Introduction. Distal femur fractures around a total knee arthroplasty (TKA) are a growing problem for orthopaedic surgeons. The purpose of this study was to identify risks of reoperation for nonunion following open reduction and internal fixation of TKA periprosthetic distal femur fractures (PDFF). Method. Patients with PDFF (AO 33A-C[VB1, C1, D1], Su types 1-3) managed operatively with open reduction and internal fixation (ORIF) were retrospectively reviewed. Exclusion criteria were acute management with a distal femur replacement, less than 6 months of follow-up, and lack of injury or follow-up radiographs. The primary outcome measure was reoperation to achieve bony union. Comparisons were made between cases that did and did not require a reoperation to achieve union. Univariate analysis was used to identify factors to be analyzed in multivariate analysis to determine independent risk factors for the primary outcome. Result. A total of 77 patients met inclusion criteria. Union rate was 69/77 (89.6%). There were no differences between the groups for age, sex, BMI, comorbidities, Su classification, open injury, or mechanism of injury. Multivariate analysis identified risks for nonunion including post-operative malalignment (OR 1.41; CI 1.20-1.64; p<0.001), notching pre-operatively (OR 1.22; CI 1.04-1.42; p=0.012), presence of screws through fracture line (OR 1.28; CI 1.17-1.39; p<0.001), plate length <12 holes (OR 1.16; CI 1.02-1.33; p=0.024) and screw density greater than 0.4 (OR 2.18; CI 1.25-3.78; p=0.006). Conclusion. The reoperation rate to promote union was 10.4%. The study identified post-operative malalignment, notching pre-operatively, presence of screws through fracture line, plate length <12 holes, and proximal screw density greater than 40% as independent risk factors for nonunion

Background. The molecular mechanisms underlying non-union bone fractures largely remain elusive. Recently, spatial transcriptomics approaches for musculoskeletal tissue samples have been developed requiring direct placement of histology sections on barcoded slides. However, Formalin-Fixed-Paraffin-Embedded (FFPE) bone sections have been associated with limited RNA quality and read depth compared to soft tissue. Here, we test spatial transcriptomics workflows based on transcriptomic probe transfer to characterize molecular features discriminating non-union and union bone fractures in mice. Method. Histological sections (n=8) used for spatial transcriptomics (Visium CytAssist FFPE; 10x Genomics, n=4 on glass slides, n=4 on hydrogel-coated slides) were obtained from a fracture healing study in female 20-week-old C57BL/6J mice receiving either a femur osteotomy (0.7mm) or a segmental defect (2.4mm) (license 22/2022, Grisons CH). Sequence alignment and manual segmentation of different tissues (bone, defect region/callus, bone marrow, muscle) were performed using SpaceRanger and LoupeBrowser (10x Genomics). Differential gene expression was performed using DESeq2 (Seurat) followed by Gene-Set-Enrichment-Analysis (GSEA) of Gene Ontology (ClusterProfiler). Group comparison of quality measures was done using a Welch's t-test. Results are given as mean±standard deviation. Result. The quality measures, mean counts, and genes per spot, were significantly ~10× higher for sections on hydrogel slides (counts: 4700±1796, genes: 2389±1170) compared to glass slides (counts: 463±415, genes: 250±223). In challenging tissues like cortical bone, we reached high counts+genes in comparison to published data. Direct comparison of a non-union and union section showed a total of 432 differentially regulated genes, 538 in the defect region/callus. GSEA revealed differential regulation of pathways involved in muscle organ morphogenesis, cartilage development and endochondral ossification. Conclusions. Optimized spatial transcriptomics workflows based on transcriptomic probe transfer enable for improved read depth in musculoskeletal tissue enabling the characterization of molecular features discriminating non-union and union bone fractures. Acknowledgements. AO Foundation (AOTRAUMA), SNSF (PhD salary)

