP coated samples showed a statistically significant increase (M_GP = 0.21±0.1; M_GP+CP = 0.25±0.2; p<0.0001; N≥3-6).

The preliminary data indicates that the gentamicin containing surfaces have the most effective antibacterial property and the highest osseointegrative capacity. The use of antibiotic coatings on prostheses could reduce the risk of PJI while being applied on osseointegrative implant surfaces.

Recently, several smartphone applications (apps) have been developed and validated for ankle ROM measurement tools like the universal goniometer. This is the first innovative study introduces a new smartphone application to measure ankle joint ROM as a remote solution. This study aimed to assess the correlation between smartphone ROM and universal goniometer measurements, and also report the evaluation of the DijiA app by users.

The study included 22 healthy university students (14F/8M; 20.68±1.72 years) admitted to Yeditepe University. Fourty four feet was measured by both the universal goniometer (UG) and DijiA app. The datas were analyzed through using the intraclass correlation coefficient (ICC). The DijiA app was evaluated by usability testing with representative users.

Pearson correlation coefficient test showed moderate correlation between the DijiA and UG for dorsiflexion (DF) and plantar flexion (PF) measurements (Pearson correlation coefficient: r=0.323, for DF; r=0.435 for PF 95% confidence interval). The application usability was found as high with 76.5 average score and users liked it.

The DijiA app may be a more convenient and easy way to measure ankle DF and PF-ROM than UG. It can be used to evaluate ROM in clinical practice or home using as a personal smartphone.

C. Difficile infections in elderly patients with hip fractures is associated with high morbidity and mortality. Antibiotic regimens with penicillin and its derivatives is a leading cause. Antibiotic prophylactic preferences vary across different hospitals within NHS. We compared two antibiotic prophylactic regimens - Cefuroxime only prophylaxis and Teicoplanin with Gentamicin prophylaxis in fracture neck of femur surgery, and evaluated the incidence of C. Difficile diarrhea and Surgical Site Infection (SSI).

To assess the Surgical Site Infection and C. Difficile infection rate associated with different regimens of antibiotics prophylaxis in fracture neck of femur surgery.

Data was analyzed retrospectively. Neck of femur fracture patients treated surgically from 2009 in our unit were included. Age, gender, co morbidities, type of fracture, operation, ASA grade was collected. 1242 patients received Cefuroxime only prophylaxis between January 2009 and December 2012 (Group 1) and 486 patients received Teicoplanin with Gentamicin between October 2015 and March 2017 (Group 2). There were 353 males and 889 female patients in Group 1 and 138 males and 348 female patients in Group 2. The co morbidities in both groups were comparable. Incidence of C. Difficile diarrhea and Surgical Site Infection (SSI) was noted. Statistical analysis with chi square test was performed to determine the ‘p’ value.

C. Diff diarrhea rate in Group 2 was 0.41 % as compared to 1.29 % in Group 1. The Surgical Site Infection (SSI) rate in Group 2 was 0.41 % as compared to 3.06 % in Group 1. The comparative results were statistically significant (p = 0.0009).

Prophylactic antibiotic regimen of Teicoplanin with Gentamicin showed significant reduction in C. Difficile diarrhea & Surgical Site Infection in fracture neck of femur patients undergoing surgery.

Cannulated hip screws are frequently used in the management of hip fractures. There have been concerns over the failure rate of the technique and the outcomes of those that subsequently require conversion to total hip replacement (THR).

This study utilised a database of over 600 cannulated hip screw (CHS) fixations performed over a 14-year period and followed up for a minimum of one year (1-14). We identified 57 cases where a conversion to THR took place (40 females, 17 males, mean age: 71.2 years). Patient demographics, original mechanism of injury, fracture classification, reason for fixation failure, time until arthroplasty, implant type and post-arthroplasty complications were recorded. Clinical outcomes were measured using the Oxford Hip Score.

The failure rate of cannulated screw treatment was 9.4% and the mean time from initial fixation to arthroplasty was 15.4 (16.5) months. Thirty six fractures were initially undisplaced and 21 were displaced. As one might expect the displaced cases tended to be younger but this didn't reach statistical significance [66.5(14.3) vs 72.7(13.1), p=0.1]. The commonest causes of failure were non-union (25 cases, 44%) and avascular necrosis (17 cases, 30%). Complications after THR consisted of one leg length discrepancy and one peri-prosthetic fracture. The mean Oxford score pre-arthroplasty was 12.2 (8.4), improving to 38.4 (11.1) at one-year. Although the pre op Oxford scores tended to be lower in patients with undisplaced fractures and higher ASA scores, the improvement was the same whatever the pre-op situation. The one-year Oxford score and the improvement in score are comparable to those seen in the literature for THR in general.

In conclusion, CHS has a high success rate and where salvage arthroplasty is required it can provide good clinical outcomes with low complication rates.

Total hip replacement (THR) is indicated for patients with osteoarthritis where conservative treatment has failed. Metal alloys used in THR implants such as cobalt-chromium (CoCr) have been known to cause pro-inflammatory reactions in patients, therefore leading to the need for costly revision surgery. This study therefore aimed to investigate the role of TLR4 in the activation of a human osteoblast model in response to CoCr particles in vitro.

Human osteoblasts (MG-63 cell line) were seeded at a density of 100,000 cells and treated with 0.5, 5, 50mm3 CoCr particles per cell for 24-hours. Trypan blue and the XTT Cell Proliferation Kit II were then used in conjunction with the cells to assess CoCr-induced cytotoxicity. Cells were pre-treated with a commercially available TLR4-specific small molecule inhibitor (CLI-095) for 6 hours. Untreated cells were used as a negative control and lipopolysaccharide (LPS) was used as a positive control. Following treatment the cell supernatant was collected and used for enzyme-linked immunosorbant assay (ELISA) to measure the secretion of interleukin-8 (IL-8), CXCL10, and interleukin-6 (IL-6).

Trypan blue and XTT analysis showed that there was no significant changes to cell viability or proliferation at any dose used of CoCr after 24 hours. There was a significant increase in protein secretion of IL-8 (p<0.001), CXCL10 (p<0.001), and IL-6 (p<0.001) in the cells which received the highest dosage of CoCr. This pro-inflammatory secretory response was ameliorated by TLR4 blockade (p<0.001).

CoCr particles are not cytotoxic to osteoblasts but they do induce pro-inflammatory changes as characterised by increased secretion of chemokines IL-8, CXCL10, and IL-6. These responses occur via a TLR4-mediated pathway and upon inhibition they can be effectively ameliorated. This is particularly important as TLR4 could be a potential target for pharmacological intervention used in patients experiencing immunological reactions to metal implant debris.

Plantar fasciitis (PF) is one of the widespread conditions causing hindfoot pain. The most common presenting symptoms are functional limitation and pain (first step and activity) on plantar surface of the foot. The non-operative treatments provide complete resolution of pain in 90% of patients, but functional limitation still remains as a risk factor for recurrency of PF. Although the number of non-operative treatment options showing efficacy on pain and functional limitation are excessive, the evidences are limited for functional limitation. Additionally, Mulligan mobilization with movement (MMWM) in Chronic Plantar Fasciitis has been poorly studied in the literature. According to these findings, the study was aimed to determine effectiveness of Mulligan mobilization with movement on Chronic Plantar Fasciitis.

A total of 25 patients (40 feet) with chronic PF were included in the study. The patients were randomly divided into Mulligan concept rehabilitation group (PF-M, n=20 feet) and Home Rehabilitation group (PF-H, n=20 feet). (MMWM), Foot and ankle exercises program were applied to PF-M, twice a week totally 8 week (16 sessions) and foot- ankle exercises as a home program were given for PF-H, 8 weeks. The range of motion (ROM) for dorsiflexion and plantar flexion was measured by using a manual goniometer. Pain, disability and activity restriction were assessed by Foot Function Index (FFI) . The first step morning pain was evaluated by Visual Analogue Scale (VAS) and Kinesiophobia was also reported by using Tampa Scale (TSK). Patients were evaluated at baseline and 8 weeks.

FFI, VAS, TSK, ROM values improved in all groups (intragroup variability) at 8th week (P < .05). The other result indicated that ROM values for DF and PF and TSK scores in PF-M had more significant improvement than PF-H (p<.05).

To the best of our knowledge this is the first randomised controlled trial for investigating Mulligan Concept efficiancy on chronic PF. Both Mulligan mobilization with movement (MMWM) and exercise protocols are effective for chronic PF. Furthermore, The Mulligan concept seems more effective treatment option in reducing kinesiophobia and improving functional capacity.

An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA) pathophysiology remains largely unexplored. This study aimed to compare the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF).

Flow cytometric analysis, protein level measurements (ELISA), NEU oxidative burst assays, detection of NEU phagocytosis (pHrodo^TM Green Zymosan Biparticles^TM Conjugate for Phagocytosis), morphological analysis of the SF-derived/synovial tissue NEUs, and cultivation of human umbilical vein endothelial cells (HUVECs) using SF supernatant were used to characterise NEUs functionally/morphologically.

Results: Compared with INF NEUs, KOA NEUs were characterised by a lower expression of CD11b, CD54 and CD64, a higher expression of CD62L, TLR2 and TLR4, and lower production of inflammatory mediators and proteases, except CCL2.

Functionally, KOA NEUs displayed an increased production of radical oxygen species and phagocytic activity compared with INF NEUs. Morphologically, KOA and INF cells displayed different cell sizes and morphology, histological characteristics of the surrounding synovial tissues and influence on endothelial cells. KOA NEUs were further subdivided into two groups: SF containing <10% and SF with 10%–60% of NEUs. Analyses of two KOA NEU subgroups revealed that NEUs with SF <10% were characterised by 1) higher CD54, CD64, TLR2 and TLR4 expression on their surface; 2) higher concentrations of TNF-α, sTREM-1, VILIP-1, IL-1RA and MMP-9 in SFs.

Our findings reveal a key role for NEUs in the pathophysiology of KOA, indicating that these cells are morphologically and functionally different from INF NEUs. Further studies should explore the mechanisms that contribute to the increased number of NEUs and their crosstalk with other immune cells in KOA.

This study was supported by the Ministry of Health of the Czech Republic (NU20-06-00269; NU21-06-00370).

Odontoid fracture of the second cervical vertebra (C2) is the most common spinal fracture type in elderly patients. However, very little is known about the biomechanical fracture mechanisms, but could play a role in fracture prevention and treatment. This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process.

A total of 42 human C2 specimens (14 female and 28 male, 71.5 ± 6.5 years) were scanned via quantitative computed tomography, divided in 6 groups (n = 7) and subjected to combined quasi-static loading at a rate of 0.1 mm/s until fracturing at inclinations of −15°, 0° and 15° in sagittal plane, and −50° and 0° in transverse plane. Bone mineral density (BMD), specimen height, fusion state of the ossification centers, stiffness, yield load, ultimate load, and fracture type according to Anderson and d'Alonzo were assessed.

While the lowest values for stiffness, yield, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences could be observed among the six groups (p = 0.235, p = 0.646, and p = 0.505, respectively). Evaluating specimens with only clearly distinguishable fusion of the ossification centers (n = 26) reveled even less differences among the groups for all mechanical parameters. BMD was positively correlated with yield load (R² = 0.350, p < 0.001), and ultimate load (R² = 0.955, p < 0.001), but not with stiffness (p = 0.070). Type III was the most common fracture type (23.5%).

These biomechanical outcomes indicate that load direction plays a subordinate role in traumatic fractures of the odontoid process in contrast to BMD which is a strong determinant of stiffness and strength. Thus, odontoid fractures appear to result from an interaction between load magnitude and bone quality.

Tip-apex distance (TAD) has long been discussed as a metric for determining risk of failure in fixation of peritrochanteric hip fractures. This study seeks to investigate risk factors including TAD for hospital readmission one year after hip fixation surgery.

A retrospective review of proximal hip fractures treated with single screw intramedullary devices between 2016 and 2020 was performed at a 327 bed regional medical center. Patients included had a postoperative follow-up of at least twelve months or surgery-related complications developing within that time.

44 of the 67 patients in this study met the inclusion criteria with adequate follow-up post-surgery. The average TAD in our study population was 19.57mm and the average one year readmission rate was 15.9%. 3 out of 6 patients (50%) with a TAD > 25mm were readmitted within one year due to surgery-related complications. In contrast, 3 out of 38 patients (7.9%) with a TAD < 25mm were readmitted within one year due to surgery-related complications (p=0.0254). Individual TAD measurements, averaging 22.05mm in patients readmitted within one year of surgery and 19.18mm in patients not readmitted within one year of surgery were not significantly different between the two groups (p=0.2113).

Our data indicate a significant improvement in hospital readmission rates up to one year after hip fixation surgery in patients with a TAD < 25mm with a decrease in readmissions of over 40% (50% vs 7.9%). This result builds upon past investigations by extending the follow-up time to one year after surgery and utilizing hospital readmissions as a metric for surgical success. With the well-documented physical and financial costs of hospital readmission after hip surgery, our study highlights a reduction of TAD < 25mm as an effective method of improving patient outcomes and reducing financial costs to patients and medical institutions.

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence.

Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated.

The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells.

Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection.

Results in patients undergoing total hip arthroplasty (THA) for femoral head osteonecrosis (ON) when compared with primary osteoarthritis (OA) are controversial. Different factors like age, THA type or surgical technique may affect outcome. We hypothesized that patients with ON had an increased revision rate compared with OA. We analysed clinical outcome, estimated the survival rate for revision surgery, and their possible risk factors, in two groups of patients.

In this retrospective cohort analysis of our prospective database, we assessed 2464 primary THAs implanted between 1989 and 2017. Patients with OA were included in group 1, 2090 hips; and patients with ON in group 2, 374 hips. In group 2 there were more men (p<0.001), patients younger than 60 years old (p<0.001) and with greater physical activity (p<0.001). Patients with lumbar OA (p<0.001) and a radiological acetabular shape type B according to Dorr (p<0.001) were more frequent in group 1. Clinical outcome was assessed according to the Harris Hip Score and radiological analysis included postoperative acetabular and femoral component position and hip reconstruction. Kaplan-Meier survivorship analysis was used to estimate the cumulative probability of not having revision surgery for different reasons. Univariate and multivariate Cox regression models were used to assess risk factors for revision surgery.

Clinical improvement was better in the ON at all intervals. There were 90 hips revised, 68 due to loosening or wear, 52 (2.5%) in group 1, and 16 (4.3%) in group 2. Overall, the survival rate for revision surgery for any cause at 22 years was 88.0 % (95% CI, 82-94) in group 1 and 84.1% (95% CI, 69 – 99) in group 2 (p=0.019). Multivariate regression analysis showed that hips with conventional polyethylene (PE), compared with highly-cross linked PEs or ceramic-on-ceramic bearings, (p=0.01, Hazard Ratio (HR): 2.12, 95% CI 1.15-3.92), and cups outside the Lewinnek´s safe zone had a higher risk for revision surgery (p<0.001, HR: 2.57, 95% CI 1.69-3.91).

Modern highly-cross linked PEs and ceramic-on-ceramic bearings use, and a proper surgical technique improved revision rate in patients undergoing THA due to ON compared with OA.

Herein we address, hyaline cartilage regeneration issue by engineering a synthetic biocompatible hydrogel scaffold capable to promote chondrogenic differentiation. In this study, the chemically crosslinked hydrogels consisting of synthetic peptides that have the collagen-like sequence Cys-Gly-(Pro-Lys-Gly)4 (Pro-Hyp-Gly)4 (Asp-Hyp-Gly)4- conjugated with RGD sequence (CLP-RGD) and crosslinked hydrogels of type I collagen (CA) were used. For cartilage formation, we used human skeletal muscle-derived stem/progenitor cells (hMDSPCs) set for differentiation towards a chondrogenic lineage by BMP-7 and TGF-ß3 growth factors.

