Introduction

Patellofemoral instability is one of the most common presentations to a children's orthopaedic clinic. Recurrent patellar dislocations and instability episodes are painful, disabling and increase the risk of irreversible chondral damage. The medial patellofemoral ligament is the primary static stabiliser to prevent lateral dislocation of the patella and is almost always torn or attenuated in these cases. Reconstruction of this ligament is commonly performed using autologous hamstring tendon however there has been some interest recently in use of quadriceps tendon as a graft. Children with patellar instability also present unique challenges due to the small size of the patella and the presence of open growth plates which may require adaptations to the common techniques.

Abstract

The triangular fibrocartilage complex (TFCC) is a known stabiliser of the distal radioulnar joint (DRUJ). An injury to these structures can result in significant disability including pain, weakness and joint stiffness. The contribution each of its components makes to the stability of the TFCC is not well understood. This study was undertaken to investigate the role of the individual ligaments of the TFCC and their contribution to joint stability.

The study was undertaken in two parts. 30 cadaveric forearms were studied in each group. The ligaments of the TFCC were progressively sectioned and the resulting effect on the stability of the DRUJ was measured. A custom jig was created to apply a 20N force through the distal radius, with the ulna fixed.

Experiment one measured the effect on DRUJ translation after TFCC sectioning. Experiment two added the measurement of rotational instability.

Part one of the study showed that complete sectioning of the TFCC caused a mean increase in translation of 6.09(±3) mm. Sectioning the palmar radioulnar ligament of the TFCC caused the most translation.

Part two demonstrated a change in rotation with a mean of 18 (± 6) degrees following sectioning of the TFCC. There was a progressive increase in rotational instability until the palmar radioulnar ligament was also sectioned.

Linear translation consistently increased after sectioning all of the TFCC ligaments, confirming its importance for DRUJ stability. Sectioning of the palmar radioulnar ligament most commonly caused the greatest degree of translation. This suggests injury to this ligament would more likely result in a greater degree of translational instability. The increase in rotation also suggests that this type of instability would be symptomatic in a TFCC injury.

Aim

Bacteriophages are remerging as alternative and adjunctive therapy for fracture-related infection (FRI). However, current administration protocols involve prolonged retention of a percutaneous draining tube with potential risk of developing superinfection. In this study, we applied a cocktail of in vitro evolved biofilm-targeting phages for Methicillin-resistant Staphylococcus aureus (MRSA) in a hydrogel platform co-delivering vancomycin. In vitro synergy and antibiofilm activity was assessed and a subsequent in vivo study was performed in a mouse FRI model with MRSA.

Custom acetabular components have become an established method of treating massive acetabular bone defects in hip arthroplasty. Complication rates, however, remain high and migration of the cup is still reported. Ischial screw fixation (IF) has been demonstrated to improve mechanical stability for non-custom, revision arthroplasty cup fixation. We hypothesise that ischial fixation through the flange of a custom acetabular component aids in anti-rotational stability and prevention of cup migration.

Electronic patient records were used to identify a consecutive series of 49 custom implants in 46 patients from 2016 to 2022 in a unit specializing in complex joint reconstruction. IF was defined as a minimum of one screw inserted into the ischium passing through a hole in a flange on the custom cup.

The mean follow-up time was 30 months. IF was used in 36 cups. There was no IF in 13 cups. No difference was found between groups in age (68.9 vs. 66.3, P = 0.48), BMI (32.3 vs. 28.2, P = 0.11) or number of consecutively implanted cups (3.2 vs. 3.6, P = 0.43). Aseptic loosening with massive bone loss was the primary indication for revision. There existed no difference in Paprosky grade between the groups (P = 0.1). 14.2% of hips underwent revision and 22.4% had at least one dislocation event.

No ischial fixation was associated with a higher risk of cup migration (6/13 vs. 2/36, X2 = 11.5, P = 0.0007). Cup migration was associated with an increased risk for all cause revision (4/8 vs. 3/38, X2 = 9.96, P = 0.0016, but not with dislocation (3/8 vs. 8/41, X2 = 1.2, P = 0.26).

The results suggest that failure to achieve adequate ischial fixation, with screws passing through the flange of the custom component into the ischium, increases the risk of cup migration, which, in turn, is a risk factor for revision.

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.

The role of dual consultant operating (DCO) in general orthopaedics has not been researched; where it has shown benefit in other specialties, there is a lack of information on how DCO affects the surgeons themselves. We wanted to explore the potential effects of DCO on stress, as a foundation for further research to guide support for our surgeons.

We conducted a survey among orthopaedic consultants around New Zealand, containing questions pertaining to the demographics of respondents, their experience with DCO, what the expected risks and benefits of DCO would be, and provided two high-stress exemplar clinical scenarios where respondents were asked to rate their expected stress level at baseline, with a more junior consultant present, and with a more senior consultant present.

We found 99% of respondents had been involved in DCO at some point in their careers, yet only 38% were involved in DCO on at least a monthly basis. Perceived benefits greatly outweighed potential risks: 95% felt DCO would decrease their stress, 91% felt it improved intraoperative decision making, and 89% felt it provided more enjoyment at work and enhanced collegiality. A decrease in perceived stress was seen from baseline with a more junior consultant available and a greater decrease in stress seen with a more senior consultant, particularly in a complex elective setting.

All respondents felt there is benefit in DCO and the vast majority feel it has positive effects on stress levels. In a time where burnout is more prevalent, using tools such as DCO could be an effective way to decrease stress, enhance enjoyment and collegiality — challenging some key contributors to burnout — and support mentorship with further skill acquisition. This research provides a good base to pursue further qualitative and quantitative research into the area, with a view to addressing barriers to provision of regular DCO.

Aim

Prosthetic joint infections pose a major clinical challenge. Developing novel material surface technologies for orthopedic implants that prevent bacterial adhesion and biofilm formation is essential. Antimicrobial coatings applicable to articulating implant surfaces are limited, due to the articulation mechanics inducing wear, coating degradation, and toxic particle release. Noble metals are known for their antimicrobial activity and high mechanical strength and could be a viable coating alternative for orthopaedic implants [1]. In this study, the potential of thin platinum-based metal alloy coatings was developed, characterized, and tested on cytotoxicity and antibacterial properties.

Introduction

Trochleoplasty is an effective surgical procedure for patients with severe trochlear dysplasia and recurrent patella instability. Previous work has suggested patients demonstrate early improvements in knee function and quality of life. However, concerns regarding longer term outcomes due to the development of stiffness and patellofemoral osteoarthritis remain a concern for these patients. Our aim was to assess mid-term patient-reported outcome and quality of life measures for trochleoplasty performed at a single centre for severe trochlear dysplasia.