Abstract. Objectives. Clavicle fractures are common, yet debate exists regarding which patients would benefit from conservative versus operative management. Traditionally shortening greater than 2cm has been accepted as an indicator for surgery. However, clavicle length varies between individuals. In a cadaveric study clavicle shortening greater than 15% was suggested to affect outcomes. There is no clinical correlation of this in the literature. In this study we investigate outcomes following middle third clavicle fractures and the effect of percentage shortening on union rates. Methods. We identified a consecutive series of adults with primary midshaft clavicle fractures presenting to our institution from April 2015-March 2017. Clinical records and radiographs were reviewed to elicit outcomes. Time to union was measured against factors including; percentage shortening, displacement, comminution and smoking. Statistical significance was calculated. Results. 127 patients were identified, of whom 90 were managed conservatively and 37 operatively. Fractures were displaced in 86 patients (68%). Mean age was 41.7 years (range 18–89). Mean time to union for displaced fractures was longer than for undisplaced at 13.4 and 8.9 weeks respectively (p=0.0948). Displaced fractures treated operatively had mean time to union of 12.8 weeks, three weeks shorter than those managed conservatively (p=0.0470). Mean time to union for fractures with >15% shortening was 16.0 weeks, nearly double the 8.7 weeks with <15% shortening (p= 0.0241). Smokers had 8 weeks longer time to union (p=0.0082). Nonunion rate was 10% in fractures managed conservatively and 0% in those treated operatively. Complications following operative management were plate removal (13.5%), frozen shoulder (8.1%) and infection (2.9%). Conclusions. Nonunion rate is higher in fractures managed conservatively. Shortening >15% leads to significantly longer union time and should therefore be used as an indicator for surgery. Displacement and smoking also lengthen time to union and should be considered in the operative decision process. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Background. Fractures of the metatarsal bones are the most frequent fracture of the foot. Up to 70% involve the fifth metatarsal bone, of which approximately eighty percent are located proximally. Low-intensity pulsed ultrasound (LIPUS) has been shown to be a useful adjunct in the treatment of delayed fractures and non unions. However, there is no study looking at the success rate of LIPUS in fifth metatarsal fracture delayed unions. Objectives. The aim of our study was to investigate the use of LIPUS treatment for delayed union of fifth metatarsal fractures. Study Design & Methods. A retrospective review of patients who were treated with LIPUS following a delayed union of fifth metatarsal fracture was conducted over a three-year period (2013 – 2015). Delayed union was defined as lack of clinical and radiological evidence of union, bony continuity or bone reaction at the fracture site if 3 months has elapsed from the initial injury. Results. There were thirty patients (9 males, 21 females) in our cohort. The average age was 39.3 years. Type 2 fractures made up 43% of our cohort. Twenty-seven (90%) patients went on to progress to union clinically and radiologically following LIPUS treatment. Smoking (p=0.014) and size of fracture gap (p=0.045) were predictive of non-union. Conclusions. This is the first study looking at the use of LIPUS in the treatment of delayed union of fifth metatarsal fractures. We report a success rate of 90%. There is a role in the use of LIPUS in delayed union of fifth metatarsal fractures and can serve as an adjunct prior to consideration of surgery

Introduction and Objective. Nonunion is incomplete healing of fracture and fracture that lacks potential to heal without further intervention. Nonunion commonly presents with persistent pain, swelling, or instability. Those symptoms affect patient quality of life. It is known that using low intensity pulsed ultrasound (LIPUS) for fresh fractures promotes healing. However, effectiveness of LIPUS for nonunion is still controversial. If LIPUS is prove to be effective for healing nonunion, it can potentially provide an alternative to surgery. In addition, we can reduce costs by treating nonunion with LIPUS than performing revision surgery. Materials and Methods. The two authors carried out a systematic search of PubMed, Ovid MEDLINE, and the Cochrane Library. Meta-analysis of healing rate in nonunion and delayed union patients who underwent LIPUS was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) instruction method using a random effects model. Results. The initial search identified 652 articles. Of these, 541 were excluded on the basis of the title because they were either a review paper or covered an unrelated topic. The abstracts of the remaining 111 articles were examined further. That review resulted in a sample of 12 articles. We performed a meta-analysis with a random effects model using Open Meta Analyst software. The result of pooled effect size of healing rate was 73.4% (95%CI: 65.3–81.6%). Due to the fact that nonunion lacks potential to heal without further intervention, we suggest that the therapeutic effect of 73.4% from LIPUS is sufficiently effective. As far as we know, there are no trials comparing the therapeutic effectiveness of surgery and LIPUS, so it cannot be said which is more advantageous. However, the healing rate of revision surgery was reported between 68–96%; therefore, our result is within that range. Thus, if surgery is difficult due to complications, we can recommend LIPUS. Conclusions. Meta-analysis of healing rate of nonunion treated by low-intensity pulsed ultrasound is 73.4%, which suggests sufficient therapeutic effectiveness. Furthermore, we can say that LIPUS may provide an alternative treatment for nonunion patients who cannot tolerate revision surgery due to complications