Initially 150, 100 and 75 ng of BMP-7and TGF-ß3 growth factors were inserted in each scaffold and amount of growth factors diffusing out of the scaffolds was observed by ELISA assays. In vitro experiments were performed by seeding hMDSPCs onto hydrogels loaded with growth factors (75ng/scaffold) and cultured for 28 days. Cartilage formation was monitored by ELISA and RT-PCR assays. All experiments were performed in triplicates or quadruplicates.

Growth factors incorporation strategy allowed a sustained release of TGF-ß3 growth factor, 6.00.3% of the initially loaded amount diffused out after 4 h and 2.70.5% already at the second time point (24h) from CA and CLP-RGD substrates. For the BMP-7 growth factor, 13.12.3% and 15.751.6% of the initially loaded amount diffused out after 4 h, 1.70.2% and 2.450.3% at the second time point (24 h) from CA and CLP-RGD respectively. In vitro experiments shown that scaffolds with immobilized growth factors resulted in higher collagen type II accumulation when compared to the scaffolds alone. The gene expression on CLP-RGD hydrogels with growth factors has shown lower collagen type I expression and higher aggrecan expression compared to day 0. However, we also report increased collagen X gene expression on CA hydrogels (with growth factors).

Our results support the potential of the strategy of combining hydrogels functionalized with differentiation factors toward improving cartilage repair.

There remains much debate regarding the optimal method for surgical management of patients with long head of biceps pathology. The aim of this study was to compare the outcomes of tenotomy versus tenodesis.

This systematic review and meta-analysis was registered on PROSPERO (ref: CRD42020198658). Electronic databases searched included EMBASE, Medline, PsycINFO, and Cochrane Library. Randomized controlled trials (RCTs) comparing tenotomy versus tenodesis were included. Risk of bias within studies was assessed using the Cochrane risk of bias v2.0 tool and the Jadad score. The primary outcome included patient reported functional outcome measures pooled using standardized mean difference (SMD) and a random effects model. Secondary outcome measures included pain (visual analogue scale VAS), rate of Popeye deformity, and operative time.

860 patients from 11 RCTs (426 tenotomy vs 434 tenodesis) were included in the meta-analysis. Pooled analysis of all PROMs data demonstrated comparable outcomes between tenotomy vs tenodesis (SMD 0.14, 95% CI −0.04 to 0.32; p=0.13). Sensitivity analysis comparing RCTs involving patients with and without an intact rotator cuff did not change the primary outcome. There was no significant difference for pain (VAS). Tenodesis resulted in a lower rate of Popeye deformity (OR 0.29, 95% CI 0.19 to 0.45, p < 0.00001). Tenotomy demonstrated a shorter operative time (MD 15.21, 95% CI 1.06 to 29.36, p < 0.00001).

Aside from a lower rate of cosmetic deformity, tenodesis yielded no measurable significant benefit to tenotomy for addressing pathology in the long head of biceps. A large multi-centre clinical effectiveness randomised controlled trial is needed to provide clarity in this area.

Silk fibroin (SF) has been used as a scaffold for cartilage tissue engineering. Different silkworms strain produced different protein. Also, molecular weight of SF depends on extraction method. We hypothesised that strain of silkworm and method of SF extraction would effect biological properties of SF scaffold. Therefore, cell viability and chondrogenic gene expression of human chondrogenic progenitor cells (HCPCs) treated with SF from 10 silkworm strains and two common SF extraction methods were investigate in this study.

Twenty g of 10 strains silk cocoons were separately degummed in 0.02M Na2CO3 solution and dissolved in 100๐C for 30 minutes. Half of them were then dissolved in CaCl2/Ethanol/H2O [1:2:8 molar ratio] at 70±5๐C (method 1) and other half was dissolved in 46% w/v CaCl2 at 105±5๐C (method 2) for 4 hours. HCPCs were cultured in SF added cultured medial according to strain and extraction method. Cell viability at day 1, 3, and 7, were determined. Expression of collagen I, collagen II, and aggrecan at day 7 and 14, was studied. All experiment were done in triplicated samples.

Generally, method 1 SF extraction showed higher cell viability in all strains. Cell viability from Nanglai Saraburi, Laung Saraburi and Nangtui strains were higher than those without SF in every time point while Wanasawan and J108 had higher viability at day 1 and decreased by time. Expression in collagen 1, collagen 2 and aggrecan in method 1 are higher at day 7 and day 14. Collagen 1 expression was highest in Nangnoi Srisaket, followed by Laung Saraburi and Nanglai Saraburi in day 7. Nangnoi Srisaket also had highest expression at day 14, followed by Nanglai Saraburi and Laung Saraburi respectively. Nangseaw had highest collagen 2 expression, follow by Laung Saraburi and Nangnoi Srisaket respectively. Higher aggrecan gene expression of Tubtimsiam, Wanasawan, UB 1 and Nangnoi Srisaket was observed at day 7 and increased expression of all strains at day 14.

SF extraction using CaCl2/Ethanol/H2O offered better cell viability and chondrogenic expression. Nangseaw, Laung Saraburi and Nangnoi Srisaket strains expressed more chondrogenic phenotype.

Dual mobility (DM) total hip replacements (THRs) were introduced to reduce dislocation risk, which is the most common cause of early revision. Although DM THRs have shown good overall survivorship and low dislocation rates, the mechanisms which describe how these bearings function in-vivo are not fully understood. Therefore, the study aim was to comprehensively assess retrieved DM polyethylene liners for signs of damage using visual inspection and semi-quantitative geometric assessment methods.

Retrieved DM liners (n=18) were visually inspected for the presence of surface damage, whereby the internal and external surfaces were independently assigned a score of one (present) or zero (not present) for seven damage modes. The severity of damage was not assessed. The material composition of embedded debris was characterised using energy-dispersive x-ray analysis (EDX). Additionally, each liner was geometrically assessed for signs of wear/deformation [1].

Scratching and pitting were the most common damage modes on either surface. Additionally, burnishing was observed on 50% of the internal surfaces and embedded debris was identified on 67% of the external surfaces. EDX analysis of the debris identified several materials including titanium, cobalt-chrome, iron, and tantalum. Geometric analysis demonstrated highly variable damage patterns across the liners.

The incidence of burnishing was three times greater for the internal surfaces, suggesting that this acts as the primary articulation site. The external surfaces sustained more observable damage as evidenced by a higher incidence of embedded debris, abrasion, delamination, and deformation. In conjunction with the highly variable damage patterns observed, these results suggest that DM kinematics are complex and may be influenced by several factors (e.g., soft tissue fibrosis, patient activities) and thus further investigation is warranted.

The primary purpose of this longitudinal study was to examine the impact of physical and mental well-being on a successful return to work after cartilage or ligament knee injury. A secondary purpose was to examine the effectiveness of our program regarding ordering imaging (plain X-rays, US, MRI, CT scan), and the impact that costly investigations made in clinical management.

Workers who had sustained a work-related knee injury and were assessed at the lower extremity specialty clinic of our hospital program were followed up until they were discharged. All patients completed the numeric pain rating scale (NPRS), the Lower Extremity Functional Scale (LEFS), and the Hospital Anxiety and Depression Scale (HADS) on the initial assessment and at final follow-up.

We included 30 patients, mean age, 50(9), 11(37%) females, 19(63%) males. The most common mechanisms of injury were twisting (13, 45%) and falls (12, 41%). The knee injuries included 10 anterior collateral ligament (ACL), 3 posterior collateral ligament (PCL), 19 medical and lateral ligament injuries, and 22 meniscus injuries with some injuries overlapping. Ten patients (30%) underwent surgery (8 meniscectomy, two ligamentous repairs).

Patients showed improvement in pain scores (p<0.0001) and the LEFS scores (p=0.004). Seventeen patients (57%) returned to full-time work and 11 (37%) were not working at the time of discharge with one patient performing part-time work, and one on re-training. Higher levels of pre (p=0.02) and post-treatment (p=0.03) depression and post-treatment anxiety (p=0.02) had a negative impact on a successful return to work. Most clients had proper investigations ordered by their family physicians in the community (24 plain x-rays, 11 US, and 21 MRI). Our team ordered only 6 plain x-rays and 6 new MRI.

We found significant improvement in pain and disability in injured workers who received an expedited multidisciplinary care. Anxiety and depression were the most important predictors of poorer recovery and a less successful work status. The judicious use of costly imaging is expected to reduce the overall health care cost of an injury, while providing new important information such as adding a new diagnosis or changing the management.

Our study seeks to determine whether characteristics of radiographs taken post-reduction of a forearm fracture can indicate future risk of refracture or loss of reduction. We hypothesize that reducing forearm fractures too precisely may be counterproductive and provide less benefit than reductions left slightly offset prior to cast immobilization.

We conducted a retrospective review of 1079 pediatric patients treated for forearm fractures between January 2014 and September 2021 in a 327 bed regional medical center. Percent fracture displacement, location, orientation, comminution, fracture line visibility and angle of angulation were determined by AP and lateral radiographs. Percent fracture displacement was derived by: (Displacement of Bone Shafts / Diameter) x 100% = %Fracture Displacement.

Patients treated with closed reduction were reduced from a mean displacement of 29.26±36.18% at an angulation of 22.67±16.57 degrees to 7.88±9.07% displacement and 3.89±6.68 degrees angulation post-reduction. Patients developing complications including a loss of reduction or refracture were found to have post-operative radiographs with a lower percent displacement (0.50±1.12) than those not developing complications (8.65±9.21)(p=0.0580). Post-reduction angulation (p=1.000), average reduction in angulation (p=1.000) and average reduction in displacement percent(p=0.2102) were not significantly associated with development of complications.

Percent displacement of radial shafts was seen to be the most important metric to monitor in post-operative radiographs for patients undergoing closed reduction of a forearm fracture. We theorize a slight displacement provides greater surface area for osteoblastic expansion and callus formation leading to a decreased risk of refracture or loss of reduction. While our sample size precludes our ability to measure the ideal amount of post-reduction displacement for optimal healing, our results demonstrate that some degree of shaft displacement is required for optimal healing conditions.

This study was conducted to investigate the characteristics, complications, radiologic features and clinical course of patients undergoing reduction of forearm fractures in order to better inform patient prognosis and postoperative management.

We conducted a retrospective cohort study of 1079 pediatric patients treated for forearm fractures between January 2014 and September 2021 in a 327 bed regional medical center. A preoperative radiological assessment and chart review was performed. Percent fracture displacement, location, orientation, comonution, fracture line visibility and angle of angulation were determined by AP and lateral radiographs. Percent fracture displacement was derived by: (Displacement of Bone Shafts / Diameter) x 100% = %Fracture Displacement. Angle of angulation and percent fracture displacement were calculated by averaging AP and lateral radiograph measurements.

80 cases, averaging 13.5±8.3 years, were identified as having a complete fracture of the radius and/or ulna with 69 receiving closed reduction and 11 receiving fixation via an intramedullary device or percutaneous pinning. Eight patients (10%) experienced complications with four resulting in a refracture and four resulting in significant loss of reduction (LOR) without refracture. Fractures in the proximal ⅔s of the radius were associated with a significant increase in complications compared to fractures in the distal ⅓ of the radius (31.6% vs 3.4%) (P=.000428). Likewise, a higher percent fracture displacement was associated with a decreased risk of complications (28.7% vs 5.9% displacement)(P=0.0403). No elevated risk of complications was found based on fracture orientation, angulation, fracture line visibility, forearm bone(s) fractured, sex, age or arm affected.

Our result highlights radius fracture location and percent fracture displacement as markers with prognostic value following forearm fracture. These measurements are simply calculated via pre-reduction radiographs, providing an efficient method of informing risk of complications following forearm fracture.

The efficacy of saline irrigation for the treatment of periprosthetic infection (PJI) is limited in the presence of infected implants. This study evaluated the efficacy of vancomycin/tobramycin-doped polyvinyl alcohol (PVA)/ceramic composites (PVA-VAN/TOB-P) after saline irrigation in a mouse pouch infection model.

3D printed porous titanium (Ti) cylinders (400, 700 and 100 µm in pore size) were implanted into mice pouches, then inoculated with S. aureus at the amounts of 1X10³ CFU and 1X10⁶ CFU per pouch, respectively. Mice were randomized into 4 groups (n=6 for each group): (1) no bacteria; (2) bacteria without saline wash; 3) saline wash only, and (4) saline wash+PVA-VAN/TOB-P. After seven days, pouches were washed out alone or with additional injection of 0.2 ml of PVA-VAN/TOB-P. Mice were sacrificed 14 days after pouch wash. Bacteria cultures of collected Ti cylinders and washout fluid and histology of pouch tissues were performed.

The low-grade infection (1X10³ CFU) was more significant in 400 µm Ti cylinders than that in Ti cylinders with larger pore sizes (700 and 1000 µm (p<0.05). A similar pattern of high-grade infection (1X10⁶ CFU) was observed (p<0.05). For the end wash, the bacteria burden (0.49±0.02) in saline wash group was completely eradicated by the addition of PVA-VAN/TOB-P (0.005±0.001, p<0.05).

We noticed that 400 µm Ti cylinders have the highest risk of implant infection. Our data supported that the effect of saline irrigation was very limited in the presence of contaminated porous Ti cylinders. PVA-VAN/TOB-P was biodegradable, biocompatible, and was effective in eradicating bacteria retention after saline irrigation in a mouse model of low grade and high-grade infection. We believe that PVA-VAN/TOB-P represents an alternative to reduce the risk of PJI by providing a sustained local delivery of antibiotics.

In the field of hand surgery, physicians are working to improve patient satisfaction by offering several minor procedures in the physician's office via the WALANT method. We seek to investigate the degree of patient satisfaction, out of pocket cost, convenience and comfort experienced with in-office hand procedures.

A ten question survey consisting of a ten-point Likert scale of agreement and questions asking for a numerical answer was administered via phone call to 33 patients treated with minor hand operations in the office setting in the United States.

There were 18 male and 15 female respondents with an average age of 65.59±12.64 years. Respondents underwent procedures including trigger finger release (18), needle aponeurotomy (7), and other minor hand operations. Survey responses indicated strong agreement with questions 1-3 and 6–8, with responses averaging 9.60±0.23 in these positive metrics. Questions 4 and 5, which asked whether the surgery and recovery period were painful, respectively, averaged 2.65±0.49, indicating a mild level of disagreement that either was “painful”. Additionally, most patients responded that they did not take time off work (12) or are not currently employed (11). Other respondents (3) reported taking between one to five days off work post-operatively. 27 respondents also reported an out of pocket cost averaging $382±$976, depending on insurance coverage.

Patients reported a small degree of pain in the operative and post-operative period, a high degree of comfort and convenience and a high degree of satisfaction. Likewise, the patient-reported out of pocket cost was far lower than comparable surgical costs in alternate settings. These results support the use of in-office procedures for minor hand surgeries from a patient perspective and indicate a nearly universal intent to repeat any future hand operations in the office setting.

Staphylococcus aureus (SA), the predominant pathogen in human osteomyelitis, is known to persist by forming intracellular reservoirs, including in bone cells (Schwarz et al., 2019, Yang et al., 2018, Krauss et al., 2019, Gao et al., 2020, Bosse et al., 2005), promoting decreased antibiotic susceptibility. However, there are no evidence-based treatment guidelines for intracellular SA infections in osteomyelitis. We sought to address this by systematically reviewing the literature and, testing a selection of antibiotic treatments in a clinically relevant in vitro assay.