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.

We have previously reported on the improved all-cause revision and improved revision for instability risk in lipped liner THAs using the NJR dataset. These findings corroborate studies from the Australian (AOANJRR) and New Zealand (NZOA) joint registries. The optimal orientation of the lip in THAs utilising a lipped liner remains unclear to many surgeons. The aim of this study was to identify impingement-free optimal liner orientations whilst considering femoral stem version, cup inclination and cup version.

A cementless THA kinematic model was developed using a 20 degree XLPE liner. Physiological ROM and provocative dislocation manoeuvre analyses were performed. A total of 9 cup positions were analysed (inclination 30–40–50 degrees, anteversion 5-15-25 degrees) and combined with 3 stem positions (anteversion 0-15-30 degrees) and 5 lip orientations (right hip 11 to 7 o'clock).

Some lip orientation/component position combinations lead to impingement within the physiological ROM range. Using a lipped liner increases the femoral head travel distance prior to dislocation when impingement occurs in the plane of the lip. In THAs with a cup inclination of 30 and 40 degrees, inferior lip orientations (7–8 o'clock for a right hip) performed best. Superior lip orientation performed best with a cup inclination of 50 degrees. Femoral stem version has a significant effect on the range of movement prior to impingement and hence the preferred lip orientation.

The optimal orientation of the lip in lipped liner THA is dependent on the position of both the acetabular and femoral components. In the common component orientation combination of stem anteversion 15, cup inclination 40 and cup anteversion 15, the optimal lip orientation was postero-inferiorly (8 o'clock for a right hip). Preventing impingement during physiological ROM is possible with appropriate lip liner orientation.

A larger radial tuberosity, and therefore a smaller radioulnar space, may cause mechanical impingement of the DBT predisposing to tear. We sought to investigate anatomic factors associated with partial DBT tears by retrospectively reviewing 3-T MRI scans of elbows with partial DBT tears and a normal elbow comparison group

3-T MRI scans of elbows with partial DBT tears and elbows with no known pathology were reviewed retrospectively by two independent observers. Basic demographic data were collected and measurements of radial tuberosity length, radial tuberosity thickness, radio-ulnar space, and radial tuberosity-ulnar space were made using simultaneous tracker lines and a standardised technique. The presence or absence of enthesophytes and the presence of a single or double DBT were noted.

26 3-T MRI scans of 26 elbows with partial DBT tears and 30 3-T MRI scans of 30 elbows without pathology were included. Basic demographic data was comparable between the two groups. The tear group showed statistically significant larger mean measurements for radial tuberosity length (24.3mm vs 21.3mm, p=0.002), and radial tuberosity thickness (5.5mm vs 3.7mm, p=<0.0001. The tear group also showed statistically significant smaller measurements for radio-ulnar space (8.2mm vs 10.0mm, p=0.010), and radial tuberosity-ulnar space (7.2mm vs 9.1mm, p=0.013). There was a statistically significant positive correlation between partial DBT tears and presence of enthesophytes (p=0.007) as well as between partial DBT tears and having two discrete DBTs rather than a single or interdigitating tendon (p=<0.0001).

Larger radial tuberosities, and smaller radio-ulnar and radial tuberosity-ulnar spaces are associated with partial DBT tears. This may be due to chronic impingement, tendon delamination and consequent weakness which ultimately leads to tears. Enthesophytes may be associated with tears for the same reason. Having two discrete DBTs that do not interdigitate prior to insertion is also associated with partial tears.

Abstract Background

The treatment of bone and joint infections (BJI) involving multi-drug resistant bacteria remains a challenge. MDR Staphylococcus epidermidis (MDRSE) clones, resistant to methicillin, clindamycin, levofloxacin, rifampicin and even linezolid, have been reported worldwide. The interest of delafloxacin (DFX), theoretically active on MRSA, remains to be evaluated with respect to MDRSE.

Abstract

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.

Dual mobility (DM) is most often used by surgeons to reduce instability in high risk patients. NJR data on DM has not demonstrated a reduction in all cause revision and has reported an increase in revision for peri-prosthetic fracture (PPF). The aim of our study was:

Prospective F/U of a DM implant since 2016 and enrolled into Beyond Compliance (BC). Primary outcome measure all-cause revision with secondary outcome including any re-operation and Oxford Hip Score (OHS). All patients were risk stratified and considered high risk for instability. Complications were identified via hospital records, clinical coding linkage, NJR and BC. Benchmarking data for comparison was obtained from same data sources we also considered all B type PPF that occurred with cemented polished taper stem (PTS).

159 implants in 154 patients with a mean age 74.0 years and a maximum F/U of 6.7 years. Survivorship for all-cause revision 99.4% (95% CI 96.2–99.8). One femoral only revision. Mean gain in OHS 27.4. Dislocation rate 0.6% with a single event. Patients with a PTS rate of Type B PPF 2.1% requiring revision/fixation. Compared to cTHA this cohort was significantly older (74.0 vs 68.3 years), more co-morbidity (ASA 3 46.5% vs 14.4%) and more non-OA indications (32.4% vs 8.5%). Relative risks for dislocation 0.57 (95%CI 0.08–4.1) and PPF 1.75 (95%CI 0.54–5.72). Every patient had at least one risk factor for falling and >50% of cohort had 4 or more risk factors using NICE tool.

The selective use of DM in high-risk patients can reduce the burden of instability. These individuals are very different to the “average” THA patient. A “perfect storm” is created using a high-risk implant combination (DM & PTS) in high-risk falls risk population. This re-enforces the need to consider all patient and implant factors when deciding bearing selection.

Abstract

Aim

The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality.

Tibiotalocalcaneal arthrodesis (TTCA) is a salvage procedure to functionally block the ankle and subtalar joints to treat severe ankle and hindfoot disease. Complication rates range between 20-40%, with below-knee amputation rate 1.5-19%. The heterogeneous patient cohort and indication(s) for surgery make post-operative outcomes difficult to predict. Consulting patients about potential pain and functional outcomes is difficult. When researching this area commonly, PROM data is used, less frequently functional objective measures like the 2-minute-walk-test (2MWT) are used. The aim was to compare the PROMs and objective outcomes between patients who underwent TTCA and BKA.

Fifty-two patients underwent a TTCA using an intramedullary hindfoot nail. Indications for TTCA, post-traumatic OA, failed arthrodesis and malalignment. These patients were compared to 11 patients who underwent unilateral below knee amputation (BKA) due to trauma. Outcomes measures PROMs AOFAS ankle hindfoot scale and Shor-Form 36 (SF-36). Objective measures; 2MWT, Timed-up-and-go (TUG).