Introduction. Stem cells have the capacity for self renewal and capability of differentiation into various cell lineages. Non union remains a clinically important problem in orthopaedic surgery. Method. We randomly assigned 45 patients into 3 groups. Test group: 15 patients in which mesenchymal stem cells prepared by conventional density-gradient centrifugation using ficoll-hypaque solution were injected (n=15), control A: 15 patients in which autogenous bone marrow aspirate were injected (n=15), control B: 15 patients in which neither the stem cell nor bone marrow injection given, symptomatically treated(n=15). Ultra sound and x rays were performed at follow up of 6, 12, 18, 24 weeks and comparison done. Results. Stem cell group: 12 patients out of 13 followed showed excellent results and 1 patient showed good result. Control A bone marrow injection group: 6/15 patients showed excellent results and 3 patients showed good results. Control B: only 2/15 patients showed excellent results. In fracture gap 4–5mm the stem cell group showed union in most of the patients. In control A and control B patients with same fracture gap failed to unite. Conclusion. In fracture situations, in which a manipulation or augmentation of natural healing mechanisms is needed to regenerate larger quantities of new bone Stem cells play a part. This technique of percutaneous stem cell injection provides a very safe, easy, non immunogenic, non invasive and reliable alternative to open bone grafting. This one-stage isolation procedure in comparison to the ex-vivo expansion of autologous cells from bone marrow/embryonic cells reduces the cost and infection rates related to the extra personal need and extended time required for the expansion. Summary. Stem cells have potential to enhance bone healing in non union of fractures

Clavicular hook plates have been used over the last decade in the treatment of lateral clavicular fractures with good rates of union reported throughout the literature. Fewer studies have reported the functional outcome of these patients and some have reported potential soft tissue damage post plate removal. We aimed to review the functional outcomes alongside union rates in patients treated with hook plates for lateral clavicular fractures. In this retrospective case series, 21 patients with traumatic lateral third clavicular fractures were included. 15 had Neer type II fractures, 4 Neer type III fractures, 1 patient had a Neer type I fracture and 1 radiograph was not able to be classified. All patients were treated with clavicular hook plates at the same district general hospital by five experienced surgeons between March 2010 and February 2015 adhering to the same surgical protocol. All patients had standard physiotherapy and post operative follow up. Plates were removed when radiological union was achieved in all but one patient who had the plate removed before union was achieved due to prolonged non-union. Patients were followed up post plate removal and evaluated clinically using the Oxford Shoulder Score. Their post plate radiographs were assessed by an independent radiologist and bony union documented. 21 patients were included. Mean age was 40 (range 14–63) with a male:female ratio of 17:4. Mean follow up was 5 months post injury (1–26 months). The hook plate remained in situ for a mean time of 4.3 months (2–16 months). One patient developed a post-operative wound infection treated with antibiotics, 2 patients developed adhesive capsulitis, one patient had not achieved bony union prior to hook plate removal at 16 months, however did achieve union 2 months post plate removal, two patients required revision plating. All patients achieved bony union eventually with good alignment and no displacement of the acromioclavicular joint seen on the most recent post operative radiographs. Post plate removal Oxford Shoulder Scores indicated good shoulder function with a mean score of 41.5 (maximum score possible 48 and the range of scores for our cohort was 30–47). Our data would support the use of hook plates in the treatment of lateral clavicular fractures. All patients achieved union eventually with good alignment and this was reflected in the good functional outcome scores. This study is limited in its small cohort and short-term follow up. More research is required to examine the long term consequences of hook plate surgery in a larger patient population