We conducted a systematic review of the literature to determine the current evidence for the efficacy of antibiotics against intracellular SA infections relevant to osteomyelitis. For the antibiotics identified as potentially useful, we determined their minimal inhibitory concentration (MIC) against 11 clinical osteomyelitis SA- isolates. We selected those for further testing reported able to reach a higher concentration in the bone than the identified MIC against the majority of strains. Thus, rifampicin, oxacillin, linezolid, levofloxacin, oritavancin and doxycycline were tested in human SaOS-2-osteocyte infection models (Gunn et al., 2021) of acute (1d) or chronic (14d) infection to clear intracellular SA. Antibiotics were tested at 1x/4x/10x the MIC for the duration of 1d or 7d in each model.

A systematic review found that osteoblasts and macrophages have mostly been used to test immediate short-term activity against intracellular SA, with a high variability in methodology. However, some extant evidence supports that rifampicin, oritravancin, linezolid, moxifloxacin and oxacillin may be effective intracellular treatments. While studies are ongoing, in vitro testing in a clinically relevant model suggests that rifampicin, oxacillin and doxycycline could be effectively used to treat osteomyelitic intracellular SA infections. Importantly, these have lower MICs against multiple clinical isolates than their respective clinically-achievable bone concentrations.

The combined approach of a systematic review and disease-relevant in vitro screening will potentially inform as to the best approach for treating osteomyelitis where intracellular SA infection is confirmed or suspected.

Tibial shaft fractures require surgical stabilization preferably by intramedullary nailing. However, patients often report functional limitations even years after the injury. This study investigates the influence of the surgical approach (transpatellar vs. parapatellar) on gait performance and patient reported outcome six months after surgery.

Twenty-two patients with tibial shaft fractures treated by intramedullary nailing through a transpatellar approach (TP: n=15, age 41±15, BMI 24±3) or a parapatellar approach (PP: n=7, age 34±15, BMI 23±2) and healthy, matched controls (n=22, age 39±13, BMI 24±2) were assessed by instrumented motion analysis six months after intramedullary nailing. Short musculoskeletal function assessment questionnaire (SMFA) as well as kinematic and kinetic gait data were collected during level walking. Comparisons among approach methods and control group were performed by analysis of variance and Mann-Whitney test.

Six months after surgery, knee kinetics in both groups differed significantly compared to controls (p <.04). The approach method affected gait speed (TP: p = .002; PP: p = .08) and knee kinematics in the early stance phase (TP: p = .011; PP: p = .082), with the parapatellar approach showing a more favorable outcome. However, the difference between patient groups was not significant for any of the assessed gait parameters (p > .2). Also, no differences could be found in the bother index (BI) or function index (FI) of SMFA between surgical approach methods (BI: TP: Mdn = 7.2, PP: Mdn = 9.4; FI: TP: Mdn = 10.3, PP: Mdn = 9.2, p > .7).

Our study demonstrates, that six months after surgery for tibial shaft fractures functional limitations remain. These limitations appear not to be different for either a trans- or a parapatellar approach for the insertion of the intramedullary nail. The findings of this study are limited by the relatively short follow up time period and small number of patients. Future studies should investigate the source of the functional limitation after intramedullary nailing of tibial shaft fractures.

To test and evaluate the effectiveness of local injection of autologous fat-derived mesenchymal stem cells (MSCs) into fracture site to prevent non-union in a clinically relevant model.

5 male Wistar rats underwent the same surgical procedure of inducing non-union. A mid-shaft tibial osteotomy was made with 1mm non-critical gap. Periosteum was stripped around the two fracture ends. Then, the fracture was fixed by ante-grade intramedullary nail. The non-critical gap was maintained by a spacer with minimal effect on the healing surface area. At the same surgical time, subcutaneous fat was collected from the ipsilateral inguinal region and stem cells were isolated and cultured in vitro. Within three weeks postoperatively, the number of expanded stem cells reached 5×10⁶ and were injected into the fracture site. Healing was followed up for 8 weeks and the quality was measured by serial x-rays, microCT, mechanical testing and histologically. Quality of healing was compared with that of previously published allogenic, xenogeneic MSCs and Purified Buffered Saline (PBS) controls.

All the five fractures united fully after 8 weeks. There was a progressive increase in the callus radiopacity during the eight-week duration, the average radiopacity in the autologous fat-MSC injected group was significantly higher than that of the allogeneic MSCs, xenogeneic MSCs and the control group, P < 0.0001 for treatment, time after injection, and treatment-time interaction (two-way repeated measure ANOVA). MicroCT, mechanical testing and histology confirmed radiological findings.

The autologous fat-MSCs are effective in prevention of atrophic non-union by stimulation of the healing process leading to a solid union. The quality and speed of repair are higher than those of the other types of cell transplantation tested.

Re-rupture rates after rotator cuff repair remain high because of inadequate biological healing at the tendon-bone interface. Single-growth factor therapies to augment healing at the enthesis have so far yielded inconsistent results. An emerging approach is to combine multiple growth factors over a spatiotemporal distribution that mimics normal healing. We propose a novel combination treatment of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1) and parathyroid hormone (PTH) incorporated into a controlled-release tyraminated poly-vinyl-alcohol hydrogel to improve healing after rotator cuff repair. We aimed to evaluate this growth factor treatment in a rat chronic rotator cuff tear model.

A total of 30 male Sprague-Dawley rats underwent unilateral supraspinatus tenotomy. Delayed rotator cuff repairs were then performed after 3 weeks, to allow tendon degeneration that resembles the human clinical scenario. Animals were randomly assigned to: [1] a control group with repair alone; or [2] a treatment group in which the hydrogel was applied at the repair site. All animals were euthanized 12 weeks after rotator cuff surgery and the explanted shoulders were analyzed for biomechanical strength and histological quality of healing at the repair site.

In the treatment group had significantly higher stress at failure (73% improvement, P=0.003) and Young's modulus (56% improvement, P=0.028) compared to the control group. Histological assessment revealed improved healing with significantly higher overall histological scores (10.1 of 15 vs 6.55 of 15, P=0.032), and lower inflammation and vascularity.

This novel combination growth factor treatment improved the quality of healing and strength of the repaired enthesis in a chronic rotator cuff tear model. Further optimization and tailoring of the growth factors hydrogel is required prior to consideration for clinical use in the treatment of rotator cuff tears. This novel treatment approach holds promise for improving biological healing of this clinically challenging problem.

The lateral wall thickness (LWT) in trochanteric femoral fractures is a known predictive factor for postoperative fracture stability. Currently, the AO/OTA classification uses a patient non-specific measure to assess the absolute LWT (aLWT) and distinguish stable A1.3 from unstable A2.1 fractures based on a threshold of 20.5 mm. This approach potentially results in interpatient deviations due to different bone morphologies and consequently variations in fracture stability. Therefore, the aim of this study was to explore whether a patient-specific measure for assessment of the relative LWT (rLWT) results in a more precise threshold for prediction of unstable fractures.

Part 1 of the study evaluated 146 pelvic radiographs to assess left-right symmetry with regard to caput-collum-angle (CCD) and total trochanteric thickness (TTT), and used the results to establish the rLWT measurement technique. Part 2 reevaluated 202 patients from a previous study cohort to analyze their rLWT versus aLWT for optimization purposes.

Findings in Part 1 demonstrated a bilateral symmetry of the femur regarding both CCD and TTT (p ≥ 0.827) allowing to mirror bone's morphology and geometry from the contralateral intact to the fractured femur. Outcomes in Part 2 resulted in an increased accuracy for the new determined rLWT threshold (50.5%) versus the standard 20.5 mm aLWT threshold, with sensitivity of 83.7% versus 82.7% and specificity 81.3% versus 77.8%, respectively.

The novel patient-specific rLWT measure can be based on the contralateral femur anatomy and is a more accurate predictor of a secondary lateral wall fracture in comparison to the conventional aLWT. This study established the threshold of 50.5% rLWT as a reference value for prediction of fracture stability and selection of an appropriate implant for fixation of trochanteric femoral fractures.

To analyse bone stresses in humerus-megaprosthesis construct in response to axial loading under varying implant lengths in proximal humeral replacement following tumour excision.

CT scans of 10 cadaveric humeri were processed in 3D Slicer to obtain three-dimensional (3D) models of the cortical and cancellous bone. Megaprostheses of varying body lengths (L) were modelled in FreeCAD to obtain the 3D geometry. Four FE models: group A consisting of intact bone; groups B (L=40mm), C (L=100mm) and D (L=120mm) comprising of humerus-megaprosthesis constructs were created. Isotropic linear elastic behaviour was assigned for all materials. A tensile load of 200N was applied to the elbow joint surface with the glenohumeral joint fixed with fully bonded contact interfaces. Static analysis was performed in Abaqus. The bone was divided at every 5% bone length beginning distally. Statistical analysis was performed on maximum von Mises stresses in cortical and cancellous bone across each slice using one-way ANOVA (0-45% bone length) and paired t-tests (45-70% bone length). To quantify extent of stress shielding, average percentage change in stress from intact bone was also computed.

Maximum stress was seen to occur distally and anteriorly above the coronoid fossa. Results indicated statistically significant differences between intact state and shorter megaprostheses relative to longer megaprostheses and proximally between intact and implanted bones. Varying levels of stress shielding were recorded across multiple slices for all megaprosthesis lengths. The degree of stress shielding increased with implant lengthening being 2-4 times in C and D compared to B.

Axial loading of the humerus can occur with direct loading on outstretched upper limbs or indirectly through the elbow. Resultant stress shielding effect predicted in longer megaprosthesis models may become clinically relevant in repetitive axial loading during activities of daily living. It is recommended to use shorter megaprosthesis to prevent failure.

The e-scooter trial was part of a wider initiative from the Department for Transport in response to COVID pandemic. New emergency legislation was introduced in 2020 to make e-scooters legal in the UK for the first time. This scheme was launched in our county from September 2020. The aim of this case series was to identify the types of Orthopedic injuries resultant from electric scooter transport that presented to our District General Hospital over a 16-month period between September 2020 and December 2021.

This study involved retrospective collection of data from electronic hospital records. Data on demographics, laterality, date of injury, type of injury, treatment, HDU/ITU admissions, mortality, and operating time were collected to characterize the types of e-scooter-related injuries and to investigate the frequency of such injuries over the duration of our search.

A total of 79 orthopedic patients identified with electric scooter injuries between September 2020 and December 2021. 78.5% were males and the mean age was 30.1 years. Summer months accounted for most of the injuries. 17 patients required inpatient care. 23 patients required surgical intervention and a total of 29 surgeries were performed in our hospital. This accounted for a total surgical time of 2088 minutes. One patient admitted with shaft of femur fracture developed pulmonary embolism after the definitive operation and died in HDU.

Electric scooters provide a space efficient, affordable, environmentally friendly mode of transportation which reduce the urban congestion and parking issues. This study demonstrates an increasing frequency of significant orthopedic injury associated with e-scooter use treated at our centre over the course of 16 months. This small series underlines an important problem given that this increase has occurred after the start of the electric scooter trial. Legalization might result in further increase in the incidence of injury.

This study aims to compare the biomechanical properties of the “Double Lasso-Loop” suture anchor (DLSA) technique with the commonly performed interference screw (IS) technique in an ex vivo ovine model.

Fourteen fresh sheep shoulder specimens were used in this study. Dissection was performed leaving only the biceps muscle attached to the humerus and proximal radius before sharply incised to simulate long head of biceps tendon (LHBT) tear. Repair of the LHBT tear was performed on all specimens using either DSLA or IS technique. Cyclical loading of 500 cycles followed by load to failure was performed on all specimens. Tendon displacement due to the cyclical loading at every 100 cycles as well as the maximum load at failure were recorded and analysed. Stiffness was also calculated from the load displacement graph during load to failure testing.

No statistically significant difference in tendon displacement was observed from 200 to 500 cycles. Statistically significant higher stiffness was observed in IS when compared with DSLA (P = .005). Similarly, IS demonstrated significantly higher ultimate failure load as compared with DSLA (P = .001). Modes of failure observed for DSLA was mostly due to suture failure (7/8) and anchor pull-out (1/8) while IS resulted in mostly LHBT (4/6) or biceps (2/6) tears. DSLA failure load were compared with previous studies and similar results were noted.

After cyclical loading, tendon displacement in DLSA technique was not significantly different from IS technique. Despite the higher failure loads associated with IS techniques in the present study, absolute peak load characteristics of DLSA were similar to previous studies. Hence, DLSA technique can be considered as a suitable alternative to IS fixation for biceps tenodesis.

Bone defects require implantable graft substitutes, especially porous and biodegradable biomaterial for tissue regeneration. The aim of this study was to fabricate and assess a 3D-printed biodegradable hydroxyapatite/calcium carbonate scaffold for bone regeneration.

Depletion of Scleraxis-lineage (ScxLin) cells in adult tendon recapitulates age-related decrements in cell density, ECM organization and composition. However, depletion of ScxLin cells improves tendon healing, relative to age-matched wildtype mice, while aging impairs healing. Therefore, we examined whether ScxLin depletion and aging result in comparable shifts in the tendon cell environment and defined the intrinsic programmatic shifts that occur with natural aging, to define the key regulators of age-related healing deficits.

ScxLin cells were depleted in 3M-old Scx-Cre+; Rosa-DTRF/+ mice via diphtheria toxin injections into the hindpaw. Rosa-DTRF/+ mice were used as wildtype (WT) controls. Tendons were harvested from 6M-old ScxLin depleted and WT mice, and 21-month-old (21M) C57Bl/6 mice (aged). FDL tendons (n=6) were harvested for single-cell RNAseq, pooled, collagenase digested, and sorted for single cell capture. Data was processed using Cell Ranger and then aligned to the annotated mouse genome (mm10). Filtering, unsupervised cell clustering, and differential gene expression (DEG) analysis were performed using Seurat.

Following integration and sub-clustering of the tenocyte populations, five distinct subpopulations were observed. In both ScxLin depletion and aging, ‘ECM synthesizers’ and ‘ECM organizers’ populations were lost, consistent with disruptions in tissue homeostasis and altered ECM composition. However, in ScxLin depleted mice retention of a ‘specialized ECM remodeler’ population was observed, while aging tendon cells demonstrated inflammatory skewing with retention of a ‘pro-inflammatory tenocyte population’. In addition, enrichment of genes associated with protein misfolding clearance were observed in aged tenocytes. Finally, a similar inflammatory skewing was observed in aged tendon-resident macrophages, with this skewing not observed in ScxLin depleted tendons.

These data suggest that loss of ‘ECM synthesizer’ populations underpins disruptions in tendon homeostasis. However, retention of ‘specialized remodelers’ promotes enhanced healing (ScxLin depletion), while inflammatory skewing may drive the impaired healing response in aged tendons.

3D spheroid culture is a bridge between standard 2D cell culture and in vivo research which mimics the physiological microenvironment in scaffold-free conditions. Here, this 3D technique is being investigated as a potential method for engineering bone tissue in vitro. However, spheroid culture can exhibit limitations, such as necrotic core formation due to the restricted access of oxygen and nutrients. It is therefore important to determine if spheroids without a sizeable necrotic core can be produced. This study aims to understand necrotic core formation and cell viability in 3D bone cell spheroids using different seeding densities and media formulations.