Mean age TTCA 55.9, BKA 46.4. Average follow-up time 53 months. TTCA group had average 6.3 operations prior to arthrodesis (range 1-23). Of the TTCA group two ankles did not unite (7%), all complication rate 35%, 18% reported no pain. A significant negative correlation was demonstrated between the clinical outcome and the number of surgeries prior to the TTCA. TUG and 2MWT had significantly (p<0.05) better outcomes for the BKA group compared to TTCA. SF-36 BKA patients scored higher than the TTCA patients on physical functioning (p<0.01) and mental health (p<0.05) subscales as well as the mental component score (p<0.05).

This study gives clinicians evidence about the natural history of hindfoot arthrodesis and functional outcomes from BKA. Hopefully this study will improve evidence to help patients and surgeons make decisions about expected surgical outcomes from TTCA and BKA procedures.

Critical-sized bone defects can result from trauma, inflammation, and tumor resection. Such bone defects, often have irregular shapes, resulting in the need for new technologies to produce suitable implants. Bioprinting is an additive manufacturing method to create complex and individualised bone constructs, which can already include vital cells.

In this study, we established an extrusion-based printing technology to produce osteoinductive scaffolds based on polycaprolactone (PCL) combined with calcium phosphate, which is known to induce osteogenic differentiation of stem cells.

The model was created in python based on the signed distance functions. The shape of the 3D model is a ring with a diameter of 20 mm and a height of 10 mm with a spongiosa-like structure. The interconnected irregular pores have a diameter of 2 mm +/− 0.2 mm standard deviation.

Extrusion-based printing was performed using the BIO X6. To produce the bioink, PCL (80 kDa) was combined with calcium phosphate nanopowder (> 150 nm particle size) under heating. After printing, 5 × 10⁶ hMSC were seeded on the construct using a rotating incubator.

We were able to print a highly accurate ring construct with an interconnected pore structure. The PCL combined with calcium phosphate particles resulted in a precise printed construct, which corresponded to the 3D model. The bioink containing calcium phosphate nanoparticles had a higher printing accuracy compared to PCL alone. We found that hMSC cultured on the construct settled in close proximity to the calcium phosphate particles. The hMSC were vital for 22 days on the construct as demonstrated by life/dead staining.

The extrusion printing technology enables to print a mechanically stable construct with a spongiosa-like structure. The porous PCL ring could serve as an outer matrix for implants, providing the construct the stability of natural bone. To extend this technology and to improve the implant properties, a biologised inner structure will be integrated into the scaffold in the future.

The aim of this study was to investigate surgeons’ reported change of treatment preference in response to the results and conclusion from a randomized controlled trial (RCT) and to study patterns of change between subspecialties and nationalities.

Two questionnaires were developed through the Delphi process for this cross-sectional survey of surgical preference. The first questionnaire was sent out before the publication of a RCT and the second questionnaire was sent out after publication. The RCT investigated repair or non-repair of the pronator quadratus (PQ) muscle during volar locked plating of distal radial fractures (DRFs). Overall, 380 orthopaedic surgeons were invited to participate in the first questionnaire, of whom 115 replied. One hundred surgeons were invited to participate in the second questionnaire. The primary outcome was the proportion of surgeons for whom a treatment change was warranted, who then reported a change of treatment preference following the RCT. Secondary outcomes included the reasons for repair or non-repair, reasons for and against following the RCT results, and difference of preferred treatment of the PQ muscle between surgeons of different nationalities, qualifications, years of training, and number of procedures performed per year.

Of the 100 surgeons invited for the second questionnaire, 74 replied. For the primary outcome, 6 of 32 surgeons (19%), who usually repaired the PQ muscle and therefore a change of treatment preference was warranted, reported a change of treatment preference based on the RCT publication. Of the secondary outcomes, restoring anatomy was the most common response for repairing the PQ muscle.

The majority of the orthopaedic surgeons, where a change of treatment preference was warranted based on the results and conclusion of a RCT, did not report willingness to change their treatment preference.

Abstract

Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability.

In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in

sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem.

There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits.

This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.

Superior teamwork in the operating theatre is associated with improved technical performance and clinical outcomes. Yet modern rota patterns, workforce shortages, and increasing complexity of surgery, means that there is less familiarity between staff and the required choreography. Immersive Virtual Reality (iVR) can successfully train surgical staff individually, however iVR team training has yet to be investigated. We aimed to design a multiplayer iVR platform for anterior approach total hip arthroplasty (AA-THA) and assess if multiplayer iVR training was superior to single player training for acquisition of both technical and non-technical skills.

An iVR platform with choreographed roles for the surgeon and scrub nurse was developed using Cognitive Task Analysis. Forty participants were randomised to individual or team iVR training. Individually- trained participants practiced alongside virtual avatar counterparts, whilst teams trained live in pairs. Both groups underwent five iVR training sessions over 6-weeks. Subsequently, they underwent a real-life assessment in which they performed AA-THA on a high-fidelity model with real equipment in a simulated theatre. Teams performed together and individually trained participants were randomly paired up. Videos were marked by two blinded assessors recording the NOTSS, NOTECHS II and SPLINTS scores - validated technical and non-technical scores assessing surgeon and scrub nurse skills. Secondary outcomes were procedure time and number of technical errors.

Teams outperformed individually trained participants for non-technical skills in the real-world assessment (NOTSS 13.1 ± 1.5 vs 10.6 ± 1.6, p =0.002, NOTECHS-II score 51.7 ± 5.5 vs 42.3 ± 5.6, p=0.001 and SPLINTS 10 ± 1.2 vs 7.9 ± 1.6, p = 0.004). They completed the assessment 28.1% faster (27.2 minutes ± 5.5 vs 41.8 ±8.9, p<0.001), and made fewer than half the number of technical errors (10.4 ± 6.1 vs 22.6 ± 5.4, p<0.001).

Multiplayer training leads to faster surgery with fewer technical errors and the development of superior non-technical skills for anterior approach total hip arthroplasty. The convention of surgeons and nurses training separately, but undertaking real complex surgery together, can be supplanted by team training, delivered through immersive virtual reality.

Abstract

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.

To analyze the effect of tooth extraction site preservation on bone mineral density 6 months after surgery.

From 2020 to 2021, two adjacent teeth (37, 38) of the same patient were extracted at the same time, and then 37 were selected for site preservation, implanted with Bio-oss bone powder, covered with double Bio-gide membrane, reduce tension and sutured. After 6 months of self-healing, 38 was taken CBCT, and the gray value measurement tool in the software was used to measure the bone mineral density of 37 bone graft areas and 38 extraction sockets.

Bone density was high in the center of the bone graft area after the extraction site, and the density decreased in the adjacent alveolar socket, but the gray value was still higher than 38 for natural healing.