The aim of this randomised, controlled in vivo study in an ovine model was to investigate the effect of cylic pneumatic pressure on fracture healing. We performed a transverse osteotomy of the right radius in 37 sheep. They were randomised to a control group or a treatment group where they received cyclic loading of the osteotomy by the application of a pressure cuff around the muscles of the proximal forelimb. Sheep from both groups were killed at four or six weeks. Radiography, ultrasonography, biomechanical testing and histomorphometry were used to assess the differences between the groups. The area of periosteal callus, peak torsional strength, fracture stiffness, energy absorbed over the first 10° of torsion and histomorphometric analysis all showed that the osteotomies treated with the cyclic pneumatic pressure at four weeks were not significantly different from the control osteotomies at six weeks.

Introduction. Vascularized fibular grafting following tumor resection is an essential treatment option in limb salvage surgery. This study aimed to assess the surgical and oncological outcomes of patients treated in Denmark between 2010 and 2022. Method. We present a retrospective review of a national cohort comprising 27 patients. The indications were 13 cases of Ewing sarcoma, 12 cases of osteosarcoma, and 2 cases of giant cell tumor. The median age at surgery was 16 years (range: 2-39), and the median follow-up was 82 months (range: 12-138). Patients were analyzed overall and stratified into upper and lower extremity groups based on tumor location. Result. The primary rate of graft union was 63%, and after secondary procedures, the overall rate of graft union was 67%, with a median time to union of 13 months (range: 7-29). The reoperation rate was 74%, while the rate of limb salvage was 93%, with two patients undergoing amputation during follow-up. The 5-year overall survival rate was 81% (95% CI: 61-92). Patients with upper extremity tumors were more likely to attain graft union (92% vs. 47%, p=0.02) and less likely to undergo multiple reoperations (17% vs 60%, p=0.047) compared to patients with lower extremity tumors. Conclusion. Vascularized fibula grafting remains a valuable option in limb salvage surgery with acceptable long-term outcomes. However, especially in lower extremity cases, a low rate of graft union and multiple reoperations are to be expected

Introduction. The management of pathologic fractures (PF) following osteomyelitis (especially acute subtype) has not been widely investigated. This is challenging due to the infection-induced destructive process causing bone architecture defects. Therefore, this study aims to assess a stepwise treatment plan for the acute incidence of PF in long bone following pediatric acute Hematogenous osteomyelitis(AHO) (the most common mechanism in children). Method. This case series was conducted in a tertiary pediatric center. Patients with fracture incidence within the first 10 days after AHO diagnosis were included. Patients’ characteristics were retrospectively reviewed. Result. Nine patients (7 boys, involved bone: the femur(4), tibia(3), Radius(1), and Ulna(1)) were included, with a mean age of 52.56±66.18 months (7-216) and a follow-up time of 11.62±3.61 years (6.5-16 years). The etiology in all patients was hematological(Methicillin-resistant Staphylococcus aureus). Our stepwise treatment plan was as follows:. 1. Intravenous antibiotics until ESR<20, then oral to ESR<5. 2. Debridemnt surgery was performed if abscesses were detected. 3. Fracture type determined initial fixation: external fixation (4 patients, 2 unions) or casting (2 patients, both unions). 4. If the union was not obtained, internal fixation (with (2 patients) or without (2 patients) bone graft) was applied (all obtained union). 5. Circular external fixation was applied if the union was not obtained or leg length discrepancy occurred (1 case). A mean of 3.2 surgical procedures (1-6) was required to control the infection, and 1.4 surgical procedures (0-4) were required to obtain union. Except for one patient who died of septic shock, all other patients (88.8%) reached complete recovery (average length of hospital stay of 19.2 days (5-35).), and the union was obtained (the average union time of 17.25 months(4-36)) without long-term sequelae of osteomyelitis. Conclusion. The outcome of the stepwise plan in this study suggests that acute PF following AHO in pediatrics can be managed efficiently

