Adequate range of knee motion is critical for successful total knee arthroplasty. While aggressive physical therapy is an important component, manipulation may be a necessary supplement. There seems to be a lack of consensus with variable practices existing in managing stiff postoperative knees following arthroplasty. Hence we did a postal questionnaire survey to determine the current practice and trend among knee surgeons throughout the United Kingdom. A postal questionnaire was sent out to 100 knee surgeons registered with British Association of Knee Surgeons ensuring that the whole of United Kingdom was well represented. The questions among others included whether the surgeon used Manipulation Under Anaesthaesia (MUA) as an option for stiff postoperative knees; timing of MUA; use of Continuous Passive Motion (CPM) post-manipulation. We received 82 responses. 46.3% of the respondents performed MUA routinely, 42.6% sometimes, and 10.9% never. Majority (71.2%) performed MUA within 3 months of the index procedure. 67.5% routinely used CPM post-manipulation while 7.3% of the respondents applied splints or serial cast post MUA. 41.5% of the surgeons routinely used Patient Controlled Analgaesia +/− Regional blocks. Majority (54.8%) never performed open/arthroscopic debridement of fibrous tissue for adhesiolysis. Knee manipulation requires an additional anaesthetic and may result in complications such as: supracondylar femur fractures, wound dehiscence, patellar tendon avulsions, haemarthrosis, and heterotopic ossification. Moreover studies have shown that manipulation while being an important therapeutic adjunct does not increase the ultimate flexion that can be achieved which is determined by more dominant factors such as preoperative flexion and diagnosis. Manipulation should be reserved for the patient who has difficult and painful flexion in the early postoperative period

Osteoporosis is an international health and financial burden of ever increasing proportions. Current treatments limit the rate of bone resorption and reduce fracture risk, however they are often associated with significant and debilitating side effects. The most commonly used therapies also do not stimulate osteoblast activity . 1,2,3. Much current research focus is aimed at the metabolic and epigenetic pathways involved in osteoporosis. MicroRNAs have been shown to play an important role in bone homeostasis and pathophysiological conditions of the musculoskeletal system. Up-regulation of specific microRNAs has been identified in-vivo in osteoporotic patients . 4,5. It is hypothesized that modulation of specific microRNA expression may have a key role in future targeted therapies of musculoskeletal diseases. The assessment and analysis of their potential therapeutic use in Osteoporosis is of great importance, due to the burden of the disease. We have developed a 3D osteoporotic model from human bone marrow, without the use of scaffold. Magnetic nanoparticles are utilised to form spheroids, which provides a closer representation of the in-vivo environment than monolayer culture. This model will provide the basis for analysing future microRNA experiments to assess the potential up-regulation of osteoblastogenesis without cessation of osteoclast activity. The results of initial monolayer and spheroid experiments will be presented. Optimisation of the osteoporotic bone marrow culture conditions, involving response to differentiation medias, analysis of adipose and bone markers and cell migration in spheroid culture will be displayed. Quantitative and qualitative results, including fluorescence microscopy and in cell western, assessing the monolayer and spheroid cultures will be presented. The development of a pseudo osteoporosis model from healthy bone marrow will also be discussed. This model will form a basis of future work on microRNA targeting. The development of improved therapies for osteoporosis is of great significance due to the predicted rise in incidence of the disease and associated fragility fractures. Targeted therapies, such as the manipulation of microRNA expression, offer the opportunity to increase osteoblastogenesis and decrease osteoclastogenesis, potentially without the associated side effects of older, systemic therapies. We believe our 3D human bone marrow derived osteoporotic model offers the closest relation to the in-vivo environment for assessment and manipulation of microRNA expression