Extraction site surgery can improve bone mass and quality at the extraction site. It is good for implanting.

For clinical movement analysis, optical marker-based motion capture is the gold standard.

With the advancement of AI-driven computer vision, markerless motion capture (MMC) has emerged. Validity against the marker-based standard has only been examined for lightly-dressed subjects as required for marker placement. This pilot study investigates how different clothing affects the measurement of typical gait metrics.

Gait tests at self-selected speed (4 km/h) were performed on a treadmill (Motek Grail), captured by 9 cameras (Qualisys Miqus, 720p, f=100Hz) and analyzed by a leading MMC application (Theia, Canada). A healthy subject (female, h=164cm, m=54kg) donned clothes between trials starting from lightly dressed (LD: bicycle tight, short-sleeved shirt), adding a short skirt (SS: hip occlusion) or a midi-skirt (MS: partial knee occlusion) or street wear (SW: jeans covering ankle, long-sleeved blouse), the lattern combined with a short jacket (SWJ) or a long coat (SWC). Gait parameters (mean±SD, t=10s) calculated (left leg, mid-stance) were ankle pronation (AP-M), knee flexion (KF-M), pelvic obliquity (PO-M) and trunk lateral lean (TL-M) representing clinically common metrics, different joints and anatomic planes. Four repetitions of the base style (LD) were compared to states of increased garment coverage using the t-test (Bonferroni correction).

For most gait metrics, differences between the light dress (LD) and various clothing styles were absent (p>0.0175), small (< 2SD) or below the minimal clinically important differences (MCID). For instance, KF-M was for LD=10.5°±1.7 versus MD=12.0°±0.5 (p=0.07) despite partial knee cover. AP-M measured for LD=5.2°±0.6 versus SW=4.1°±0.7 (p<0.01) despite ankle cover-up. The difference for KF-M between LD=10.5°±1.7 versus SWL=6.0°±0.9, SW and SWJ (7.6°±1.5, p<0.01) indicates more intra-subject gait variability than clothing effect.

This study suggests that typical clothings styles only have a small clinically possibly negligible effect on common gait parameters measured with MMC. Thus, patients may not need to change clothes or be instructed to wear specific garments. In addition to avoiding marker placement, this further increases speed, ease and economy of clinical gait analysis with MMC facilitating high volume or routine application.

The prevalence of gluteal tendinopathy (GT) associated with osteoarthritis of the hip is difficult to determine as it is frequently undiagnosed or misdiagnosed as trochanteric bursitis. Its relationship to total hip arthroplasty (THA) outcomes is currently unknown. The aim of this study was to determine the incidence of GT at the time of hip arthroplasty and examine the relationship between GT and patient reported outcomes (PROMS) before and after THA.

Patients undergoing THA for primary osteoarthritis between August 2017 and August 2020 were recruited. Tendinopathy was assessed and graded at time of surgery. PROMS included the Oxford Hip Score (OHS), HOOS JR, EQ-5D, and were collected preoperatively and at one year after THA. Satisfaction with surgery was also assessed at 1 year.

797 patients met eligibility criteria and were graded as Grade 1: normal tendons (n =496, 62%), Grade 2: gluteal tendinopathy but no tear (n=222, 28%), Grade 3: partial/full thickness tears or bare trochanter (n=79, 10%). Patients with abnormal gluteal tendons were older (p=0.001), had a higher mean BMI (p=0.01), and were predominately female (p=0.001). Patients with higher grade tendinopathy had statistically significant inferior PROMS at one year, OHS score (44.1 v 42.9 v 41.3, p 0.001) HOOS JR (89.3 V 86.3 V 85.6 p 0.005). Increasing gluteal tendon grade was associated with a greater incidence of problems with mobility (p=0.001), usual activities (p=0.001) and pain (p=0.021) on EQ5D. There was a 3 times relative risk of overall dissatisfaction with THA in the presence of gluteal tears.

This study demonstrated that gluteal tendinopathy was commonly observed and associated with inferior 1-year PROMS in patients undergoing THA for OA. Increasing degree of tendinopathy was a negative prognostic factor for worse functional outcomes and patient satisfaction.

Common tendon injuries impair healing, leading to debilitation and an increased re-rupture risk. The impact of oxygen-sensing pathways on repair mechanisms, vital in regulating inflammation and fibrosis, remains unclear despite their relevance in tendon pathologies. Recent studies show that pulsed electromagnetic field (PEMF) reduce inflammation in human tendon cells (hTDCs) and in hypoxia-induced inflammation. We investigated the hypoxia's impact (1% and 2% oxygen tension) using magnetic cell sheet constructs (IL-1β-magCSs) primed with IL-1β. IL-1β-magCSs were exposed to low OT (1h, 4h,6h) in a hypoxic chamber. To confirm the role of PEMF (5Hz, 4mT, 50% duty cycle) on hypoxia modulation, IL-1β-magCSs, previously exposed to OT, were 1h-stimulated with PEMF. Our results show a significant increase in HIF- 1a and HIF-2a expression on IL-1β-magCSs after exposure to 2%-OT at all time points, compared to 1%- OT and normoxia. TNFa, IL-6, and IL-8 expression increased after 6 hours of 1%-OT exposure. PEMF stimulation of hypoxic IL-1β-magCSs led to decreased pro-inflammatory genes and increased anti-inflammatory (IL-4,IL-10) expression compared to unstimulated magCSs. IFN-g, TNF-α, and IL-6 release increased after 6 hours, regardless of %-OT, while IL-10 levels tended to rise after PEMF stimulation at 2%-OT. Also, NFkB expression was increased on IL-1β-magCSs exposed to 4 h and 6 h of 2%-OT, suggesting a link between NFkB and the production of pro-inflammatory factors. Moreover, PEMF stimulation showed a significantly decreased NFkB level in IL-1β-magCSs.

Overall, low OT enhances expression of hypoxia-associated genes and inflammatory markers in IL-1β-magCSs with the involvement of NFkB. PEMF modulates the response of magCSs, previously conditioned to hypoxia and to inflammatory triggers, favouring expression of anti-inflammatory genes and proteins, supporting PEMF impact in pro-regenerative tendon strategies.

Acknowledgements: ERC CoG MagTendon(No.772817), FCT under the Scientific Employment Stimulus-2020.01157.CEECIND. Thanks to Hospital da Prelada for providing tendon tissue samples (Portugal), and TERM

RES Hub (Norte-01-0145-FEDER-022190).