Treatment of tibial osteomyelitis can be challenging and lengthy, with numerous complications possible during rehabilitation. We report on the usage of the Taylor Spatial Frame (TSF) for a large cohort of patients, and analyse factors that affect outcomes. Between 2015-2020, 51 patients were treated with TSF for osteomyelitis at a major trauma centre. Demographic, infection and treatment factors of: age, smoking status, diabetes, and BMI, acute (<6 weeks post injury) or chronic (>6 weeks) osteomyelitis, bacteria isolated, time to debridement, therapy/surgery number of TSF, time TSF was in, antibiotic treatment period, time to partial weight bear (PWB) and full weight bear (FWB) prescriptions, were collected. Outcomes of complications and time to union were obtained. Radiological union was achieved at mean 11.0 months. Mean follow up was 24.1 months. Six and three patients were further treated with fusion and amputation respectively. Mean treatment time with TSF was 12.1 months. 78% had some complications, with pin site infection, malunion, and non-union being most prevalent. Univariate factor analysis, multicollinearity diagnostics, then multivariate model construction were performed. Staphylococcus Epidermidis in bone debridement microbiology was significantly negatively associated with pin site infection (OR 0.093, 95% CI 0.011-0.828) and malunion (OR 0.698, 95% CI 0.573-0.849), and enterococcus with non-union (OR 0.775, 95% CI 0.656-0.916), during the treatment period. Time to union was significantly positively associated with time from admission to debridement (p=0.035), time TSF was in (p=0.021), presence of complications (p=0.045), bone loss complication(p=0.037), time to FWB prescription(p=0.001). We have analysed the effectiveness of TSF in the treatment of tibial osteomyelitis, and elucidated important injury, treatment and rehabilitation factors that affect outcome. The negative bacterial-complication cross associations could be due to successful eradication as culture specific antibiotics were used postoperatively. Earlier patient full weight bearing could enhance callous formation leading to faster union

Pericytes are contractile, motile cells that surround the capillary. Recent studies have shown that pericytes promoted joint fibrosis and induced subchondral bone angiogenesis, indicating the role of pericytes in osteoarthritis (OA). However, whether pericytes are involved in regulating inflammatory and catabolic response, as well as fibrotic repair of cartilage is still unclear. Here we used 2D and 3D models to investigate the communication of pericytes and chondrocytes under inflammatory osteoarthritis conditions. CD34-CD146+ pericytes were isolated and sorted from human bone marrow. Human OA chondrocytes were isolated from OA joints. In 2D studies, monolayer cultured chondrocytes were treated +/- pericyte conditioned media, +/- 1ng/ml IL1β for 24h. In 3D studies, pericytes and chondrocytes were cultured within fibrin gel in 3D polyurethane scaffolds, separately or combined for 7 days, followed by treatment of +/- IL1β for another 7 days (Fig 2A). The inflammatory response, catabolic activity and expression of fibrosis markers of chondrocytes and pericytes were measured by ELISA and/or q-rtPCR. Pericytes had weak inflammatory, catabolic and fibrotic response to IL1β (data not shown). The 2D study showed that pericyte conditioned media promoted inflammation, catabolism and fibrosis markers of chondrocytes, in the absence of IL1β treatment (Figure 1). However, study in 3D showed that coculture of chondrocytes and pericytes reduced the inflammatory and catabolic response of chondrocytes to IL1β and induced fibrosis markers in chondrocytes (Figure 2). Pericytes are involved in regulating inflammatory response, catabolic response and fibrosis of chondrocytes. The opposite results from 2D and 3D experiments indicate the variety of the regulatory role of pericytes in the interaction with chondrocytes within different culture models. The underlying mechanism is under evaluation with on-going studies. Acknowledgements. This study was funded by SINPAIN project, from European Union's Horizon Europe research and innovation programme under Grant Agreement NO. 101057778. Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them. For any figures or tables, please contact the authors directly