Background. Patients presenting to fracture clinic who have had initial management of a fracture performed by Accident and Emergency (A+E) often require further intervention to correct unacceptable position. This usually takes the form of booking a patient for a general anaesthetic to have manipulation under anaesthesia (MUA) or open surgery. Methods. Prospective data collection over a 6-month period. Included subjects were those that had initial management of a fracture performed by A+E, who went on to require re-manipulation in fracture-clinic. Manipulations were performed by trained plaster technicians using entonox analgesia followed by application of moulded cast. Radiographs were reviewed immediately post-manipulation by treating surgeon and patient managed accordingly. A retrospective review of radiograph images was performed by two doctors independently to grade the outcomes following manipulation. Results. 38 patients with 39 fractures included in study. Sites of fracture included 32 distal radius, 2 ankle, 1 spiral distal tibia and fibula, 3 metacarpal and 1 proximal phalanx of finger. 22 patients had anatomical/near-to anatomical reduction at post fracture-clinic manipulation of fracture and was the as well as definitive management (satisfactory outcome). 13 patients had a outcome 2 (minimally displaced but and satisfactory reduction of the fracture) at post fracture-clinic reduction. 12 of these were deemed acceptable went onto outcome 1 for definitive management with 1 going to outcome 2 (requiringed further manipulation). 4 patients had unsatisfactory reduction of fracture outcome 3 at post fracture-clinic reduction and all of these patients went onto outcome 3 (required surgery). Conclusions. This study supports the practice of possible primary reduction and if required, re-manipulation and cast moulding using only entonox analgesia, of selected patient cases fractures by trained plaster technicians. Without this intervention, almost all of these cases will have required an MUA or additionally Kirscher wire or open fixation. There is potential to utilise a plaster technician in A+E, reducing the need for further fracture clinic appointments, being more acceptable to patients and having a resultant cost-saving implication. Level of Evidence. Level 3

Introduction. Two randomised trials concluded cast type (above or below elbow) makes no significant difference in the re-displacement rate of paediatric forearm fractures involving the distal third of the radius. This has not, however, led to the universal use of below elbow casts. In particular we noted one trial reported significant re-displacement in 40% or more of cases, which was much higher than we would expect. To review the radiological outcomes and need for re-manipulation of paediatric distal forearm fractures treated with closed manipulation under anaesthesia in our institution, in part for subsequent comparison with published results. All forearm fractures treated at a specialist children's hospital in one year were reviewed retrospectively. Based on the methodology of one trial, we included all fractures involving the distal third of the radius, with or without an ulna fracture, which underwent closed manipulation. Outcomes were radiological alignment using existing radiographs and need for re-manipulation. Cast type was at the discretion of the treating surgeon. The radiological criteria for re-displacement were based on published methodology. 79 children underwent manipulation, 71 receiving above elbow casts and 8 below elbow casts. Radiologically 21% of injuries treated in an above elbow cast re-displaced (15/71) compared to 38% of those in below elbow plasters (3/8). In 2 cases the re-displacement was treated with re-manipulation. The preference in our institution was clearly for above elbow casts in this injury pattern. The small number of below elbow casts in our series limits any comparisons. Our rate of re-displacement using above elbow casts was half that of one of the published studies, so the existing literature is not consistent with our experience

Osteoporosis is an international health and financial burden of ever increasing proportions. Current treatments limit the rate of bone resorption and reduce fracture risk, however they are often associated with significant and debilitating side effects. The most commonly used therapies also do not stimulate osteoblast activity. Much current research focus is aimed at the metabolic and epigenetic pathways involved in osteoporosis. MicroRNAs have been shown to play an important role in bone homeostasis and pathophysiological conditions of the musculoskeletal system. Upregulation of specific microRNAs has been identified in-vivo in osteoporotic patients. It is hypothesized that modulation of specific mircoRNA expression may have a key role in future targeted therapies of musculoskeletal diseases. The assessment and analysis of their potential therapeutic use in Osteoporosis is of great importance, due to the burden of the disease.

We have developed a 3D osteoporotic model from human bone marrow, without the use of scaffold. Magnetic nanoparticles are utilised to form spheroids, which provides a closer representation of the in-vivo environment than monolayer culture. This model will provide the basis for analysing future microRNA experiments to assess the potential upregulation of osteoblastogenesis without cessation of osteoclast activity.

The results of initial monolayer and spheroid experiments will be presented. Optimisation of the osteoporotic bone marrow culture conditions, involving response to differentiation medias, analysis of adipose and bone markers and cell migration in spheroid culture will be displayed. Quantitative and qualitative results, including fluorescence microscopy and in cell western, assessing the monolayer and spheroid cultures will be presented. The development of a pseudo osteoporosis model from healthy bone marrow will also be discussed. This model will form a basis of future work on miRNA targeting.