Early identification of patients at risk for impaired tendon healing and corresponding novel therapeutic approaches are urgent medical needs. This study aimed to clarify the role of CD3+ T-cells during acute Achilles tendon (AT) healing. Blood and hematoma aspirate were taken from 26 patients during AT reconstruction, and additional blood samples were obtained during clinical follow-up at 6, 26 and 52 weeks after surgery. T-cell subsets were analyzed by flow cytometry using CD3, CD4, CD8, CD11a, CD57 and CD28 antibodies. Clinical follow-up included functional tests, MRI assessments, and subjective questionnaires. In vitro, the functional behavior of patient-derived tenocytes was investigated in co-cultures with autologous unpolarized CD4+ or CD8+ T-cells, or IFNy-polarized CD8+ or IL17-polarized CD4+ Tcells (n=5-6). This included alterations in gene expression (qPCR), MMP secretion (ELISA), migration rate (scratch wound healing assay) or contractility (collagen gels). Analysis revealed that elevated CD4+ T-cell levels and reduced CD8+ T-cell levels (increased CD4/CD8 ratio) in hematoma aspirate and pre-operative blood were associated with inferior clinical outcomes regarding pain and function at 26 and 52 weeks. Increased levels of CD8+ -memory T-cell subpopulations in blood 6 weeks after surgery were associated with less tendon elongation. In vitro, tenocytes showed increased MMP1/2/3 levels and collagen III/I ratio in co-culture with unpolarized and/or IL17-polarized CD4+ T-cells compared to unpolarized CD8+ T-cells. This coincided with increased IL17 receptor expression in tenocytes co-cultured with CD4+ T-cells. Exposure of tenocytes to IL17-polarized CD4+ T-cells decreased their migration rate and increased their matrix contractility, especially compared to IFNy-polarized CD8+ T-cells. The CD4+ /CD8+ T-cell ratio could serve as prognostic marker for early identification of patients with impaired AT healing potential. Local reduction of CD4+ T-cell levels or their IL17 secretion represent a potential therapeutic approach to improve AT healing and to prevent weakening of the tendon ECM.

Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to age-related injury. Tendons have poor healing capacity and a lack of effective treatments can lead to ongoing pain, reduced function and re-injury. It is therefore important to identify the mechanisms underpinning age-related tendinous changes in order to develop more effective treatments. Our recent single cell sequencing data has shown that tendon cell populations have extensive heterogeneity and cells housed in the tendon interfascicular matrix (IFM) are preferentially affected by ageing. There is, however, a lack of established surface markers for cell populations in tendon, limiting the capacity to isolate distinct cell populations and study their contribution to age-related tendon degeneration. Here, we investigate the presence of the cell surface proteins MET proto-oncogene (MET), integrin subunit alpha 10 (ITGA10), fibroblast activation protein alpha (FAP) and platelet derived growth factor receptor alpha (PDGFRA) in the equine SDFT cell populations and their co-localisation with known markers.

Using Western blot we validated the specificity of selected antibodies in equine tissue before performing immunohistochemistry to establish the location of the respective proteins in the SDFT. We subsequently used double labelling immunofluorescence with the established mural cell marker desmin (DES) to distinguish between tenocyte and mural cell populations.

In situ, MET, ITGA10, and FAP presence was found in cells throughout the tendon whereas PDGFRA was present in cells within the IFM. Double labelling immunofluorescence with the mural cell marker DES showed lack of co-localisation between PDGFRA and DES suggesting PDGFRA is labelling an IFM cell population distinct from those associated with blood vessels.

PDGFRA is a promising target for the specific cell sorting of IFM-localised tenocytes, enabling their isolation and subsequent characterisation.

Acknowledgments: The authors acknowledge the Biotechnology and Biological Sciences Research Council (BB/W007282/1) for funding this work.

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.

Occlusal loading and muscle forces during mastication aids in assessment of dental restorations and implants and jaw implant design; however, three-dimensional bite forces cannot be measured with conventional transducers, which obstruct the native occlusion. The aim of this study was to combine accurate jaw kinematics measurements, together with subject-specific computational modelling, to estimate subject-specific occlusal loading and muscle forces during mastication.

Motion experiments were performed on one male participant (age: 39yrs, weight: 82kg) with healthy dentition. Two low-profile magnetic sensors were fixed to the participant's teeth and the two dental arches digitised using an intra-oral scanner. The participant performed ten continuous of chewing on a polyurethane rubber sample of known material properties, followed by maximal compression (clenching). This was repeated at the molars, premolars of both the left and right sides, and central incisors. Jaw motion was simultaneously recorded from the sensors, and finite element modelling used to estimate bite force. Specifically, simulations of chewing and biting were performed by driving the model using the measured kinematics, and bite force magnitude and direction quantified. Muscle forces were then evaluated using a rigid-body musculoskeletal model of the patient's jaw.

The first molars generated the largest bite forces during chewing (left: 309 N, right: 311 N) and maximum-force biting (left: 496 N, right: 495 N). The incisors generated the smallest bite forces during chewing (75 N) and maximum-force biting (114 N). The anterior temporalis and superficial masseter muscles had the largest contribution to maximum bite force, followed by the posterior temporalis and medial pterygoid muscles.

This study presents a new method for estimating dynamic occlusal loading and muscle forces during mastication. These techniques provide new knowledge of jaw biomechanics, including muscle and occlusal loading, which will be useful in surgical planning and jaw implant design.

Intramedullary nails (IMNs) are the current gold standard for treatment of long bone diaphyseal and selected metaphyseal fractures. Their design has undergone many revisions to improve fixation techniques, conform to the bone shape with appropriate anatomic fit, reduce operative time and radiation exposure, and extend the indication of the same implant for treatment of different fracture types with minimal soft tissue irritation.

The IMNs are made or either titanium alloy or stainless steel and work as load-sharing internal splints along the long bone, usually accommodating locking elements – screws and blades, often featuring angular stability and offering different configurations for multiplanar fixation – to secure secondary fracture healing with callus formation in a relative-stability environment. Bone cement augmentation of the locking elements can modulate the construct stiffness, increase the surface area at the bone-implant interface, and prevent cut-through of the locking elements.

The functional requirements of IMNs are related to maintaining fracture reduction in terms of length, alignment and rotation to enhance fracture healing. The load distribution during patient's activities is along the entire bone-nail interface, with nail length and anatomic fit being important factors to avoid stress risers.

Stratification is required to ensure that only those patients likely to benefit, receive Autologous Chondrocyte Implantation (ACI); ideally by assessing a biomarker in the blood. This study aimed to assess differences in the plasma proteome of individuals who respond well or poorly to ACI.