Introduction. The evaluation of treatment modalities for distal femur periprosthetic fractures (DFPF) post-total knee arthroplasty (TKA) has predominantly focused on functional and radiological outcomes in existing literature. This study aimed to comprehensively compare the functional and radiological efficacy of locking plate (LP) and retrograde intramedullary nail (IMN) treatments, while incorporating mortality rates. Method. Twenty patients (15 female, 5 male) with a minimum 24-month follow-up period, experiencing Lewis-Rorabeck type-2 DFPF after TKA were included. These patients underwent either LP (n=10) or IMN (n=10). The average follow-up duration was 48 months (range: 24–192). Treatment outcomes, including functional scores, alignment, union time, complications, and mortality rates, were assessed and compared between LP and IMN groups. Clinical examination findings pre-treatment and at final follow-up, along with two-way plain radiographs, were utilized. Statistical analyses comprised Student's t-test and Kaplan-Meier survival analysis with a 95% confidence interval. Result. At final follow-up, the LP group demonstrated a mean Knee Society score of 67.2 ± 16.1, while the IMN group exhibited a score of 72.8 ± 9.4(P = 0.58). No statistically significant differences were observed in alignment between the groups[aLDFA (anatomical lateral distal femoral angle), P = 0.31; aPDFA (anatomical posterior distal femoral angle), P = 0.73]. The mean time to union was 3.7 ± 0.8 months for LP and 3.9 ± 0.6 months for IMN (P = 0.62). Complications such as infection occurred in 1 LP patient, and non-union was observed in 2 LP patients, while no complications were noted in IMN group(P < 0.01). Mortality rates were notably lower in the IMN group compared to the LP group across various time intervals. Conclusion. Both LP and IMN treatments yielded similar functional scores, alignment, and union time for DFPF post-TKA. However, the lower incidence of complications and mortality rates associated with IMN treatment suggest its superiority in managing DFPF following TKA

Titanium alloys are one of the most used for orthopaedic implants and the fabrication of them by 3D printing technology is a raising technology, which could effectively resolve existing challenges. Surface modification of Ti surfaces is often necessary to improve biocorrosion resistance, especially in inflammatory conditions. Such modification can be made by coatings based on hydrogels, like alginate (Alg) - a naturally occurring anionic polymer. The properties of the hydrogel can be further enhanced with calcium phosphates like octacalcium phosphate (OCP) as a precursor of biologically formed hydroxyapatite. Formed Alg-OCP matrices have a high potential in wound healing, delivery of bioactive agents etc. but their effect on 3D printed Ti alloys performance was not well known. In this work, Alg-OCP coated 3D printed samples were studied with electrochemical measurements and revealed significant variations of corrosion resistance vs. composition of the coating. The potentiodynamic polarization test showed that the Alg-OCP-coated samples had lower corrosion current density than simple Alg-coated samples. Electrochemical impedance spectroscopy indicated that OCP incorporated hydrogels had also a high value of the Bode modulus and phase angle. Hence Alg-OCP hydrogels could be highly beneficial in protecting 3D printed Ti alloys especially when the host conditions for the implant placement are inflammatory. AcThis work was supported by the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions GA860462 (PREMUROSA). The authors also acknowledge the access to the infrastructure and expertise of the BBCE – Baltic Biomaterials Centre of Excellence (European Union Horizon 2020 programme under GA857287)

To evaluate the functional outcome of open humerus diaphyseal fractures treated with the Three-stitch technique of antegrade humerus nailing. This is a retrospective study conducted at the Department of Orthopaedics in D. Y. Patil University, School of Medicine, Navi Mumbai, India. The study included 25 patients who were operated on from January 2019 to April 2021 and follow-ups done till May 2022. Inclusion criteria were adult patients with open humerus diaphyseal fractures (Gustilo-Anderson Classification). All patients with closed fractures, skeletally immature patients, and patients with associated head injury were excluded from the study. All patients were operated on with a minimally invasive Three-stitch technique for antegrade humerus nailing. All patients were evaluated based on DASH score. Out of the 25 patients included in the study, all patients showed complete union. The mean age of the patients was 40.4 years (range 23–66 years). The average period for consolidation of fracture was 10.56 weeks (range 8–14 weeks). The DASH score ranged from 0 to 15.8 with an average score of 2.96. Five patients reported complications with three patients of post-operative infection and delayed wound healing and two patients with screw loosening. All complications were resolved with proper wound care and the complete union was noted. None of the patients had an iatrogenic neurovascular injury. Three-stitch antegrade nailing technique is a novel method to treat diaphyseal humerus fractures and provides excellent results. It has various advantages such as minimal invasiveness, minimal injury to the rotator cuff, fewer infection rates, minimal iatrogenic injuries, and good functional outcomes. Therefore, this treatment modality can be effectively used for open humerus diaphyseal fractures