Differentiated rat osteoblasts (dRObs) were seeded in three different seeding densities (1×10⁴, 5×10⁴, 1×10 cells) in 96 well U-bottom cell-repellent plates and in three different media i.e., Growth medium (GM), Mineralisation medium 1 (MM1) and MM2. Spheroids were analysed from day 1 to 28 (N=3, n=2). Cell count and viability was assessed by trypan blue method. One way ANOVA and post-hoc Tukey test was performed to compare cell viability among different media and seeding densities. Histological spheroid sections were stained with hematoxylin and eosin (H&E) to identify any visible necrotic core.

Cell number increased from day 1 to 28 in all three seeding densities with a notable decrease in cell viability. 1×10⁴ cells proliferated faster than 5×10⁴ and 1×10⁵ cells and had proportionately similar cell death. The necrotic core area was relatively equivalent between all cell seeding densities. The larger the spheroid size, the larger is the size of the necrotic core.

This study has demonstrated that 3D spheroids can be formed from dRobs at a variety of seeding densities with no marked difference in necrotic core formation. Future studies will focus on utilising the bone cell spheroids for engineering scalable scaffold-free bone tissue constructs.

Helical plates potentially bypass the medial neurovascular structures of the thigh. Recently, two plate designs (90°- and 180°-helix) proved similar biomechanically behaviour compared to straight plates. Aims of this study were: (1) Feasibility of MIPO-technique with 90°- and 180°-helical plates on the femur, (2) Assessment of distances to adjacent anatomical structures at risk, (3) Comparison of these distances to using medial straight plates instead, (4) Correlation of measurements performed in anatomic dissection with CT-angiography.

MIPO was performed in ten cadaveric femoral pairs using either a 90°-helical 14-hole-LCP (Group1) or a 180°-helical 15-hole-LCP-DF (Group2). CT angiography was used to evaluate the distances between the plates and the femoral arteries as well as the distances between the plates and the perforators. Subsequently, the specimens were dissected, and the distances were determined again manually. Finally, all helical plates were removed, and all measurements were repeated after application of straight medial plates (Group3).

Closest overall distances between plates and femoral arteries were 15 mm (11 − 19 mm) in Group1, 22 mm (15 − 24 mm) in Group2 and 6 mm (1 − 8 mm) in Group3 with a significant difference between Group1 and Group3 (p < 0.001). Distances to the nearest perforators were 24 mm (15 − 32 mm) in Group1 and 2 mm (1 − 4 mm) in Group2. Measurement techniques (visual after surgery and CT-angiography) demonstrated a strong correlation of r² = 0.972 (p < 0.01).

MIPO with 90°- and 180°-helical plates is feasible and safe. Attention must be paid to the medial neurovascular structures with 90°-helical implants and to the proximal perforators with 180°-helical implants. Helical implants can avoid medial neurovascular structures compared to straight plates although care must be taken during their distal insertion. Measurements during anatomical dissection correlate with CT-angiography.

Primary malignant bone and soft tissue tumours often occur in the lower extremities of active individuals including children, teenagers and young adults. Survivors routinely face long-term physical disability. Participation in sports is particularly important for active young people but the impact of sarcoma treatment is not widely recognised and clinicians may be unable to provide objective advice about returning to sports. We aimed to identify and summarise the current evidence for involvement in sports following treatment of lower limb primary malignant bone and soft tissue tumours.

A comprehensive search strategy was used to identify relevant studies combining the main concepts of interest: (1) Bone/Soft Tissue Tumour, (2) Lower Limb, (3) Surgical Interventions and (4) Sports. Studies were selected according to eligibility criteria with the consensus of three authors. Customised data extraction and quality assessment tools were used.

22 studies were selected, published between 1985 – 2020, and comprising 1005 patients. Fifteen studies with data on return to sports including 705 participants of which 412 (58.4%) returned to some form of sport at a mean follow-up period of 7.6 years. Four studies directly compared limb sparing and amputation; none of these were able to identify a difference in sports participation or ability.

Return to sports is important for patients treated for musculoskeletal tumours, however, there is insufficient published research to provide good information and support for patients. Future prospective studies are needed to collect better pre and post-treatment data at multiple time intervals and validated clinical and patient sports participation outcomes such as type of sports participation, level and frequency and a validated sports specific outcome score, such as UCLA assessment. In particular, more comparison between limb sparing and amputation would be welcome.

For patients who took joint replacement, one of the complications, aseptic joint loosening, could cause a high risk of revision surgery. Studies have shown that MSCs have the ability of homing and differentiating, and also have highly effective immune regulation and anti-inflammatory effects. However, few studies had focused on the stem cells in preventing the occurrence and development of aseptic loosening. In this research, we aimed to clarify whether human umbilical cord mesenchymal stem cells could inhibited the aseptic joint loosening caused by wear particles.

A Cranial osteolysis mice model was established on mice to examine the effect of hUC-MSCs on the Titanium particles injection area through micro-CT. The amount of stem cells injected was 2 × 10 5 cells. One week later, the mouse Cranial were obtained for micro-CT scan, and then stained with HE analysis immunohistochemical analysis of TNF-α, CD68, CCL3 and Il-1β.

All mice were free of fever and other adverse reactions, and there was no death occurred. Titanium particles caused the osteolysis at the mice cranial, while local injection of hUC-MSCs did inhibit the cranial osteolysis, with a lower BV/TV and a higher porosity. Immunohistochemical results suggested that the expression of TNF-α, CD68, CCL3 and Il-1β in the cranial in Titanium particles mice increased significantly, but was significantly reduced in mice injected with hUC-MSCs. The inhibited CD68 expression indicated that the number of macrophage was lower, which might be a result of the inhibition of CCL3.

According to the studies above, HUC-MSCs treatment of mouse cranial osteolysis model can significantly reduce osteolysis, inhibit macrophage recruitment, alleviate inflammatory response, without causing adverse reactions. It may become a promising treatment of aseptic joint loosening.

The current study aims to compare the clinico radiological outcomes between Non-Fusion Anterior Scoliosis (NFASC) Correction and Posterior Spinal Fusion (PSF) for Lenke 5 curves at 2 years follow up.

Methods:38 consecutive Lenke 5 AIS patients treated by a single surgeon with NFASC (group A) or PSF (group B) were matched by age, Cobb's angle, and skeletal maturity. Intraoperative blood loss, operative time, LOS, coronal Cobbs, and SRS22 scores at 2 years were compared. Flexibility was assessed by modified Schober's test. Continuous variables were compared using student t-tests and categorical variables were compared using chi-square.

The cohort included 19 patients each in group A and B . Group A had M:F distribution of 1:18 while group B had 2:17. The mean age in group A and group B were 14.8±2.9 and 15.3±3.1 years respectively. The mean follow-up of patients in groups A and B were 24.5±1.8 months and 27.4±2.1 months respectively. Mean pre-op thoracolumbar/lumbar (TL/L) cobbs for group A and group B were 55°±7° and 57.5°±8° respectively. At two years follow up, the cobbs for group A and B were 18.2°±3.6° and 17.6°±3.5° respectively (p=0.09). The average operating time for groups A and B were 169±14.2 mins and 219±20.5 mins respectively (p<0.05). The average blood loss of groups A and B were 105.3±15.4 and 325.3±120.4 respectively (p<0.05). The average number of instrumented vertebra between groups A and B were 6.2 and 8.5 respectively (p<0.05). The average LOS for NFASC and PSF was 3.3±0.9 days and 4.3±1.1 days respectively (p<0.05). No statistically significant difference in SRS 22 score was noted between the two groups. No complications were recorded.

Our study shows no significant difference in PSF and NFASC in terms of Cobbs correction and SRS scores, but the NFASC group had significantly reduced blood loss, operative time, and fewer instrumented levels. NFASC is an effective alternative technique to fusion to correct and stabilize Lenke 5 AIS curves with preservation of spinal motion.

Treatment of simple and complex patella fractures represents a challenging clinical problem. Controversy exists regarding the most appropriate fixation method. Tension band wiring, aiming to convert the pulling forces on the anterior aspect of the patella into compression forces across the fracture site, is the standard of care, however, it is associated with high complication rates. Recently, anterior variable-angle locking plates have been developed for treatment of simple and comminuted patella fractures. The aim of this study was to investigate the biomechanical performance of the novel anterior variable-angle locking plates versus tension band wiring used for fixation of simple and complex patella fractures.

Sixteen pairs of human cadaveric knees were used to simulate either two-part transverse simple AO/OTA 34-C1 or five-part complex AO/OTA 34-C3 patella fractures by means of osteotomies, with each fracture model created in eight pairs. The complex fracture pattern was characterized with a medial and a lateral proximal fragment, together with an inferomedial, an inferolateral and an inferior fragment mimicking comminution around the distal patellar pole. The specimens with simple fractures were pairwise assigned for fixation with either tension band wiring through two parallel cannulated screws, or an anterior variable-angle locking core plate. The knees with complex fractures were pairwise treated with either tension band wiring through two parallel cannulated screws plus circumferential cerclage wiring, or an anterior variable-angle locking three-hole plate. Each specimen was tested over 5000 cycles by pulling on the quadriceps tendon, simulating active knee extension and passive knee flexion within the range from 90° flexion to full knee extension. Interfragmentary movements were captured by motion tracking.

For both fracture types, the articular displacements, measured between the proximal and distal fragments at the central aspect of the patella between 1000 and 5000 cycles, together with the relative rotations of these fragments around the mediolateral axis were all significantly smaller following the anterior variable-angle locked plating compared with the tension band wiring, p < 0.01

From a biomechanical perspective, anterior locked plating of both simple and complex patella fractures provides superior construct stability versus tension band wiring.

Though dentin matrix protein 1 (Dmp1) is known to play critical role in mediating bone mineralization, it has also been validated to be expressed in brain and helps maintain blood brain barrier (BBB). Our study aims to clarify the expression pattern of Dmp1 in mouse brain and explore whether intercellular mitochondrial transfer occurs between Dmp1 positive astrocytes (DPAs) and endothelial cells, and thus acting as a mechanism in maintaining BBB during aging.

Single cell RNA sequencing (scRNAseq) of 1 month, 6 month, and 20 month old mice brain (n=1, respectively) was employed to identify Dmp1 positive cell types. Dmp1^Cre-mGmT and Dmp1^Cre-COX8a fluorescent mice were generated to visualize DPAs and investigate their mitochondrial activities. A 3D noncontact coculture system and mitochondrial transplantation were applied to study the role of mitochondrial transfer between astrocytes and bEnd.3 endothelial cells. Dmp1^Cre-Mfn2^f/f mice were generated by depleting the ER-mitochondria tethering protein Mfn2 in DPAs.

Dmp1 was mainly expressed in astrocytes at different ages. GO analysis revealed that cell projection and adhesion of DPAs were upregulated. Confocal imaging on Dmp1^Cre-mGmT mice indicated that DPAs are a cluster of astrocytes that closely adhere to blood vessels (n=3). Bioinformatics analysis revealed that mitochondrial activity of DPAs were compromised during aging. Enriched scRNAseq of fluorescent cells from Dmp1^Cre-COX8a mice (n=2) and immunofluorescent imaging (n=3) validated the acquisition of extrinsic mitochondria in endothelial cells. 3D coculture of astrocytes and bEnd.3 and direct mitochondrial transplantation revealed the rescue effect of mitochondrial transfer on damaged bEnd.3. BBB was impaired after depleting Mfn2 in DPAs, expressing a similar phenotype with aging brain.

Astrocytes that express Dmp1 play a significant role in maintaining BBB via transferring mitochondria to vascular endothelial cells. Compromised mitochondrial transfer between DPAs and endothelial cells might be the potential mechanism of impaired BBB during aging.

Intervertebral disc degeneration can lead to physical disability and significant pain, while the present therapeutics still fail to biochemically and biomechanically restore the tissue. Stem cell-based therapy in treating intervertebral disc (IVD) degeneration is promising while transplanting cells alone might not be adequate for effective regeneration. Recently, gene modification and 3D-printing strategies represent promising strategies to enhanced therapeutic efficacy of MSC therapy. In this regard, we hypothesized that the combination of thermosensitive chitosan hydrogel and adipose derived stem cells (ADSCs) engineered with modRNA encoding Interleukin − 4 (IL-4) can inhibit inflammation and promote the regeneration of the degenerative IVD.

Rat ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IL-4 modRNA engineered ADSCs (named as IL-4-ADSCs) on nucleus pulposus cells.

ModRNA transfected mouse ADSCs with high efficiency and the IL-4 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IL-4 protein. In vitro, IL-4-ADSCs induced increased anabolic markers expression of nucleus pulposus cells in inflammation environment compared to untreated ADSCs.

These findings collectively supported the therapeutic potential of the combination of thermosensitive chitosan hydrogel and IL-4-ADSCs for intervertebral disc degeneration management. Histological and in vivo validation are now being conducted.

There is controversy regarding the effect of different approaches on recovery after THR. Collecting detailed relevant data with satisfactory compliance is difficult. Our retrospective observational multi-center study aimed to find out if the data collected via a remote coaching app can be used to monitor the speed of recovery after THR using the anterolateral (ALA), posterior (PA) and the direct anterior approach (DAA).

771 patients undergoing THR from 13 centers using the moveUP platform were identified. 239 had ALA, 345 DAA and 42 PA. There was no significant difference between the groups in the sex of patients or in preoperative HOOS Scores. There was however a significantly lower age in the DAA (64,1y) compared to ALA (66,9y), and a significantly lower Oxford Hip Score in the DAA (23,9) compared to PA(27,7). Step count measured by an activity tracker, pain killer and NSAID use was monitored via the app. We recorded when patients started driving following surgery, stopped using crutches, and their HOOS and Oxford hip scores at 6 weeks.

Overall compliance with data request was 80%. Patients achieved their preoperative activity level after 25.8, 17,7 and 23.3 days, started driving a car after 33.6, 30.3 and 31.7 days, stopped painkillers after 27.5, 20.2 and 22.5 days, NSAID after 30.3, 25.7, and 24.7 days for ALA, DAA and PA respectively. Painkillers were stopped and preoperative activity levels were achieved significantly earlier favoring DAA over ALA. Similarly, crutches were abandoned significantly earlier (39.9, 29.7 and 24.4 days for ALA, DAA and PA respectively) favoring DAA and PA over ALA. HOOS scores and Oxford Hip scores improved significantly in all 3 groups at 6 weeks, without any statistically significant difference between groups in either Oxford Hip or HOOS subscores.

No final conclusion can be drawn as to the superiority of either approach in this study but the remote coaching platform allowed the collection of detailed data which can be used to advise patients individually, manage expectations, improve outcomes and identify areas for further research.

An international Consensus Group has by a Delphi approach identified the topic of host factors affecting pin site infection to be one of the top 10 priorities in external fixator management. The aim of this study was to report the frequency of studies reporting on specific host factors as a significant association with pin site infection. Host factors to be assessed was: age, smoking, BMI and any comorbidity, diabetes, in particular. The intention was an ethological review, data was extracted if feasible, however no meta-analysis was performed.

A systematic literature search was performed according to the PRISMA-guidelines. The protocol was registered before data extraction in PROSPERO. The search string was based on the PICO criterias. A logic grid with key concept and index terms was made. A search string was built assisted by a librarian. The literature search was executed in three electronic bibliographic databases, including Embase MEDLINE (1111 hits) and CINAHL (2066 hits) via Ovid and Cochrane Library CENTRAL (387 hits). Inclusion criteria: external fixation, >1 pin site infection, host factor of interest, peer-reviewed journal. Exclusion criteria: Not written in English, German, Danish, Swedish, or Norwegian, animal or cadaveric studies, location on head, neck, spine, cranium or thorax, editorials or conference abstract. The screening process was done using Covidence.