Isobaric tag for relative and absolute quantitation (ITRAQ) mass spectrometry and label-free proteomics analyses were performed in tandem as described previously by our group (Hulme et al., 2017; 2018; 2021) using plasma collected from ACI responders (n=10) compared with non-responders (n=10) at each stage of surgery (Stage I, cartilage harvest and Stage II, cell implantation).

iTRAQ using pooled plasma detected 16 proteins that were differentially abundant at baseline in ACI responders compared with non-responders (n=10) (≥±2.0 fold; p<0.05). Responders demonstrated a mean Lysholm (patient reported functional score from 0–100) improvement of 33±13 and non-responders a mean worsening of −13±13 points. The most pronounced plasma proteome shift was seen in response to Stage I surgery in ACI non-responders, with 48 proteins being differentially abundant between the two surgical procedures. We have previously noted this marked shift in response to initial surgery in the SF of ACI non-responders, several of these proteins were associated with the Acute Phase Response. One of these proteins, clusterin, could be confirmed in patients’ plasma using an independent immunoassay using individual samples. Label-free proteomic data from individual samples identified only cartilage acidic protein-1 (known to associate with osteoarthritis progression) to be significantly more abundant at Stage I in the plasma of non-responders.

This study indicates that proteins can be identified within the plasma that have potential use in ACI patient stratification. Further work is required to validate the findings of this discovery-phase work in larger ACI cohorts.

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.

Anterior approach total hip arthroplasty (AA-THA) has a steep learning curve, with higher complication rates in initial cases. Proper surgical case selection during the learning curve can reduce early risk. This study aims to identify patient and radiographic factors associated with AA-THA difficulty using Machine Learning (ML).

Consecutive primary AA-THA patients from two centres, operated by two expert surgeons, were enrolled (excluding patients with prior hip surgery and first 100 cases per surgeon). K- means prototype clustering – an unsupervised ML algorithm – was used with two variables - operative duration and surgical complications within 6 weeks - to cluster operations into difficult or standard groups.

Radiographic measurements (neck shaft angle, offset, LCEA, inter-teardrop distance, Tonnis grade) were measured by two independent observers. These factors, alongside patient factors (BMI, age, sex, laterality) were employed in a multivariate logistic regression analysis and used for k-means clustering. Significant continuous variables were investigated for predictive accuracy using Receiver Operator Characteristics (ROC).

Out of 328 THAs analyzed, 130 (40%) were classified as difficult and 198 (60%) as standard. Difficult group had a mean operative time of 106mins (range 99–116) with 2 complications, while standard group had a mean operative time of 77mins (range 69–86) with 0 complications. Decreasing inter-teardrop distance (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95–0.99, p = 0.03) and right-sided operations (OR 1.73, 95% CI 1.10–2.72, p = 0.02) were associated with operative difficulty. However, ROC analysis showed poor predictive accuracy for these factors alone, with area under the curve of 0.56. Inter-observer reliability was reported as excellent (ICC >0.7).

Right-sided hips (for right-hand dominant surgeons) and decreasing inter-teardrop distance were associated with case difficulty in AA-THA. These data could guide case selection during the learning phase. A larger dataset with more complications may reveal further factors.

Adult Spine Deformity (ASD) is a degenerative condition of the adult spine leading to altered spine curvatures and mechanical balance. Computational approaches, like Finite Element (FE) Models have been proposed to explore the etiology or the treatment of ASD, through biomechanical simulations. However, while the personalization of the models is a cornerstone, personalized FE models are cumbersome to generate. To cover this need, we share a virtual cohort of 16807 thoracolumbar spine FE models with different spine morphologies, presented in an online user-interface platform (SpineView). To generate these models, EOS images are used, and 3D surface spine models are reconstructed. Then, a Statistical Shape Model (SSM), is built, to further adapt a FE structured mesh template for both the bone and the soft tissues of the spine, through mesh morphing. Eventually, the SSM deformation fields allow the personalization of the mean structured FE model, leading to generate FE meshes of thoracolumbar spines with different morphologies. Models can be selectively viewed and downloaded through SpineView, according to personalized user requests of specific morphologies characterized by the geometrical parameters: Pelvic Incidence; Pelvic Tilt; Sacral Slope; Lumbar Lordosis; Global Tilt; Cobb Angle; and GAP score. Data quality is assessed using visual aids, correlation analyses, heatmaps, network graphs, Anova and t-tests, and kernel density plots to compare spinopelvic parameter distributions and identify similarities and differences. Mesh quality and ranges of motion have been assessed to evaluate the quality of the FE models. This functional repository is unique to generate virtual patient cohorts in ASD.

Acknowledgements: European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828)

There is an evolving body of evidence that demonstrates the role of epigenetic mechanisms, such as DNA-methylation in the pathogenesis of OA. This systematic review aims to summarize the current evidence of DNA methylation and its influence on the pathogenesis of OA.

A pre-defined protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases, to identify associations between DNA-methylation of articular chondrocytes and osteoarthritis. A search of Medline (Ovid), Embase, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central and Google Scholar was performed between 1st January 2015 to 31st January 2021. Data extraction was performed by two independent reviewers.

During the observation period, we identified 15 gene specific studies and 24 genome wide methylation analyses. The gene specific studies mostly focused on the expression of pro-inflammatory markers, such as IL8 and MMP13 which are overexpressed in OA chondrocytes. DNA hypomethylation in the promoter region resulted in overexpression, whereas hypermethylation was seen in non-OA chondrocytes. Others reported on the association between OA risk genes and the DNA methylation pattern close to RUNX2, which is an important OA signal. The genome wide methylation studies reported mostly on differentially methylated regions comparing OA chondrocytes and non-OA chondrocytes. Clustering of the regions identified genes that are involved in skeletal morphogenesis and development. Differentially methylated regions were seen in hip OA and knee OA chondrocytes, and even within different regions of an OA affected knee joint, differentially methylated regions were identified depending on the disease stage.

This systematic review demonstrates the growing evidence of epigenetic mechanisms, such as DNA methylation, in the pathogenesis of OA. In recent years, there has been a focus on the interplay between OA risk genes and DNA methylation changes which revealed a reactivation of genes responsible for endochondral ossification during development. These are important findings and may help to identify eventual future therapeutic targets. However, the current body of literature is mostly showing the differences in DNA methylation of OA chondrocytes and non-OA chondrocytes, but a true longitudinal analysis demonstrating the DNA methylation changes actually happening is still not available.

While high-performance ceramics like alumina and zirconia exhibit excellent wear resistance, they provide poor osseointegration capacity. As osseointegration is crucial for non-cemented joint prostheses, new techniques have been successfully developed for biofunctionalizing high-performance ceramic surfaces. Stable cell adhesion can be achieved by covalently bound specific peptides. In this study we investigate the effect of sterilization processes on organo-chemically functionalized surfaces.