Abstract. OBJECTIVES. To determine if force measured using a strain gauge in circular external fixation frames is different for 1) different simulated stages of bone healing, and for 2) fractures clinically deemed either united or un-united. METHODS. In a laboratory study, 3 similar Ilizarov frame constructs were assembled using a Perspex bone analogue. Constructs were tested in 10 different clinical situations simulating different stages of bone healing including with the bone analogue intact, with 1,3 and 50mm gaps, and with 6 materials of varying stiffness's within the 50mm gap. A Bluetooth strain gauge was inserted across the simulated fracture focus, replacing one of the 4 threaded rods used to construct the frame. Constructs were loaded to 700N using an Instron testing machine and maximum force during loading was measured by the strain gauge. Testing was repeated with the strain gauge replacing each of the 4 threaded rods in turn, with measurements being repeated 3 times, across all 3 frame constructs for all 10 simulated clinical situations (n=360). Force measurements between the situations were compared using a Kruskal-Wallis test (KW) and a post-hoc Steel test was used for multiple comparison against control (intact bone model). Additionally, a pilot study has been initiated to assess clinical efficacy of the strain gauge measurement in patients with circular frames. The strain gauge replaced the anterior rod across the fracture focus for each patient. Patients were asked to step on a weighing scale with their affected limb, and maximum weight transfer through the limb and maximal force measured in the frame were recorded. This was repeated 3 times and a mean ratio of force to weight through affected limb was calculated for each patient. The clinical situation at each measurement was designated as united or un-united by one of the senior authors for analysis. Force measurements between the situations were compared using a Wilcoxon-Mann-Whitney test. RESULTS. In the laboratory study, including all constructs with the strain gauge in all positions, a statistically significant relationship between model stability and force measured was identified (KW test for overall relationship p<0.0001). The largest force was measured in the model with a 50mm gap (median 170N, IQR 155–192, range 83–213) and the smallest in the intact bone model (median 3N, IQR 1–8, range 0–11). Multiple comparison testing found a significant difference between intact bone and all the unstable situations (p=0.002 or better). Examining initial results from our pilot clinical study, nine measurements were available in seven patients. Three of these were taken in patients with fractures yet to unite, six in patients where union has since been confirmed clinically. The median force measured was significantly greater where the fracture was not united (median 1.66 N/kg, range 1.07–1.99 vs 0.12 N/kg, range 0.05–0.73, p=0.02). CONCLUSIONS. This laboratory study demonstrates that force measurement may be different at different stages of healing, and although only limited data was available, a pilot clinical study showed a significant relationship between the force measured and clinical union of the patient's fracture. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. Objectives. Currently, the golden standard for the management of ankle fractures is open reduction and internal fixation (ORIF), a procedure which preserves joint anatomy and function. However, ORIF is associated with high risk of infection, especially in the elderly population, who tend to suffer from osteoporosis and vascular disease. Studies recommend hindfoot nailing (HFN) as a safe and efficient management alternative for this demographic. Unlike ORIF, HFN allows immediate weight-bearing, which has been linked to a lower rate of complications. This study aims to evaluate the outcomes of hindfoot nailing in ankle fractures using a case series of 43 patients. Methods. This is a retrospective study with a sample size of 43 patients, that have a mean age of 77.3 years and several medical conditions. These patients experienced ankle fractures that were treated with HFN. Data collected included injury patterns, operative complications, rate of radiological union, comorbidities and changes in mobility and housing before and after surgery. Results. Before their fracture, 62.8% of patients mobilised using a walking stick or a wheeled frame. Following surgery, 52.4% experienced decreased level of mobility. 50% of patients achieved radiological union at the time of data analysis, whereas 52.4% of patients reported a post-operative complication, most commonly soft tissue or bone infection. Conclusions. Our study has a large sample size compared to previous research. The follow-up period varies depending on patient attendance to follow-up clinical appointments. Our patient cohort exhibits significantly lower rates of radiological union, higher incidence of complications and poor post-operative functional outcomes associated with HFN. These data contradict previous studies suggesting HFN for the surgical management of ankle fractures in the elderly and frail population and demonstrate that a more thorough evaluation of HFN is needed