The aim of this study was to assess the impact of Covid-19 measures on the rate of surgical site infections (SSI) and subsequent readmissions in orthopaedic patients. Retrospective, observational study in a level 1 major trauma center comparing rates of SSI in orthopaedic patients who underwent surgery prior to the Covid-19 lockdown versus that of patients who underwent surgery during the lockdown period. A total of 1151 patients were identified using electronic clinical records over two different time periods; 3 months pre Covid-19 lockdown (n=680) and 3 months during the Covid-19 lockdown (n=470). Patients were followed up for 1 year following their initial procedure. Primary outcome was readmission for SSI. Secondary outcomes were treatment received and requirement for further surgeries. The most commonly performed procedures were arthroplasty and manipulation under anaesthesia with 119 in lockdown vs 101 non-lockdown (p=0.001). The readmission rate was higher in the lockdown group with 61 (13%) vs 44 (6.5%) in the non-lockdown group (p <0.001). However, the majority were due to other surgical complications such as dislocations. Interestingly, the SSI rates were very similar with 24 (5%) in lockdown vs 28 (4%) in non-lockdown (p=0.472). Twenty patients (4.2%) required a secondary procedure for their SSI in the lockdown group vs 24 (3.5%) in non-lockdown (p=0.381). Mortality rate was similar at 44 (9.3%) in lockdown vs 61 (9.0%; p=0.836). Whilst Covid-19 precautions were associated with higher readmission rates, there was no significant difference in rate of SSI between the two groups

There is currently no commercially available and clinically successful treatment for scapholunate interosseous ligament rupture, the latter leading to the development of hand-wrist osteoarthritis. We have created a novel biodegradable implant which fixed the dissociated scaphoid and lunate bones and encourages regeneration of the ruptured native ligament. To determine if scaphoid and lunate kinematics in cadaveric specimens were maintained during robotic manipulation, when comparing the native wrist with intact ligament and when the implant was installed. Ten cadaveric experiments were performed with identical conditions, except for implant geometry that was personalised to the anatomy of each cadaveric specimen. Each cadaveric arm was mounted upright in a six degrees of freedom robot using k-wires drilled through the radius, ulna, and metacarpals. Infrared markers were attached to scaphoid, lunate, radius, and 3rd metacarpal. Cadaveric specimens were robotically manipulated through flexion-extension and ulnar-radial deviation by ±40° and ±30°, respectively. The cadaveric scaphoid and lunate kinematics were examined with 1) intact native ligament, 2) severed ligament, 3) and installed implant. Digital wrist models were generated from computed tomography scans and included implant geometry, orientation, and location. Motion data were filtered and aligned relative to neutral wrist in the digital models of each specimen using anatomical landmarks. Implant insertion points in the scaphoid and lunate over time were then calculated using digital models, marker data, and inverse kinematics. Root mean squared distance was compared between severed and implant configurations, relative to intact. Preliminary data from five cadaveric specimens indicate that the implant reduced distance between scaphoid and lunate compared to severed configuration for all but three trials. Preliminary results indicate our novel implant reduced scapho-lunate gap caused by ligament transection. Future analysis will reveal if the implant can achieve wrist kinematics similar to the native intact wrist

Stiffness is reported in up to 16% of patients after total knee replacement (TKR). 1. Treatment of stiffness after TKR remains a challenge. Manipulation under anaesthesia (MUA) accounts for between 6%-36% of readmissions following TKR. 2,3. The outcomes of MUA remain variable/unpredictable. Post-operative CPM is used as an adjuvant to MUA, potentially offering improved ROM, however, remains the subject of debate. We report a retrospective study comparing MUA with and without post-operative CPM. In our institution patients undergoing MUA to receive CPM post-operatively. Owing to the COVID-19 pandemic hospital admissions were limited. During this period MUA procedures were undertaken without CPM. Two cohorts were included: 1) MUA + post-operative CPM 2) Daycase MUA. Patients’ demographics, pre-manipulation ROM, post-MUA ROM, and ROM at final follow-up were recorded. Between 2017-2022 126 patients underwent MUA and were admitted for CPM and 42 had daycase MUA. The median Age was 66.5 and 64% were female. 57% had extension deficit (>5. o. ), 70% had flexion deficit (< 90. o. ), and 37% had both. The mean Pre-operative ROM was 72.3. o. (SD:18.3. o. ) vs. 68.5. o. (19.0. o. ), ROM at MUA was 95.5. o. (SD:20.7. o. ) vs 108.3. o. (SD:14.1. o. ) [p< 0.01], and at final follow-up 87.4. o. (SD:21.9. o. ) vs. 92.1. o. (SD:18.2. o. ) for daycase and CPM groups respectively. At final follow-up for the daycase and CPM groups respectively 10% vs. 7% improved, 29% vs. 13% maintained, and 57% vs. 79% regressed from the ROM achieved at MUA. The mean percentage of ROM gained at MUA maintained at final follow-up was 92%(SD:17) and 85%(SD:14)[p=0.03] for daycase and CPM groups respectively. There was no significant difference in ROM achieved at final follow-up despite the significantly greater improvement in ROM achieved at MUA for the CPM group. The CPM group lost a greater ROM after MUA (15% vs. 8%). We conclude that post-operative CPM does not improve ROM achieved after MUA