To enhance the performance of alumina-toughened zirconia ceramics (ATZ), a 3-aminopropyldiisopropylethoxysilane (APDS) monolayer was applied and coupled with cyclo-RGD peptides (cRGD) by using bifunctional crosslinker bis(sulfosuccinimidyl)suberat (BS³). The samples were sterilized using e-beam or gamma-sterilization at 25 kGy, either before or after biofunctionalization with cRGD. Functionalization stability was investigated by contact angle measurements. The functionality of cRGD after sterilization was demonstrated using proliferation tests and cytotoxicity assays. Immunofluorescence staining (pFAK, Actin, DAPI) was conducted to evaluate the adhesion potential between the samples and human mesenchymal stem cells (hMSCs).

Functionalized samples before and after sterilization showed no significant difference regarding their contact angles. A proliferation test demonstrated that the cells on functionalized samples proliferate significantly more than on untreated samples before and after sterilization. hMSCs showed a significant higher proliferation on gamma sterilized samples compared to all other groups after 14 days. It was confirmed that the samples did not exhibit cytotoxic behavior before or after sterilization. Fluorescence microscopy demonstrated that both, cells on sterilized and on non-sterilized samples, expressed high levels of pFAK-Y397.

The investigated functionalization enables improved adhesion and proliferation of hMSCs and is stable against the investigated sterilization processes. This is of importance as the option of having a sterile product enables the start of the translation of this biofunctional coating towards preclinical and subsequently first-in-man applications.

Acknowledgments: We acknowledge the financial support of the Federal Ministry of Education and Research, BMBF (13GW0452A-C).

Osteoarthritis (OA) of the knee joint is a complex peripheral joint disorder with multiple risk factors. We aimed to examine the relationship between the grade of knee OA and anterior thigh length (ATL).

A total of 64 geriatric patients who had no total hip or knee replacement with a BMI of ≥30 were evaluated. Patients' OA severity was determined by two independent experts from bilateral standing knee radiographs according to the Kellgren-Lawrence (KL) grade. Joint cartilage structure was assessed using ultrasonography (US). The ATL, the gastrocnemius medialis (GC), the rectus femoris (RF) and the rectus abdominis (RA) skeletal muscle thicknesses as well as the RF cross-sectional area (CSA) were measured with US. Sarcopenia was diagnosed using the handgrip strength (HGS), 5× sit-to-stand test (5xSST) and bioelectrical impedance analysis.

The median (IQR) age of participants was 72 (65–88) years. Seventy-one per cent of the patients (n=46) were female. They were divided into the sarcopenic obese (31.3 %) and the non-sarcopenic obese (68.8%) groups. KL grade of all patients correlated negatively with the ATL (mm) and the thickness of GC (mm) (r= -0,517, p<0.001 and r= -0.456, p<0.001, respectively). In the sarcopenic obese and the non-sarcopenic obese groups, KL grade of the all patients was negatively correlated with ATL (mm) and thickness of GC (mm) (r= -0,986, p<0.001; r= -0.456, p=0.05 and r= -0,812, p=0.002; r= −0,427, p=0.006). KL grade negatively correlated with the RF thickness in the sarcopenic obese group (r= -0,928, p=0.008).

In conclusion, OA risk may decrease as the lower extremity skeletal muscle mass increases.

Acknowledgments: Feza Korkusuz MD is a member of the Turkish Academy of Sciences (TÜBA).

The incisura fibularis (IF) provides intrinsic stability to the ankle joint complex by interlocking the distal tibia and fibula. Despite a high frequency of ligamentous ankle injuries, scant attention has been given to the morphology of the IF morphology incisura fibularis in the onset and development of these lesions. Therefore, we systematically reviewed the relation between ligamentous ankle disorders and the morphometrics of the IF.

A systematic literature search was conducted on following databases: PubMed, Embase and Web of Science. Search terms consisted of ‘ankle trauma’, ‘ankle injury’, ‘ankle sprain’, ‘ankle fracture’, ‘tibiofibular’, ‘fibular notch’, ‘fibular incisura’, ‘incisura fibularis’, ‘morphometric analysis’, ‘ankle syndesmosis’, ‘syndesmotic stability’. The evaluation instrument developed by Hawker et al. was used to assess the quality of the selected studies. This protocol was performed according to the PRISMA guidelines and is registered on PROSPERO (CRD42021282862).

Nineteen studies were included and consisted of prospective cohort (n=1), retrospective comparative (n=10), and observational (n=8) study design. Comparative studies have found certain morphological characteristics in patients with ankle instability. Several studies (n=5) have correlated a shallow IF depth with a higher incidence of ankle injury. A significant difference has also been found concerning the incisura height and angle (n=3): a shorter incisura and more obtuse angle have been noted in patients with ankle sprains. The mean Hawker score was 28 out of 36 (range=24-31).

A shallower IF is associated with ligamentous ankle lesions and might be due to a lower osseous resistance against tibiofibular displacement. However, these results should be interpreted in light of moderate methodological quality and should always be correlated with clinical findings. Further prospective studies are needed to further assess the relation between the incisura morphometrics and ligamentous disorders of the ankle joint.

Keywords: ankle instability, ankle injury, incisura fibularis, fibular notch, tibiofibular morphometrics, ankle syndesmosis

Knee osteoarthritis (KOA) diagnosis is based on symptoms, assessed through questionnaires such as the WOMAC. However, the inconsistency of pain recording and the discrepancy between joint phenotype and symptoms highlight the need for objective biomarkers in KOA diagnosis. To this end, we study relationships among clinical and molecular data in a cohort of women (n=51) with Kellgren-Lawrence grade 2–3 KOA through Support Vector Machine (SVM) and a regulation network model (RNM). Clinical descriptors (i.e., pain catastrophism (CA); depression (DE); functionality (FU); joint pain (JP); rigidity (RI); sensitization (SE); synovitis (SY)) are used to classify patients. A Youden's test is performed for each classifier to determine optimal binarization thresholds for the descriptors. Thresholds are tested against patient stratification according to baseline WOMAC data from the Osteoarthritis Initiative, and the mean accuracy is 0.97. For our cohort, the data used as SVM inputs are KOA descriptors, synovial fluid (SL) proteomic measurements (n=25), and transcription factors (TF) activation obtained from RNM [2] stimulated with the SL measurements. The relative weights after classification reflect input importance. The performance of each classifier is evaluated through AUC-ROC analysis. The best classifier with clinical data is CA (AUC = 0.9), highly influenced by FU and SE, suggesting that kinesophobia is involved in pain perception. With SL input, leptin strongly influences every classifier, suggesting the importance of low-grade inflammation. When TF are used, the mean AUC is limited to 0.608, which can be related to the pleomorphic behaviour of osteoarthritic chondrocytes. Nevertheless, FU has an AUC of 0.7 with strong importance of FOXO downregulation. Though larger and longitudinal cohorts are needed, this unique combination of SVM and RNM shall help to map objectively KOA descriptors.