A total of 3564 titles found. 3162 excluded by title and abstract screening. 140 assessed for full text eligibility. 11 studies included for data extraction. The included studies all had a retrospective design. Three identified as case-control studies. Generally the included studies was assessed to have a high risk of bias. A significant associations between pin site infection for following host factors: a) increased HbA1C level in diabetic patients; b) congestive heart failure in diabetic patients; c) less co-morbidity; d) preoperative osteomyelitis was found individually.

This systematic literature search identified a surprisingly low number of studies examining for risk of pin site infection and host factors. Thus, this review most of all serves to demonstrate a gap of evidence about correlation between host factors and risk of pin site infection, and further studies are warranted.

Fragility ankle fractures are traditionally managed conservatively or with open reduction internal fixation (ORIF). Tibiotalocalcaneal (TTC) fusion is an alternative option for the geriatric patient. This systematic review and meta-analysis provides a detailed analysis of the functional and clinical outcomes of hindfoot nailing for fragility ankle fractures presented so far in the literature.

A systematic search was performed on MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science, identifying fourteen studies for inclusion. Studies including patients over 60 with a fragility ankle fracture, treated with TTC nail were included. Patients with a previous fracture of the ipsilateral limb, fibular nails, and pathological fractures were excluded.

Subgroup analyses were performed according to (1) open vs closed fractures, (2) immediate post-operative FWB vs post-operative NWB, (3) majority of cohort are diabetics vs minority of cohort are diabetics. Meta-regression analyses were done to explore sources of heterogeneity, and publication bias was assessed using Egger's test.

The pooled proportion of superficial infection, deep infection, implant failure, malunion, and all-cause mortality was 0.10 (95%CI:0.06-0.16; I2=44%), 0.08 (95%CI:0.06-0.11, I2=0%), 0.11 (95%CI:0.07-0.15, I2=0%), 0.11 (95%CI:0.06-0.18; I2=51%), and 0.27 (95%CI:0.20-0.34; I2=11%), respectively. The pooled mean post-operative OMAS score was 54.07 (95%CI:48.98-59.16; I2=85%). The best-fitting meta-regression model included age and percentage of male patients as covariates (p=0.0263), and were inversely correlated with higher OMAS scores.

Subgroup analyses showed that studies with a majority of diabetics had a higher proportion of implant failure (p=0.0340) and surgical infection (p=0.0096), and a lower chance of returning to pre-injury mobility than studies with a minority of diabetics (p=0.0385). Egger's test (p=0.56) showed no significant publication bias.

TTC nailing is an adequate alternative option for fragility ankle fractures. However, current evidence includes mainly case series with inconsistent outcome measures reported and post-operative rehabilitation protocols. Prospective RCTs with long follow-up times and large cohort sizes are needed to clearly guide the use of TTC nailing for ankle fractures.

Nerve transfer is an emerging treatment to restore upper limb function in people with tetraplegia. The objective of this study is to examine if a flexible collage sheet (FCS) can act as epineurial-like substitute to promote nerve repair in nerve transfer.

A preclinical study using FCS was conducted in a rat model of sciatic nerve transection. A prospective case series study of nerve transfer was conducted in patients with C5-C8 tetraplegia who received nerve transfer to restore upper limb function. Motor function in the upper limb was assessed pre-treatment, and at 6-,12-, and 24-months post-treatment.

Macroscopic assessment in preclinical model showed nerve healing by FCS without encapsulation or adhesions. Microscopic examination revealed that a new, vascularised epineurium-like layer was observed at the FCS treatment sites, with no evidence of inflammatory reaction or nerve compression. Treatment with FCS resulted in well-organised nerve fibres with dense neurofilaments distal to the coaptation site. Axon counts performed proximal and distal to the coaptation site showed that 97% of proximal axon count of myelinated axons regenerated across the coaptation site after treatment with CND. In the proof of concept clinical study 17 nerve transfers were performed in five patients. Nerve transfers included procedures to restore triceps function (N=4), wrist/finger/thumb extension (N=6) and finger flexion (N=7). Functional motor recovery (MRC ≥3) was achieved in 76% and 88% of transfers at 12 and 24 months, respectively.

The preclinical study showed that FCS mimics epineurium and enable to repair nerve resembled to normal nerve tissue. Clinical study showed that patients received nerve transfer with FCS experienced consistent and early return of motor function in target muscles. These results provide proof of concept evidence that CND functions as an epineurial substitute and is promising for use in nerve transfer surgery.

Arthroscopic management of femoroacetabular impingement (FAI) has become the mainstay of treatment. However, chondral lesions are frequently encountered and have become a determinant of less favourable outcomes following arthroscopic intervention.

The aim of this systematic review and meta-analysis was to assess the outcomes of hip arthroscopy (HA) in patients with FAI and concomitant chondral lesions classified as per Outerbridge.

A systematic search was performed using the PRISMA guidelines on four databases including MEDLINE, EMBASE, Cochrane Library and Web of Science. Studies which included HA as the primary intervention for management of FAI and classified chondral lesions according to the Outerbridge classification were included. Patients treated with open procedures, for osteonecrosis, Legg-Calve-Perthes disease, and previous ipsilateral hip fractures were excluded. From a total of 863 articles, twenty-four were included for final analysis. Demographic data, PROMs, and radiological outcomes and rates of conversion to total hip arthroplasty (THA) were collected. Risk of bias was assessed using ROBINS-I.

Improved post-operative PROMs included mHHS (mean difference:-2.42; 95%CI:-2.99 to −1.85; p<0.001), NAHS (mean difference:-1.73; 95%CI: −2.23 to −1.23; p<0.001), VAS (mean difference: 2.03; 95%CI: 0.93-3.13; p<0.001). Pooled rate of revision surgery was 10% (95%CI: 7%-14%). Most of this included conversion to THA, with a 7% pooled rate (95%CI: 4%-11%).

Patients had worse PROMs if they underwent HA with labral debridement (p=0.015), had Outerbridge 3 and 4 lesions (p=0.012), concomitant lesions of the femoral head and acetabulum lesions (p=0.029). Reconstructive cartilage techniques were superior to microfracture (p=0.042). Even in concomitant lesions of the femoral head and acetabulum, employing either microfracture or cartilage repair/reconstruction provided a benefit in PROMs (p=0.027).

Acceptable post-operative outcomes following HA with labral repair/reconstruction and cartilage repair in patients with FAI and concomitant moderate-to-severe chondral lesions, can be achieved. Patients suffering from Outerbridge 3 and 4 lesions, concomitant acetabular rim and femoral head chondral lesions that underwent HA with labral debridement, had worse PROMs. Reconstructive cartilage techniques were superior to microfracture. Even in concomitant acetabular and femoral head chondral lesions, employing either microfracture or cartilage repair/reconstruction was deemed to provide a benefit in PROMs.

Nitric oxide is a free radical which in vivo is solely produced during the conversion of the amino acid arginine into citrulline by nitric oxide synthase enzymes. Recently, the importance of nitric oxide on inflammation and bone metabolism has been investigated. However, the knowledge regarding possible in vitro effects of arginine supplementation on chondrogenic differentiation is limited.

ATDC5, a cell line which is derived from mouse teratocarcinoma cells and which is characterized as chondrogenic cell line, were proliferated in Dulbecco's Modified Eagle Medium (DMEM)/F12 and subsequently differentiated in proliferation medium supplemented with insulin, transferrin and sodium-selenite and where arginine was added in four different concentrations (0, 7.5, 15 and 30 mM). Samples were harvested after 7 or 10 days and were stored at −80 °C for subsequent RNA isolation for qPCR analysis. To determine chondrogenic differentiation, Alcian Blue staining was performed to stain the proteoglycan aggrecan, which is secreted by differentiated ATDC5 cells. All measurements were performed in triplo.

Alcian Blue staining showed a qualitative increase of proteoglycan aggrecan secretion in differentiated ATDC5 cells after treatment with 7 and 15 mM arginine, with additional increased expression of ColII, ColX, Bmp4 and Bmp6. Treatment with 30 mM arginine inhibited chondrogenic differentiation and expression of aforementioned genes, however, Cox-2 and Vegfa gene expression were increased in these samples. Bmp7 was not significantly expressed in any experimental condition.

The obtained results are suggestive for a dose-dependent effect of arginine supplementation on chondrogenic differentiation and associated gene expression, with 7.5 and 15 mM as most optimal concentrations and implications for apoptosis after incubation with 30 mM arginine. A future recommendation would be to investigate the effects of citrulline in a similar experiment, as this shows even more promising results to enhance the nitric oxide metabolism in sepsis and bone healing.

Osteochondromas are benign chondrogenic lesions arising on the external surface of the bone with aberrant cartilage (exostosis) from the perichondral ring that may contain a marrow cavity also. In a few cases, depending on the anatomical site affected, different degrees of edema, redness, paresthesia, or paresis can take place due to simple contact or friction. Also, depending on their closeness to neurovascular structures, the procedure of excision becomes crucial to avoid recurrence. We report a unique case of recurrent osteochondroma of the proximal humerus enclosing the brachial artery which makes for an important case and procedure to ensure that no relapse occurs.

We report a unique case of a 13-year-old female who had presented with a history of pain and recurrent swelling for 5 years. The swelling size was 4.4 cm x 3.7 cm x 4 cm with a previous history of swelling at the same site operated in 2018. CT reports were suggestive of a large well defined broad-based exophytic diaphyseal lesion in the medial side of the proximal humerus extending posteriorly. Another similar morphological lesion measuring approximately 9 mm x 7 mm was noted involving the posterior humeral shaft. The minimal distance between the lesion and the brachial artery was 2 mm just anterior to the posterio-medial growth. Two intervals were made, first between the tumor and the neurovascular bundle and the other between the anterior tumor and brachial artery followed by exostosis and cauterization of the base.

Proper curettage and excision of the tumor was done after dissecting and removing the soft tissue, blood vessels, and nerves so that there were very less chances of relapse. Post-operative X-ray was done and post 6 months of follow-up, there were no changes, and no relapse was observed. Thus, when presented with a case of recurrent osteochondroma of the proximal humerus, osteochondroma could also be in proximity to important vasculature as in this case enclosing the brachial artery. Thus, proper curettage and excision should be done in such cases to avoid recurrence.

Intraoperative fractures although rare are one of the complications known to occur while performing a total hip arthroplasty (THA). However, due to lower incidence rates there is currently a gap in this area of literature that systematically reviews this important issue of complications associated with THA.

Method: We looked into Electronic databases including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), the archives of meetings of orthopaedic associations and the bibliographies of included articles and asked experts to identify prospective studies, published in any language that evaluated intra-operative fractures occurring during total hip arthroplasty from the year 1950-2020. The screening, data extraction and quality assessment were carried out by two researchers and if there was any discrepancy, a third reviewer was involved.

Fourteen studies were identified. The reported range of occurrence of fracture while performing hip replacement surgery was found to be 0.4-7.6%. Major risk factors identified were surgical approaches, Elderly age, less Metaphyseal-Diaphyseal Index score, change in resistance while insertion of the femur implants, inexperienced surgeons, uncemented femoral components, use of monoblock elliptical components, implantation of the acetabular components, patients with ankylosing spondylitis, female gender, uncemented stems in patients with abnormal proximal femoral anatomy and with cortices, different stem designs, heterogeneous fracture patterns and toothed design.

Intraoperative fractures during THA were managed with cerclage wire, femoral revision, intramedullary nail and cerclage wires, use of internal fixation plates and screws for management of intra operative femur and acetabular fractures.

The main reason for intraoperative fracture was found to be usage of cementless implants but planning and timely recognition of risk factors and evaluating them is important in management of intraoperative fractures. Adequate surgical site exposure is critical especially during dislocation of hip, reaming of acetabulum, impaction of implant and preparing the femoral canal for stem insertion. Eccentric and increased reaming of acetabulum to accommodate a larger cup is to be avoided, especially in females and elderly patients as the acetabulum is thinner. However, this area requires more research in order to obtain more evidence on effectiveness, safety and management of intraoperative fractures during THA.

Previous studies showed that telo-peptides degraded from type II collagen, a type of collagen fragments, could induce cartilage damage in bovine stifle joints. We aim to investigate the role of integrins (ITGs) and matrix metalloproteinases (MMPs) in collagen fragment-induced human cartilage damage that is usually observed in osteoarthritis (OA). We hypothesized that N-telopeptide (NT) derived from type II collagen could up-regulate the expression of β1 integrin (ITGB1) and then MMPs that may lead to osteoarthritic cartilage damage.

Human chondrocytes were isolated from femoral head or tibial plateau of patients receiving arthroplasty (N = 24). Primary chondrocyte cultures were either treated with 30 µM NT, or 30 µM scrambled NT (SN), or PBS, or left untreated for 24 hrs. Total proteins and RNAs were extracted for examination of expression of ITGB1 and MMPs-3&13 with Western blotting and quantitative real-time PCR.

Compared to untreated or PBS treated chondrocytes, NT-treated chondrocytes expressed significantly higher levels of ITGB1 and MMPs-3&-13. However, SN also up-regulated expression of ITGB1 and MMP-13.

ITGB1 and MMPs-3&-13 might mediate the catalytic effect of NT, a type of collagen fragments, on human cartilage damage that is a hallmark of OA.

Pelvic tilt can vary over time due to aging and the possible appearance of sagittal spine disorders. Cup position in total hip arthroplasty (THA) can be influenced due to these changes. We assessed the evolution of pelvic tilt and cup position after THA and the possible appearance of complications for a minimum follow-up of ten years.

343 patients received a THA between 2006 and 2009. All were diagnosed with primary osteoarthritis and their mean age was 63.3 years (range, 56 to 80). 168 were women and 175 men. 250 had no significant lumbar pathology, 76 had significant lumbar pathology and 16 had lumbar fusion. Radiological analysis included sacro-femoral-pubic (SFP), acetabular abduction (AA) and anteversion cup (AV) angles. Measurements were done pre-operatively and at 6 weeks, and at five and ten years post-operatively. Three measurements were recorded and the mean obtained at all intervals. All radiographs were evaluated by the same author, who was not involved in the surgery.

There were nine dislocations: six were solved with closed reduction, and three required cup revision. All the mean angles changed over time; the SFP angle from 59.2º to 60º (p=0.249), the AA angle from 44.5º to 46.8º (p=0.218), and the AV angle from 14.7º to 16.2º (p=0.002). The SFP angle was lower in older patients at all intervals (p<0.001). The SFP angle changed from 63.8 to 60.4º in women and from 59.4º to 59.3º in men, from 58.6º to 59.6º (p=0.012). The SFP angle changed from 62.7º to 60.9º in patients without lumbar pathology, from 58.6º to 57.4º in patients with lumbar pathology, and from 57.0º to 56.4º in patients with a lumbar fusion (p=0.919). The SFP cup angle was higher in patients without lumbar pathology than in the other groups (p<0.001), however, it changed more than in patients with lumbar pathology or fusion at ten years after THA (p=0.04).

Posterior pelvic tilt changed with aging, influencing the cup position in patients after a THA. Changes due to lumbar pathology could influence the appearance of complications long-term.

Lumbar diseases have become a major problem affecting human health worldwide. Conservative treatment of lumbar diseases is difficult to achieve ideal results, and surgical treatment of trauma, complications, it is imperative to develop a new treatment method. This study aims to explore the regulatory mechanism of cartilage endplate ossification caused by abnormal stress, and design intervention targets for this mechanism, so as to provide theoretical reference for the prevention and treatment of lumbar degeneration.