Introduction and Objective. Lower limb fractures are amongst the most common surgically managed orthopaedic injuries, with open reduction and internal fixation (ORIF) as the conventional method of treatment of the fibula. In recent years, dedicated intramedullary implants have emerged for fibula fixation in tandem with the move towards minimally invasive surgery in high-risk patients. This is the largest multicentre review to date with the aim of establishing the clinical outcomes following intramedullary nail (IMN) fixation of the fibula and to identify the absolute indication for fibula IMN fixation. Materials and Methods. A retrospective study of adult patients in all UK hospitals, who underwent fibula nail fixation between 01/01/2018 and 31/10/2020 was performed. Primary outcome measures included time to union, infection rate, other post-operative complications associated with the fixation and length of hospital stay. The secondary outcome measure was to identify the indication for fibula nailing. Data tabulation was performed using Microsoft Excel and analysis was performed using SPSS Version 23 (SPSS Statistics). Results. 2 Major Trauma Centres (MTCs) and 9 Trauma Units (TUs) were eligible for inclusion. 102 patients were included and 91% were classified as ankle fractures of 68% (n=69) were Weber B, 24% (n=24) Weber C and 8% (n=9) were either distal tibial fractures with an associated fibula fracture or pilon fractures. The mean age was 64 years of which 45 were male patients and 57 were female. The average BMI was 30.03kg/m. 2. and 44% of patients were ASA 3. 74% of patients had poor pre-op skin condition including swelling and open wounds. The calculated infection rate for fibula nail was 4.9% and metal-work complication rate was 4.9%. The average time to union was 13 weeks and length of inpatient stay was 15 days (SD +/− 12 days). Conclusions. MEFNO has demonstrated that fibula nail is an ideal implant in patients who have a physiologically higher risk of surgery, poor skin condition and a complex fracture pattern. The time to union, complication and infection risks are lower than that reported in literature for ankle ORIFs

The term macromolecular crowding is used to describe equilibria and kinetics of biochemical reactions and biological processes that occur via mutual volume exclusion of macromolecules in a highly crowded structureless medium. In vivo, the extracellular space is heavily crowded by a diverse range of macromolecules and thus, biological processes occur rapidly, whilst in vitro, in the absence of macromolecules, the same processes occur very slowly, if they are initiated at all (1-3). This talk will discuss the concept of macromolecular crowding, alone or in combination with other in vitro microenvironment modulators, in tendon engineering context. Acknowledgements: This work has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme, grant agreement No. 866126. This publication has emanated from research supported by grants from Science Foundation Ireland (SFI) under grant number 19/FFP/6982

Messenger RNA (mRNA) is a new class of drug that can be used to express a therapeutic protein and, in contrast to DNA, is safer and inexpensive. Among its advantages, mRNA will immediately begin to express its encoded protein in the cell cytoplasm. The protein will be expressed for a period of time, after which the mRNA is degraded. There is no risk of genetic damage, one of the concerns with plasmid DNA (pDNA) used in traditional gene therapy approaches. Nevertheless, mRNA application in tissue regeneration and regenerative medicine remains limited. In this case, mRNA must overcome its main hurdles: immunogenicity, lack of stability, and intracellular delivery. Research has been done to overcome these limitations, and the future of mRNA seems promising for tissue repair. 1,2. This keynote talk will address questions including: What are the opportunities for mRNA to improve outcomes in musculoskeletal tissue repair, in particular bone and cartilage? What are the key factors and challenges to expediting this technology to patient treatment (beyond COVID-19 vaccination)?. Acknowledgements: E.R.B thanks the cmRNAbone project funded by the European Union's Horizon 2020 research and innovation program under the grant agreement no. 874790 and the NIH R01 AR074395 from NIAMS for funding her mRNA work