Acknowledgements: Catalan & Spanish governments 2020FI_b00680; STRATO-PID2021126469ob-C21-2, European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828). ICREA Academia.

Meniscus tears have been treated using partial meniscectomy to relieve pain in patients, although this leads to the onset of early osteoarthritis (OA). Cell-based therapies can help preserve the meniscus, although the presence of inflammatory cytokines compromises clinical outcomes. Anti-inflammatory drugs (e.g. celecoxib), can help to reduce pain in patients and in vitro studies suggest a beneficial effect on cytokine inhibited matrix content. Previously, we have demonstrated that the inhibitory effects of IL-1β can be countered by culture under low oxygen tension or physioxia. The present study sought to understand whether physioxia, celecoxib or combined application can counter the inhibitory effects IL-1β inhibited meniscus cells.

Human avascular and vascular meniscus cells (n =3) were isolated and expanded under 20% (hyperoxia) or 2% (physioxia) oxygen. Cells were seeded into collagen scaffolds (Geistlich, Wolhusen) and cultured for 28 days either in the presence of 0.1ng/mL IL-1β, 5µg/mL celecoxib or both under their expansion oxygen conditions. Histological (DMMB, collagen I and collagen II immunostaining), GAG content and gene expression analysis was evaluated for the scaffolds.

Under hyperoxia, meniscus cells showed a significant reduction in GAG content in the presence of IL-1β (*p < 0.05). Celecoxib alone did not significantly increase GAG content in IL-1β treated cultures. In contrast, physioxic culture showed a donor dependent increase in GAG content in control, IL-1β and celecoxib treated cultures with corresponding histological staining correlating with these results. Additionally, gene expression showed an upregulation in COL1A1, COL2A1 and ACAN and a downregulation in MMP13 and ADAMTS5 under physioxia for all experimental groups.

Physioxia alone had a stronger effect in countering the inhibitory effects of IL-1β treated meniscus cells than celecoxib under hyperoxia. Preconditioning meniscus cells under physioxia prior to implantation has the potential to improve clinical outcomes for cell-based therapies of the meniscus.

This study was proposed to evaluate the efficacy of fibrin clot augmentation in meniscal tear using inside-out meniscal repair.

A total of 35 patients with meniscus tears were operated on with inside-out meniscus repair and fibrin clot augmentation. Patients were evaluated preoperatively and postoperatively with clinical criteria, Lysholm knee scoring system, and MRI.

Out of the total 35 cases, 5 cases were lost to follow up. Clinical improvement was observed in 29 out of 30 patients (96.6%). The mean Lysholm score improved significantly from 67.63 ± 6.55 points preoperatively to 92.0 ± 2.9 points postoperatively (P < 0.05) in 2 years follow-up. Follow-up MRI in all patients revealed complete healing except in 1 case where the patient presented with recurrence of symptoms such as pain and locking which resolved with partial meniscectomy. Paraesthesia in the anterior part of the knee was observed in 2 cases. (6.6%).

We conclude that fibrin clot augmentation is a good cost-effective modality of treatment for repairable meniscus tears to preserve the meniscus and decrease the point contact pressure on the condyles which may prevent the early occurrence of osteoarthritis.

Articular cartilage (AC) and subchondral bone (SB) are intimately intertwined, forming a complex unit called the AC-SB interface. Our recent studies have shown that cartilage and bone marrow are connected by a three-dimensional network of microchannels (i.e. cartilage-bone marrow microchannel connector; CMMC), which differ microarchitecturally in number, size and morphology depending on the maturation stage of the bone and the region of the joint. However, the pathological significance of CMMC is largely unknown. Here, we quantitatively assessed how CMMC microarchitecture relates to cartilage condition and regional differences in early idiopathic osteoarthritis (OA).

Two groups of cadaveric female human femoral heads (intact cartilage vs early cartilage lesions) were identified and biopsy-based high-resolution micro-CT imaging was used. Subchondral bone (SB) thickness, CMMC number, maximum and minimum CMMC size, and CMMC morphology were quantified and compared between the two groups. The effect of joint region and cartilage condition on each dependent variable was examined.

The number and morphology of CMMCs were influenced by the region of the joint, but not by the cartilage condition. On the other hand, the minimum and maximum CMMC size was modified by both joint location and cartilage condition. The smallest CMMCs were consistently found in the load bearing region (LBR) of the joint. Compared to healthy subjects, the size of the microchannels was increased in early OA, most notably in the non-load bearing region (NLBR) and the peripheral rim (PR) of the femoral head. In addition, subchondral bone thinning was observed in early OA as a localized event associated with areas of partial chondral defect.

Our data suggest an enlargement of the SB microchannel network and a collective structural deterioration of the SB in early idiopathic OA.

A painful “dreaded black line” (DBL) has been associated with progression to complete fractures in atypical femur fractures (AFF). Adjacent sclerosis, an unrecognized radiological finding, has been observed in relation to the DBL. We document its incidence, associated features, demographics and clinical progression.

We reviewed plain radiographs of 109 incomplete AFFs between November 2006 and June 2021 for the presence of sclerosis adjacent to a DBL. Radiographs were reviewed for location of lesions, and presence of focal endosteal or periosteal thickening. We collected demographical data, type and duration of bisphosphonate therapy, and progression to fracture or need for prophylactic stabilization, with a 100% follow up of 72 months (8 – 184 months).

109 femurs in 86 patients were reviewed. Seventeen sclerotic DBLs were observed in 14 patients (3 bilateral), involving 15.6% of all femora and 29.8% of femora with DBLs. Location was mainly subtrochanteric (41.2%), proximal diaphyseal (35.3%) and mid-diaphyseal (23.5%), and were associated with endosteal or periosteal thickening. All patients were female, mostly Chinese (92.9%), with a mean age of 69 years. 12 patients (85.7%) had a history of alendronate therapy, and the remaining 2 patients had zoledronate and denosumab therapy respectively. Mean duration of bisphosphonate therapy was 62 months. 4 femora (23.5%) progressed to complete fractures that were surgically managed, whilst 6 femora (35.3%) required prophylactic fixation.

Peri-lesional sclerosis in DBL is a new radiological finding in AFFs, predominantly found in the proximal half of the femur, at times bilateral, and are always associated with endosteal or periosteal thickening. As a high proportion of patients required surgical intervention, these lesions could suggest non-union of AFFs, similar to the sclerotic margins commonly seen in fractures with non-union. The recognition of and further research into this new feature could shed more light on the pathophysiological progression of AFFs.