In vivo, we constructed spinal instability model in mice. In vitro, we used a mechanical tensile machine to simulate the abnormal stress conditions of the endplate cartilage cells. Through the high-throughput sequencing, we found the enrichment of Hippo signaling pathway. As YAP is a key protein in the Hippo signaling pathway, we then created cartilaginous YAP elimination mice (Col2::YAPfl/fl). The lumbar spine model was constructed again in these mice for H&E, SOFG and immunofluorescence staining. In vitro lentivirus was used to knock out YAP, immunofluorescence staining, WB and qPCR were performed. Finally, we conducted therapeutic experiments by using YAP agonist and AAV5 carrying YAP plasmids.

We collected 8w samples from C57/BL6 mice after modeling. We found ossification of the endplate in mice similar to human disc degeneration. High-throughput sequencing of stretched cells demonstrated high enrichment of the Hippo signaling pathway. By immunofluorescence staining, it was confirmed that Col-II decreased and Col-X gradually increased in the endplate cartilage of mice. This was also confirmed at 7 days after an in vitro stretch of 5% and 12%. Meanwhile, we found that cartilaginous YAP elimination mice developed very severe endplate degeneration. However, the endplate was well protected by intraperitoneal injection of YAP agonist or AAV5-YAP endplate injection, and the results in vitro were consistent with that.

In the process of cartilaginous ossification, abnormal stress regulates Col10a1 to promote cartilage endplate ossification through Hippo signaling pathway mediated YAP, and we expect to find potential drug targets for treatment through this mechanism.

We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age.

Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts.

Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency.

Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers.

These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis.

Conventional proximal tibial osteotomy is a widely successful joint-preserving treatment for osteoarthritis; however, conventional procedures do not adequately control the posterior tibial slope (PTS). Alterations to PTS can affect knee instability, ligament tensioning, knee kinematics, muscle and joint contact forces as well as range of motion.

This study primarily aimed to provide a comprehensive investigation of the variables influencing PTS during high tibial osteotomy using a 3D surgical simulation approach. Secondly, it aimed to provide a simple means of implementing the findings in future 3D pre-operative planning and /or clinically.

The influence of two key variables: the gap opening angle and the hinge axis orientation on PTS was investigated using three independent approaches: (1) 3D computational simulation using CAD software to perform virtual osteotomy surgery and simulate the post-operative outcome. (2) Derivation of a closed-form mathematical solution using a generalised vector rotation approach (3) Clinical assessment of synthetically generated x-rays of osteoarthritis patients (n=28; REC reference: 17/HRA/0033, RD&E NHS, UK) for comparison against the theoretical/computational approaches.

The results from the computational and analytical assessments agreed precisely. For three different opening angles (6°, 9° and 12°) and 7 different hinge axis orientations (from −30° to 30°), the results obtained were identical. A simple analytical solution for the change in PTS, ΔP_s, based on the hinge axis angle, α, and the osteotomy opening angle, θ, was derived:

ΔP_s=sin^-1(sin α sin θ)

The clinical assessment demonstrated that the absolute values of PTS, and changes resulting from various osteotomies, matched the results from the two relative prediction methods.

This study has demonstrated that PTS is impacted by the hinge axis angle and the extent of the osteotomy opening angle and provided computational evidence and analytical formula for general use.

Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms.

Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment.

CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies).

CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.

In a clinical setting, there is a need for simple gait kinematic measurements to facilitate objective unobtrusive patient monitoring. The objective of this study is to determine if a learned classification model's output can be used to monitor a person's recovery status post-TKA.

The gait kinematics of 20 asymptomatic and 17 people with TKA were measured using a full-body Xsens model¹. The experimental group was measured at 6 weeks, 3, 6, and 12 months post-surgery. Joint angles of the ankle, knee, hip, and spine per stride (10 strides) were extracted from the Xsens software (MVN Awinda studio 4.4)¹.

Statistical features for each subject at each evaluation moment were derived from the kinematic time-series data. We normalised the features using standard scaling². We trained a logistic regression (LR) model using L1-regularisation on the 6 weeks post-surgery data2–4.

After training, we applied the trained LR- model to the normalised features computed for the subsequent timepoints. The model returns a score between 0 (100% confident the person is an asymptomatic control) and 1 (100% confident this person is a patient). The decision boundary is set at 0.5.

The classification accuracy of our LR-model was 94.58%. Our population's probability of belonging to the patient class decreases over time. At 12 months post-TKA, 38% of our patients were classified as asymptomatic.

There is no consensus on how to evaluate and grade pin site infection. A precise, objective and reliable pin site infectious score is warranted. The literature was reviewed for pin site infection classification systems, The Modified Gordon Score (MGS) grade 0-6 was used. The aim was to test the reliability of The Modified Gordon Infection Score. The observed agreement and inter-rater reliability were investigated between nurse and doctors.

MGS was performed in the outpatient clinic at Aalborg University Hospital, Denmark on 1472 pin sites in 119 patients by one nurse and one of three orthopaedic surgeons blinded to each other's judgement. The data was stored in a Red Cap Database for further statistical analysis. The observed agreement between the nurse and the 3 orthopaedic surgeons was evaluated with a one-way random-effect model with interclass correlation with absolute agreement. Furthermore the observed agreement for each of the 3 surgeons with the nurse was calculated.

The distribution of MGS infection grade in the 1472 pin sites was: Grade 0; n=1372, Grade 1; n=32, Grade 2; n=39, Grade 3; n=24, Grade 4; n=5, Grade 5; n=0, Grade 6; n=0.

The observed agreement between the nurse and the surgeons was calculated as 98%. The ICC estimated between nurse and the surgeons was 0,8943 (ICC >0,85 = reliable). The grading was done by three different doctors with an agreement with the nurse as follows. Rater1 (n=416) =99,5 %, Rater2 (n=1440) =97,4%, Rater3 (n=1440) =96,6%.

A limitation to this study is that the dataset represents mostly clean pin sites with MGS 0. Only 100 pin sites had signs of superficial infection MGS 1-4 none above 4. We found that the MGS infection score is highly reliable for low grade infections but we cannot conclude on reliability in severe infections.

To detect early signs of infection infrared thermography has been suggested to provide quantitative information. Our vision is to invent a pin site infection thermographic surveillance tool for patients at home. A preliminary step to this goal is the aim of this study, to automate the process of locating the pin and detecting the pin sites in thermal images efficiently, exactly, and reliably for extracting pin site temperatures.

A total of 1708 pin sites was investigated with Thermography and augmented by 9 different methods in to totally 10.409 images. The dataset was divided into a training set (n=8325), a validation set (n=1040), and a test set (n=1044) of images. The Pin Detection Model (PDM) was developed as follows: A You Only Look Once (YOLOv5) based object detection model with a Complete Detection Intersection over Union (CDIoU), it was pre-trained and finetuned by the through transfer learning. The basic performance of the YOLOv5 with CDIoU model was compared with other conventional models (FCOS and YOLOv4) for deep and transition learning to improve performance and precision. Maximum Temperature Extraction (MTE) Based on Region of Interest (ROI) for all pin sites was generated by the model. Inference of MTE using PDM with infected and un-infected datasets was investigated.

An automatic tool that can identify and annotate pin sites on conventional images using bounding boxes was established. The bounding box was transferred to the infrared image. The PMD algorithm was built on YOLOv5 with CDIoU and has a precision of 0.976. The model offers the pin site detection in 1.8 milliseconds. The thermal data from ROI at the pin site was automatically extracted.

These results enable automatic pin site annotation on thermography. The model tracks the correlation between temperature and infection from the detected pin sites and demonstrates it is a promising tool for automatic pin site detection and maximum temperature extraction for further infection studies. Our work for automatic pin site annotation on thermography paves the way for future research on infection assessment using thermography.

Fragility ankles fractures in the geriatric population are challenging to manage, due to fracture instability, soft tissue compromise, patient co-morbidities. Traditional management options include open reduction internal fixation, or conservative treatment, both of which are fraught with high complication rates. We aimed to present functional outcomes of elderly patients with fragility ankle fractures treated with tibiotalocalcaneal nails.

171 patients received a tibiotalocalcaneal nail over a six-year period, but only twenty met the inclusion criteria of being over sixty and having poor bone stock, verified by radiological evidence of osteopenia or history of fragility fractures. Primary outcome was mortality risk from co-morbidities, according to the Charlson co-morbidity index (CCI), and patients’ post-operative mobility status compared to pre-operative mobility. Secondary outcomes include intra-operative and post-operative complications, six-month mortality rate, time to mobilisation and union.

The mean age was 77.82 years old, five of whom are type 2 diabetics. The average CCI was 5.05. Thirteen patients returned to their pre-operative mobility state. Patients with low CCI are more likely to return to pre-operative mobility status (p=0.16; OR=4.00).

Average time to bone union and mobilisation were 92.5 days and 7.63 days, respectively. Mean post-operative AOFAS ankle-hindfoot and Olerud-Molander scores were 53.0 (range 17-88) and 50.9 (range 20-85), respectively. There were four cases of broken distal locking screws, and four cases of superficial infection. Patients with high CCI were more likely to acquire superficial infections (p=0.264, OR=3.857). There were no deep infections, periprosthetic fractures, nail breakages, non-unions.

TTC nailing is an effective treatment methodology for low-demand geriatric patients with fragility ankle fractures. This technique leads to low complication rates and early mobilisation. It is not a life-changing procedure, with many able to return to their pre-operative mobility status, which is important for preventing the loss of socioeconomic independence.

A major cause of morbidity in lower limb amputees is phantom limb pain (PLP) and residual limb pain (RLP). This study aimed to determine if surgical interposition of nerve endings into adjacent muscle bellies at the time of major lower limb amputation can decrease the incidence and severity of PLP and RLP.

Data was retrospectively collected from January 2015 to January 2021, including eight patients that underwent nerve interposition (NI) and 36 that received standard treatment. Primary outcomes included the 11-point Numerical Rating Scale (NRS) for pain severity, and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behaviour, and interference. Secondary outcome included Neuro-QoL Lower Extremity Function assessing mobility. Cumulative scores were transformed to standardised t scores.

Across all primary and secondary outcomes, NI patients had lower PLP and RLP. Mean ‘worst pain’ score was 3.5 out of 10 for PLP in the NI cohort, compared to 4.89 in the control cohort (p=0.298), and 2.6 out of 10 for RLP in the NI cohort, compared to 4.44 in the control cohort (p=0.035). Mean ‘best pain’ and ‘current pain’ scores were also superior in the NI cohort for PLP (p=0.003, p=0.022), and RLP (p=0.018, p=0.134).

Mean PROMIS t scores were lower for the NI cohort for RLP (40.1 vs 49.4 for pain intensity; p=0.014, 44.4 vs 48.2 for pain interference; p=0.085, 42.5 vs 49.9 for pain behaviour; p=0.025). Mean PROMIS t scores were also lower for the NI cohort for PLP (42.5 vs 52.7 for pain intensity; p=0.018); 45.0 vs 51.5 for pain interference; p=0.015, 46.3 vs 51.1 for pain behaviour; p=0.569). Mean Neuro-QoL t score was lower in NI cohort (45.4 vs 41.9;p=0.03).

Surgical interposition of nerve endings during lower limb amputation is a simple yet effective way of minimising PLP and RLP, improving patients’ subsequent quality of life. Additional comparisons with targeted muscle reinnervation should be performed to determine the optimal treatment option.

Evidence supporting the use of virtual reality (VR) training in orthopaedic procedures is rapidly growing. However, the impact of the timing of delivery of this training is yet to be tested. We aimed to investigate whether spaced VR training is more effective than massed VR training.

24 medical students with no hip arthroplasty experience were randomised to learning the direct anterior approach total hip arthroplasty using the same VR simulation, training either once-weekly or once-daily for four sessions. Participants underwent a baseline physical world assessment on a saw bone pelvis. The VR program recorded procedural errors, time, assistive prompts required and hand path length across four sessions. The VR and physical world assessments were repeated at one-week, one-month, and 3 months after the last training session.

Baseline characteristics between the groups were comparable (p > 0.05). The daily group demonstrated faster skills acquisition, reducing the median ± IQR number of procedural errors from 68 ± 67.05 (session one) to 7 ± 9.75 (session four), compared to the weekly group's improvement from 63 ± 27 (session one) to 13 ± 15.75 (session four), p < 0.001. The weekly group error count plateaued remaining at 14 ± 6.75 at one-week, 16.50 ± 16.25 at one-month and 26.45 ± 22 at 3-months, p < 0.05. However, the daily group showed poorer retention with error counts rising to 16 ± 12.25 at one-week, 17.50 ± 23 at one-month and 41.45 ± 26 at 3-months, p<0.01. A similar effect was noted for the number of assistive prompts required, procedural time and hand path length. In the real-world assessment, both groups significantly improved their acetabular component positioning accuracy, and these improvements were equally maintained (p<0.01).

Daily VR training facilitates faster skills acquisition; however weekly practice has superior skills retention.

Osteochondral injuries are a recognised factor in the development of osteoarthritis (OA). Mesenchymal stromal cells (MSCs) represent a promising biological therapeutic option as an OA-modifying treatment, and they also secrete factors that may have an anti-catabolic effect and/or encourage endogenous repair. We aim to study the effects of (i) intra-articular injection of human bone-marrow-derived MSCs and (ii) their secretome on recovery in a murine knee osteochondral injury model.

The MSC secretome was generated by stimulating human bone-marrow-derived MSCs with tumour necrosis factor alpha (TNFα). Mice (n=48) were injected with i) MSC secretome, ii) MSCs or iii) cell culture medium (control). Pain was assessed by activity monitoring, and cartilage repair, subchondral bone volume and synovial inflammation were evaluated using histology and microCT.

Both MSC- and MSC-secretome-injected mice showed significant pain reduction at day 7 when compared to control mice, but only the MSC-injected mice maintained a significant improvement over the controls at day 28. Cartilage repair was significantly improved in MSC-injected mice. No significant effects were observed with regards to synovial inflammation or subchondral bone volume.

The MSC secretome demonstrates regenerative effects but this does not appear to be as sustained as a MSC cell therapy. Further studies are required to investigate if this can be overcome using different dosing regiments for injection of the MSC secretome. As we further understand the regenerative properties of the MSC secretome, we may be able to enhance the clinical translatability of these therapies. Direct intra-articular injection of MSCs for the treatment of OA also appears promising as a potential future strategy for OA management.

Acknowledgements: MS is supported by a grant from the Wellcome Trust (PhD Programme for Clinicians)

Many age-related diseases affect our skeletal system, but bone health-targeting drug development strategies still largely rely on 2D in vitro screenings. We aimed at developing a scaffold-free progenitor cell-based 3D biomineralization model for more physiological high-throughput screenings.

MC3T3-E1 pre-osteoblast spheroids were cultured in V-shaped plates for 28 days in alpha-MEM (10% FCS, 1% L-Gln, 1X NEAA) with 1% pen/strep, changed every two days, and differentiation was induced by 10mM b-glycerophosphate and 50µg/ml ascorbic-acid. Osteogenic cell differentiation was assessed through profiling mRNA expression of selected osteogenic markers by efficiency corrected normalized 2^DDCq RT-qPCR. Biomineralization in spheroids was evaluated by histochemistry (Alizarin Red/von Kossa staining), Alkaline phosphatase (Alp) activity, Fourier transform infrared spectroscopy (FTIR) analyses, micro-CT analyses, and scanning electron microscopy on critical point-dried samples. GraphPad Prism 9 analyses comprised Shapiro-Wilk and Brown-Forsythe tests as well as 2-way ANOVA with Tukey post-hoc and non-parametric Kruskal-Wallis with Dunn post-hoc tests.

During mineralization, as opposed to non-mineralizing conditions, characteristic mRNA expression profiles of selected early and late osteoblast differentiation markers (e.g., RunX, Alp, Col1a1, Bglap) were observed between day 0 and 28 of culture; Alp was strongly upregulated (p<0.001) from day 7 on, followed by its enzymatic activity (p<0.001). Bglap and Col1a1 expression peaked on (p<0.001) and from day 14 on (p<0.05), respectively. IHC revealed osteocalcin staining in the spheroid core regions at day 14, while type I collagen staining of the cores was most prominent from day 21 on. Alizarin Red and Von Kossa confirmed central and radially outwards expanding mineralization patterns between day 14 and day 28, which was accompanied by a steady increase in extracellular calcium deposition over time (p<0.001). Micro-CT analyses allowed quantitative appreciation of the overall increase in mineral density over time (day21, p<0.05; d28, p<0.001), while SEM-EDX and FTIR ultimately confirmed a bone-like hydroxyapatite mineral deposition in 3D.

A novel and thoroughly characterized versatile bone-like 3D biomineralization in vitro model was established, which allows for studying effects of pharmacological interventions on bone mineralization ex vivo under physiomimetic conditions. Ongoing studies currently aim at elucidating in how far it specifically recapitulates intramembranous ossification.

Miniscrew implants (MSIs) are widely used to provide absolute anchorage for the orthodontic treatment. However, the application of MSIs is limited by the relatively high failure rate (22.86%). In this study, we wished to investigate the effects of amorphous and crystalline biomimetic calcium phosphate coating on the surfaces of MSIs with or without the incorporated BSA for the osteointegration process with an aim to facilitate the early loading of MSIs.

Amorphous and crystalline coatings were prepared on titanium mini-pin implants. Characterizations of coatings were examined by Scanning electron microscopy (SEM), Confocal laser-scanning dual-channel-fluorescence microscopy (CLSM) and Fourier-transform infrared spectroscopy (FTIR). The loading and release kinetics of bovine serum albumin (BSA) were evaluated by Enzyme linked immunosorbent assay (ELISA). Activity of alkaline phosphate (ALP) was measured by using the primary osteoblasts. In vivo, a model of metaphyseal tibial implantation in rats was used (n=6 rats per group). We had 6 different groups: no coating no BSA, no coating but with surface adsorption of BSA and incorporation of BSA in the biomimetic coating in the amorphous and crystalline coatings. Time points were 3 days, 1, 2 and 4 weeks. Histological and histomorphometric analysis were performed and the bone to implant contact (BIC) of each group was compared.

In vitro, the incorporation of BSA changed the crystalline coating from sharp plates into curly plates, and the crystalline coating showed slow-release profile. The incorporation of BSA in crystalline coating significantly decreased the activity of ALP in vitro. In vivo study, the earliest significant increase of BIC appeared in crystalline coating group at one week.

The crystalline coating can serve as a carrier and slow release system for the bioactive agent and accelerate osteoconductivity at early stage in vivo. The presence of BSA is not favorable for the early establishment of osteointegration.

Proximal humeral shaft fractures are commonly treated with long straight plates or intramedullary nails. Helical plates might overcome the downsides of these techniques as they are able to avoid the radial nerve distally. The aim of this study was to investigate in an artificial bone model: (1) the biomechanical competence of different plate designs and (2) to compare them against the alternative treatment option of intramedullary nails.

Twenty-four artificial humeri were assigned in 4 groups and instrumented as follows: group1 (straight 10-hole-PHILOS), group2 (MULTILOCK-nail), group3 (45°-helical-PHILOS) and group4 (90°-helical-PHILOS). An unstable proximal humeral shaft fracture was simulated. Specimens were tested under quasi-static loading in axial compression, internal/external rotation and bending in 4 directions monitored by optical motion tracking.

Axial displacement (mm) was significantly lower in group2 (0.1±0.1) compared to all other groups (1: 3.7±0.6; 3: 3.8±0.8; 4: 3.5±0.4), p<0.001. Varus stiffness in group2 (0.8±0.1) was significantly higher compared to groups1+3, p≤0.013 (1: 0.7±0.1; 3: 0.7±0.1; 4: 0.8±0.1). Varus bending (°) was significantly lower in group2 compared to all other groups (p<0.001) and group4 to group1, p=0.022. Flexion stiffness in group1 was significantly higher compared to groups2+4 (p≤0,03) and group4 to group1, p≤0,029 (1: 0.8±0.1; 2: 0.7±0.1; 3: 0.7±0.1; 4: 0.6±0.1). Flexion bending (°) in group4 was higher compared to all other groups (p≤0.024) and lower in group2 compared to groups1+4, p≤0.024. Torsional stiffness remained non significantly different, p≥0.086. Torsional deformation in group2 was significantly higher compared to all other groups, p≤0.017. Shear displacement remained non significantly different, p≥0.112.

From a biomechanical perspective, helical plating with 45° and 90° may be considered as a valid alternative fixation technique to standard straight plating of proximal third humeral fractures. Intramedullary nails demonstrated higher axial and bending stiffness as well as lower fracture gap movements during axial loading compared to all plate designs. However, despite similar torsional stiffness they were associated with higher torsional movements during internal/external rotation as compared to all investigated plate designs.

COVID-19 was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The initial response to the pandemic included the cessation of routine services including elective orthopaedic surgery. There was apprehension among both surgeons and patients about restarting elective surgical services. The high mortality rate in perioperative patients who contract COVID-19 was of particular concern. The aim of this study was to identify the perioperative viral transmission rate in orthopaedic patients at our institution following the restart of elective surgery between August 2020 and November 2020 after the first wave of Covid in the UK.

All patients who had their elective Orthopaedic surgeries at our institution from 1st August 2020 to 30th November 2020 were checked whether they were Covid positive or experienced COVID symptoms within 2 weeks after the operation. All patients were advised a 14-day period of comprehensive social distancing, 3 days of self-isolation and had a negative COVID-19 test within 72 hours of surgery and underwent surgery at a COVID free site. The patients were contacted and the hospital database was searched to identify those patients who were Covid positive or had Covid symptoms after the surgery. Baseline patient characteristics were recorded including age, gender, procedure, the subspeciality and admission type. Patients who underwent emergency procedures and trauma operations were excluded.

Out of the 499 patients, 315 were contacted over telephone and hospital database was searched for the rest of the patients. We found that none of the patients were positive for COVID or had symptoms of COVID within two weeks of surgery. 5 patients were COVID positive with symptoms few months after the procedure and all of them recovered. There were 144 inpatient admissions and 353 day cases.

The development of a COVID-free pathway for elective orthopaedic patients results in very low viral transmission rates. Findings of our study confirms that COVID-free elective pathway is an efficient process, and this could be implemented in future elective Orthopaedic surgeries during COVID times. Elective surgery can be safely resumed using dedicated pathways and procedures -Surgeons, hospital staff and patients should remain vigilant.

Aseptic inflammation is the main factor causing aseptic loosening of artificial joints. Studies have shown that inflammatory cells can activate STING (stimulator of interferon genes, STING) after being stressed. This study aims to explore the specific mechanism of STING in aseptic loosening of artificial joints, and provide new strategies for disease prevention.

Titanium particles with a diameter of 1.2-10 μm were prepared to stimulate macrophages (RAW 264.7) to simulate the periprosthetic microenvironment. A lentiviral vector targeting the STING gene was designed and transfected into macrophages to construct a cell line targeting STING knockdown. The expression and secretion levels of TNF-α were detected by qPCR and ELISA, the activation levels of inflammatory pathways (NF-κB, IRF3, etc.) were detected by western blot, and the nucleus translocation of P65 and IRF3 was observed by cellular immunofluorescence.

After titanium particles stimulated macrophages, qPCR and ELISA showed that the transcription and secretion levels of TNF-α were significantly increased. Western blot showed that titanium particle stimulation could increase the phosphorylation levels of NF-κB and IRF3 pathways. While knockdown of STING can significantly reduce titanium particle-induced TNF production, attenuate the activation levels of NF-κB and IRF3 pathways as well as the nucleus translocation of P65 and IRF3.

Conclusions: STING positively regulates the level of inflammation in macrophages induced by titanium particles, and targeted inhibition of STING can reduce inflammation, which may delay the progression of aseptic loosening of artificial joints.

Intervertebral disc degeneration (IDD), the main cause of low back pain, is closely related to the inflammatory microenvironment in the nucleus pulposus (NP). Tumor necrosis factor-α (TNF-α) plays an important role in inflammation-related metabolic disturbance of NP cells. Melatonin has been proven to regulate the metabolism of NP cells, but whether it can protect NP cells from TNF-α-induced damage is still unclear. Therefore, this study aims to investigate the role and specific mechanism of melatonin on regulating the metabolism of NP cells in the inflammatory microenvironment.

Human primary NP cells were treated with or without vehicle, TNF-α and melatonin. And the metabolic markers were also detected by western blotting and RT-qPCR. The activity of NF-κB signaling and Hippo/YAP signaling were assessed by western blotting and immunofluorescence. Membrane receptors inhibitors, pathway inhibitors, lentiviral infection, plasmids transfection and immunoprecipitation were used to explore the specific mechanism of melatonin. In vivo, the rat IDD model were constructed and melatonin was injected intraperitoneally to evaluate its therapeutical effect on IDD.

We demonstrated that melatonin could alleviate the development of IDD in a rat model and reverse TNF-α–impaired metabolism of NP cells in vitro. Further investigation revealed that the protective effects of melatonin on NP cells mainly rely on MTNR1B, which subsequently activates Gαi2 protein. The activation of Gαi2 could upregulate the yes-associated protein (YAP) level, resulting in anabolic enhancement of NP cells. In addition, melatonin-mediated YAP upregulation increased the expression of IκBα and suppressed the TNF-α–induced activation of the NF-κB pathway, thereby inhibiting the catabolism of NP cells.

Our results revealed that melatonin can reverse TNF-α–impaired metabolism of NP cells via the MTNR1B/Gαi2/YAP axis and suggested that melatonin can be used as a potential therapeutic drug in the treatment of IDD.

Lesions in the joint surface are commonly treated with osteoarticular autograft transfer system (OATS), autologous cell implantation (ACI/MACI), or microfracture. Tissue formed buy the latter commonly results in mechanically inferior fibrocartilage that fails to integrate with the surrounding native cartilage, rather than durable hyaline cartilage. Fractional laser treatment to make sub-millimeter (<500 µm) channels has been employed for tissue regeneration in the skin to facilitate rejuvenation without typical scarring. Additionally, we have pioneered a means to generate articular cartilage matrix from chondrocytes—dynamic Self-Regenerating Cartilage (dSRC). Combining these two approaches by performing fractional laser treatment of the joint cartilage and treating with dSRC is a new paradigm for joint surface restoration. This approach was refined in a series of in vitro experiments and tested in swine knee defects during a 6-month study in 12 swine.

dSRC are generated by placing 10⁷ swine knee chondrocytes into sealed 15-mL polypropylene tubes and cultured on a rocker at 40 cycles per minute for 14 days at 37°C. The chondrocytes aggregate and generate new extracellular matrix to form a pellet of dSRC. Channels of approximately 300-500 µm diameter were created by infrared laser ablation in swine cartilage (in vitro) and swine knees (in vivo). The diameter and depth of the ablated channel in the cartilage was controlled by the light delivery parameters (power, spot size, pulse duration) from a fractional 2.94 µm Erbium laser. The specimens were evaluated with histology (H&E, safranin O, toluidine blue) and polarized-sensitive optical coherence tomography for collagen orientation.

We can consistently create laser-ablated channels in the swine knee and successfully implant new cartilage from dSRC to generate typical hyaline cartilage in terms of morphology and biochemical properties. The neocartilage integrates with host cartilage in vivo.

These findings demonstrate our novel combinatorial approach for articular cartilage rejuvenation.

Obesity is associated with poor outcomes and increased risk of failure after rotator cuff (RC) repair surgery. The effect of diet-induced obesity (DIO) on enthesis healing has not been well characterised and whether its effects can be reversed with dietary intervention is unknown. We hypothesised that DIO would result in inferior enthesis healing in a rat model of RC repair and that dietary intervention in the peri-operative period would improve enthesis healing.

A total of 78 male Sprague-Dawley rats were divided into three weight-matched groups from weaning and fed either: control diet (CD), high-fat diet (HFD), or HFD until surgery, then CD thereafter (HF-CD). After 12 weeks the left supraspinatus tendon was detached, followed by immediate surgical repair. At 2 and 12 weeks post-surgery, animals were cullers and RCs harvested for biomechanical and histological evaluation. Body composition and metabolic markers were assessed via DEXA and plasma analyses, respectively.

DIO was established in the HFD and HF-CD groups prior to surgery, and subsequently reversed in the HF-CD group after surgery. At 12 weeks post-surgery, plasma leptin concentrations were higher in the HFD group compared to the CD group (5.28 vs. 2.91ng/ml, P=0.003). Histologically, the appearance of the repaired entheses was poorer in both the HFD and HF-CD compared to the CD group at 12 weeks (overall histological score 6.20 (P=0.008), 4.98 (P=0.001) and 8.68 out of 15, respectively). The repaired entheses in the HF-CD group had significantly lower (26.4 N, P=0.028) load-at-failure 12 weeks post-surgery compared to the CD group (34.4 N); while the HFD group was low, but not significantly different (28.1 N, P=0.096). Body mass at the time of surgery, plasma leptin and body fat percentage were negatively correlated with histological scores and plasma leptin with load-at-failure 12 weeks post-surgery.

DIO impaired enthesis healing in this rat RC repair model, with inferior biomechanical and histological outcomes. Restoring normal weight with dietary change after surgery did not improve healing outcomes. Exploring interventions that improve the metabolic state of obese patients and counselling patients appropriately about their modest expectations after repair should be considered.

This study aims to assess the fracture mechanics of type-2 diabetic (T2D) femoral bone using innovative site-specific tests, whilst also examining the cortical and trabecular bone microarchitecture from various regions using micro-computed tomography (CT) of the femur as the disease progresses.

Male [Zucker Diabetic Fatty (ZDF: fa/fa) (T2D) and Zucker Lean (ZL: fa/+) (Control)] rats were euthanized at 12-weeks of age, thereafter, right and left femora were dissected (Right femora: n = 6, per age, per condition; Left femora: n=8-9, per age, per condition). Right femurs were notched in the posterior of the midshaft. Micro-CT was used to scan the proximal femur, notched and unnotched femoral midshaft (cortical) of the right femur and the distal metaphysis (trabecular) of the left femur to investigate microarchitecture and composition. Right femurs were fracture toughness tested to measure the stress intensity factor (Kic) followed by a sideways fall test using a custom-made rig to investigate femoral neck mechanical properties.

There was no difference in trabecular and cortical tissue material density (TMD) between T2D and control rats. Cortical thickness was unchanged, but trabeculae were thinner (p<0.01) in T2D rats versus controls. However, T2D rats had a greater number of trabeculae (p<0.05) although trabecular spacing was not different to controls. T2D rats had a higher connectivity distribution (p<0.05) and degree of anisotropy (p<0.05) in comparison to controls. There was no difference in the mechanical properties between strains.

At 12-weeks of age, rats are experiencing early-stage T2Ds and the disease impact is currently not very clear. Structural and material properties are unchanged between strains, but the trabecular morphology shows that T2D rats have more trabecular struts present in order to account for the thinner trabeculae.

Irrigation with antiseptic agents, antibiotics, and surfactants are used for treatment and prevention of infections. Despite desirable microbicidal actions, studies have demonstrated cytotoxic effects on host tissue that may impair healing. This study investigated the extent of tissue damage caused by commonly used irrigation solutions in the presence or absence of infection.

Air pouches created in 60 balb/c mice were divided into two groups (n=30): infected with Staphylococcus aureus and control. One week later the infected group was subdivided into 5 subgroups (n=6) based on irrigation solutions and by day 0 (immediately) and day7 after irrigation (n=3). Solutions included Saline, Bacitracin, Clorpactin, Irrisept and Bactisure. In infected group wash fluid was collected for quantitative analysis of bacterial growth. At the specified times mice were sacrificed, pouch tissue sent for histology, and sections analyzed for inflammation, necrosis, and edema.

Inflammation decreased in infected vs sterile pouches for all solutions except Bacitracin day 0 and for all solutions day 7 with significance in all except Bacitracin (p<0.05). On day 0, necrosis increased in infected vs sterile pouches in Bacitracin (p=0.006), Irrisept (p=0.18), or Bactisure (p=0.07); however, on day 7, necrosis significantly decreased in infected pouches for all solutions (p<0.05) except for Clorpactin (p=0.18). Edema decreased in infected vs sterile pouches on day 0 for all solutions with significance in saline, Irrisept, and Bacitracin (p<0.05). On day 7, infected pouches had decreased edema in saline, Bacitracin, and Bactisure (p<0.05) and increased in Irrisept (p<0.05) and Clorpactin (p=0.069) compared to sterile pouches. Bacterial culture of washouts demonstrated that Clorpactin, Irrisept and Bactisure controlled the infection, whereas saline and Bacitracin showed bacterial multiplication 3.9 × 10^7 CFU/ml and 6.7 × 10^7 CFU/ml respectively. Bacitracin wash showed significantly more bacteria growth compared to Clorpactin (p=0.024), Irrisept (p=0.025) and Bactisure (p=0.025).

Tissue damage varied with irrigation solutions and the presence or absence of infection. Presence of bacteria appeared to lead to less tissue inflammation and edema. Tissue necrosis varied over time with different solutions. Surgeons must weigh risks and benefits when selecting solutions and determining when to irrigate.

Senescent chondrocyte and subchondral osteoclast overburden aggravate inflammatory cytokine and pro-catabolic proteinase overproduction, accelerating extracellular matrix degradation and pain during osteoarthritis (OA). Fibronectin type III domain containing 5 (FNDC5) is found to promote tissue homeostasis and alleviate inflammation. This study aimed to characterize what role Fndc5 may play in chondrocyte aging and OA development.

Serum and macroscopically healthy and osteoarthritic cartilage were biopsied from patients with knee OA who received total knee replacement. Murine chondrocytes were transfected with Fndc5 RNAi or cDNA. Mice overexpressing Fndc5 (Fndc5Tg) were operated to have destabilized medial meniscus mediated (DMM) joint injury as an experimental OA model. Cellular senescence was characterized using RT-PCR analysis of p16INK4A, p21CIP1, and p53 expression together with ß-galactosidase activity staining. Articular cartilage damage and synovitis were graded using OARSI scores. Osteophyte formation and mechanical allodynia were quantified using microCT imaging and von Frey filament, respectively. Osteoclast formation was examined using tartrate-resistant acid phosphatase staining.

Senescent chondrocyte and subchondral osteoclast overburden together with decreased serum FNDC5 levels were present in human osteoarthritic cartilage. Fndc5 knockdown upregulated senescence program together with increased IL-6, MMP9 and Adamts5 expression, whereas Alcian blue-stained glycosaminoglycan production were inhibited. Forced Fndc5 expression repressed senescence, apoptosis and IL-6 expression, reversing proliferation and extracellular matrix production in inflamed chondrocytes. Fndc5Tg mice showed few OA signs, including articular cartilage erosion, synovitis, osteophyte formation, subchondral plate sclerosis and mechanical allodynia together with decreased IL-6 production and few senescent chondrocytes and subchondral osteoclast formation during DMM-induced joint injury. Mechanistically, Fndc5 reversed histone H3K27me3-mediated IL-6 transcription repression to reduce reactive oxygen species production.

Fndc5 loss correlated with OA development. It was indispensable in chondrocyte growth and anabolism. This study sheds light onto the anti-ageing and anti-inflammatory actions of Fndc5 to chondrocytes; and highlights the chondroprotective function of Fndc5 to compromise OA.

Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor to maintain cellular redox homeostasis, but is also affecting bone metabolism. As the association between Nrf2 and osteoporosis in elderly females is not fully elucidated, our aim was to shed light on the potential contribution of Nrf2 to the development of age-dependent osteoporosis using a mouse model.

Female wild-type (WT, n=18) and Nrf2-knockout (KO, n=12) mice were sacrificed at different ages (12 weeks=young mature adult, and 90 weeks=old), morphological cortical and trabecular properties of femoral bone analyzed by micro-computed tomography (µCT), and compared to histochemistry. Mechanical properties were derived from quasi-static compression tests and digital image correlation (DIC) used to analyze full-field strain distribution. Bone resorbing cells and aromatase expression by osteocytes were evaluated immunohistochemically and empty osteocyte lacunae counted in cortical bone. Wilcoxon rank sum test was used for data comparison and differences considered statistically significant at p<0.05.

When compared to old WT mice, old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness (Ct.Th), cortical area (Ct.Ar), and cortical bone fraction (Ct.Ar/Tt.Ar). Surprisingly, these parameters were not different in skeletally mature young adult mice. Metaphyseal trabeculae were thin but present in all old WT mice, while no trabecular bone was detectable in 60% of old KO mice. Occurrence of empty osteocyte lacunae did not differ between both groups, but a significantly higher number of osteoclast-like cells and fewer aromatase-positive osteocytes were found in old KO mice. Furthermore, female Nrf2-KO mice showed an age-dependently reduced fracture resilience when compared to age-matched WT mice.

Our results confirmed lower bone quantity and quality as well as an increased number of bone resorbing cells in old female Nrf2-KO mice. Additionally, aromatase expression in osteocytes of old Nrf2-KO mice was compromised, which may indicate a chronic lack of estrogen in bones of old Nrf2-deficient mice. Thus, chronic Nrf2 loss seems to contribute to age-dependent progression of female osteoporosis.

Dual mobility hip arthroplasty utilizes a freely rotating polyethylene liner to protect against dislocation. As liner motion has not been confirmed in vivo, we investigated the liner kinematics in vivo using dynamic radiostereometry.

16 patients with Anatomical Dual Mobility acetabular components were included. Markers were implanted in the liners using a drill guide. Static RSA recordings and patient reported outcome measures were obtained at post-op and 1-year follow-up. Dynamic RSA recordings were obtained at 1-year follow-up during a passive hip movement: abduction/external rotation, adduction/internal rotation (modified FABER-FADIR), to end-range and at 45° hip flexion. Liner- and neck movements were described as anteversion, inclination and rotation.

Liner movement during modified FABER-FADIR was detected in 12 of 16 patients. Median (range) absolute liner movements were: anteversion 10° (5–20), inclination 6° (2–12), and rotation 11° (5–48) relative to the cup. Median absolute changes in the resulting liner/neck angle (small articulation) was 28° (12–46) and liner/cup angle (larger articulation) was 6° (4–21). Static RSA showed changes in median (range) liner anteversion from 7° (-12–23) postoperatively to 10° (-3–16) at 1-year follow-up and inclination from 42 (35–66) postoperatively to 59 (46–80) at 1-year follow-up. Liner/neck contact was associated with high initial liner anteversion (p=0.01).

The polyethylene liner moves over time. One year after surgery the liner can move with or without liner/neck contact. The majority of movement is in the smaller articulation between head and liner.

The aim of this research was to determine biomechanical markers which differentiate medial knee osteoarthritis (OA) patients who do and do not show structural progression over a 2-year period.

A cohort of 36 subjects was selected from a longitudinal study (Meireles et al 2017) using Kellgren-Lawrence (KL) scores at baseline and 2-year follow-up. The cohort consisted of 10 healthy controls (HC) (KL=0 at both time points), 15 medial knee OA non-progressors (NPKOA) (KL≥1 at baseline and no change over 2 years), and 11 medial knee OA progressors (PKOA) (KL≥1 at baseline and increase of ≥1 over 2 years). 3D integrated motion capture data from three walking trials were processed through a musculoskeletal modelling framework (Smith et al 2016) to estimate knee joint loading parameters (i.e., magnitude of mean contact pressure, and centre of pressure (COP)). Parameters at first and second peak were extracted and compared between groups using Kruskal-Wallis and Mann-Whitney tests.

Higher magnitudes were observed in PKOA vs NPKOA, and PKOA vs HC groups at both time points. Additionally, a posterior (1st and 2nd peak), and lateral (2nd peak) shift in medial compartment COP was shown between PKOA and NPKOA, and PKOA and HC subjects. Interestingly, in the studied parameters, no differences were observed between NPKOA and HC groups.

Significantly higher magnitude, and a more posterior and lateral COP was observed between PKOA and NPKOA patients. These differences, combined with an absence of difference between NPKOA and HC suggest structural OA progression is driven by a combination of altered loading magnitude and location. These results may serve as guidelines for targeted gait retraining rehabilitation to slow or stop knee OA progression whereby shifting COP anterior and medial and reducing magnitude by ~22% may shift patients from a PKOA to a NPKOA trajectory.

Implant manufacturers develop new products to improve existing fracture fixation methods or to approach new fracture challenges. New implants are commonly tested and approved with respect to their corresponding predecessor products, because the knowledge about the internal forces and moments acting on implants in the human body is unclear. The aim of this study was to evaluate and validate implant internal forces and moments of a complex physiological loading case and translate this to a standard medical device approval test.

A finite elements model for a transverse femur shaft fracture (AO/OTA type 32-B2) treated with a locked plate system (AxSOS 3 Ti Waisted Compression Plate Broad, Stryker, Kalamazoo, USA) was developed and experimentally validated. The fractured construct was physiologically loaded by resulting forces on the hip joint from previously measured in-vivo loading experiments (Bergmann et. al). The forces were reduced to a level where the material response in the construct remained linear elastic. Resulting forces, moments and stresses in the implant of the fractured model were analysed and compared to the manufacturers’ approval data.

The FE-model accurately predicted the behaviour of the whole construct and the micro motion of the working length of the osteosynthesis. The resulting moment reaction in the working length was 24 Nm at a load of 400 N on the hip. The maximum principle strains on the locking plate were predicted well and did not exceed 1 %.

In this study we presented a protocol by the example of locked plated femur shaft fracture to calculate and validate implant internal loading using finite element analysis of a complex loading. This might be a first step to move the basis of development of new implants from experience from previous products to calculation of mechanical behaviour of the implants and therefore, promote further optimization of the implants’ design.

Successful anterior cruciate ligament (ACL) reconstructions strive a firm ligament-bone integration. Therefore, the aim of this study was to address in more detail the enthesis as the thriphasic bone attachment of the ACL using a tissue engineering approach. To establish a tissue-engineered enthesis-like construct, triphasic scaffolds embroidered from poly(L-lactide-co-caprolactone) and polylactic acid functionalized with collagen foam were colonized with osteogenically differentiated human mesenchymal stromal cells (hMSCs) and lapine (L) ACL fibroblasts.

These triphasic scaffolds with a bone-, a fibrocartilage transition- and a ligament phase were seeded directly after spheroid assembly or with 14 days precultured LACL fibroblast spheroids and 14 days osteogenically differentiated hMSCs spheroids (=longer preculture) and cultured for further 14 days. Cell survival was tested. Collagen type I and vimentin were immunolabeled and the content of DNA and sulfated glycosaminoglycan (sGAG) was quantified. The relative gene expression of tenascin C, type I and X collagens, Mohawk and Runx2 was analyzed.

Compared to the LACL spheroids the hMSC spheroids adhered better to the scaffold surface with faster cell outgrowth on the fibers. Collagen type I and vimentin were mainly detected in the hMSCs colonizing the bone zone. The DNA content was generally higher in the bone (hMSCs) than in the ligament zones and after short spheroid preculture higher than after longer preculture whereas the sGAG content was greater after longer preculture for both cell types. The longer precultivated hMSCs expressed more type I collagen in comparison to those only shortly precultured before scaffold seeding. Type I collagen and tenascin C were higher expressed in scaffolds directly colonized with LACL compared to those seeded after longer spheroid preculture. The gene expression of ECM components and transcription factors depended on cell type and preculturing condition.

Zonal colonization of triphasic scaffolds using the spheroid method is possible offering a novel approach for enthesis tissue engineering.

High tibial osteotomy (HTO) is an effective surgical treatment for isolated medial compartment knee osteoarthritis; however, widespread adoption is limited due to difficulty in achieving the planned correction, and patient dissatisfaction due to soft tissue irritation. A new HTO system – Tailored Osteotomy Knee Alignment (TOKA®, 3D Metal Printing Ltd, Bath, UK) could potentially address these barriers having a custom titanium plate and titanium surgical guides featuring a unique mechanism for precise osteotomy opening as well as saw cutting and drilling guides. The aim of this study was to assess the accuracy of this novel HTO system using cadaveric specimens; a preclinical testing stage ahead of first-in-human surgery according to the ‘IDEAL-D’ framework for device innovation.

Local ethics committee approval was obtained. The novel opening wedge HTO procedure was performed on eight cadaver leg specimens. Whole lower limb CT scans pre- and post-operatively provided geometrical assessment quantifying the discrepancy between pre-planned and post-operative measurements for key variables: the gap opening angle and the patient specific surgical instrumentation positioning and rotation - assessed using the implanted plate.

The average discrepancy between the pre-operative plan and the post-operative osteotomy correction angle was: 0.0 ± 0.2°. The R2 value for the regression correlation was 0.95.

The average error in implant positioning was −0.4 ± 4.3 mm, −2.6 ± 3.4 mm and 3.1 ± 1.7° vertically, horizontally, and rotationally respectively.

This novel HTO surgery has greater accuracy and smaller variability in correction angle achieved compared to that reported for conventional or other patient specific methods with published data available. This system could potentially improve the accuracy and reliability of osteotomy correction angles achieved surgically.

A number of classification systems exist for posterior malleolus fractures of the ankle. The reliability of these classification systems remains unclear. The primary aim of this study was to evaluate the reliability of three commonly utilised fracture classification systems of the posterior malleolus.

60 patients across 2 hospitals sustaining an unstable ankle fracture with a posterior malleolus fragment were identified. All patients underwent radiographs and computed tomography of their injured ankle. 9 surgeons including pre-ST3 level, ST3-8 level, and consultant level applied the Haraguchi, Rammelt, and Mason & Molloy classifications to these patients, at two timepoints, at least 4 weeks apart. The order was randomised between assessments. Inter-rater reliability was assessed using Fleiss’ kappa and 95% confidence intervals (CI). Intra-rater reliability was assessed using Cohen's Kappa and standard error (SE).

Inter-rater reliability (Fleiss’ Kappa) was calculated for the Haraguchi classification as 0.522 (95% CI 0.490 – 0.553), for the Rammelt classification as 0.626 (95% CI 0.600 – 0.652), and the Mason & Molloy classification as 0.541 (95% CI 0.514 – 0.569). Intra-rater reliability (Cohen's Kappa) was 0.764 (SE 0.034) for the Haraguchi, 0.763 (SE 0.031) for the Rammelt, 0.688 (SE 0.035) for the Mason & Molloy classification.

This study reports the inter-rater and intra-rater reliability for three classification systems for posterior malleolus fractures. Based on definitions by Landis & Koch (1977), inter-rater reliability was rated as ‘moderate’ for the Haraguchi and Mason & Molloy classifications; and ‘substantial’ for the Rammelt classification. Similarly, the intra-rater reliability was rated as ‘substantial’ for all three classifications.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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