Abstract. Objectives. Stiffness is reported in 4%–16% of patients after having undergone total knee replacement (TKR). Limitation to range of motion (ROM) can limit a patient's ability to undertake activities of daily living with a knee flexion of 83. o. , 93. o. , and 106. o. required to walk up stairs, sit on a chair, and tie one's shoelaces respectively. The treatment of stiffness after TKR remains a challenge. Many treatment options are described for treating the stiff TKR. In addition to physiotherapy the most employed of these is manipulation under anaesthesia (MUA). MUA accounts for up to 36% of readmissions following TKR. Though frequently undertaken the outcomes of MUA remain variable and unpredictable. CPM as an adjuvant therapy to MUA remains the subject of debate. Combining the use of CPM after MUA in theory adds the potential benefits of CPM to those of MUA potentially offering greater improvements in ROM. This paper reports a retrospective study comparing patients who underwent MUA with and without post-operative CPM. Methods. Standard practice in our institution is for patients undergoing MUA for stiff TKR to receive CPM for between 12–24hours post-operatively. Owing to the COVID-19 pandemic hospital admissions were limited. During this period several MUA procedures were undertaken without subsequent inpatient CPM. We retrospectively identified two cohorts of patients treated for stiff TKR: group 1) MUA + post-operative CPM 2) Daycase MUA. All patients had undergone initial physiotherapy to try and improve their ROM prior to proceeding to MUA. In addition to patients’ demographics pre-manipulation ROM, post-MUA ROM, and ROM at final follow-up were recorded for each patient. Results. In total 168 patients who had undergone MUA between 2017–2022 were identified with a median Age of 66.5 years and 64% female. 57% had extension deficit (>5. o. ), 70% had flexion deficit (< 90. o. ), and 37% had both. 42 had daycase MUA without CPM and the remaining 126 were admitted for post-operative CPM. The mean Pre-operative ROM was 72.3. o. (SD:18.3. o. ) and 68.5. o. (19.0. o. ) for the daycase and CPM groups respectively. The mean ROM recorded at MUA was 95.5. o. (SD:20.7. o. ) and 108.3. o. (SD:14.1. o. ) [p<0.01] and at final follow-up was 87.4o (SD:21.9o) and 92.1o (SD:18.2o) for daycase and CPM groups respectively. At final follow-up for the daycase and CPM groups respectively 10% vs. 7% improved, 29% vs. 13% maintained, and 57% vs. 79% regressed from the ROM achieved at MUA. The mean percentage of ROM gained at MUA maintained at final follow-up was 92% (SD:17%) and 85% (SD:14%) [p=0.03] for daycase and CPM groups respectively. Conclusion. Overall, there was no significant difference in ROM achieved at final follow-up despite the significantly greater improvement in ROM achieved at MUA for the CPM group. Analysis of the percentage ROM gained at MUA maintained at follow up showed that most patients regressed from ROM achieved at MUA in both groups with those in the CPM only maintaining 85% as opposed to 92% in the daycase patients. It is our observation that post-operative CPM does not improve ROM achieved after MUA as compared to MUA alone. 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. Introduction. Altered mechanical loading is a contributing factor to low back pain, a condition affecting 80% of the population at some point in life. A plethora of in-vitro studies exist focusing on 6 degree of freedom (dof) testing of functional spinal units (FSU) to obtain a specimen stiffness matrix. Due to differences in the performance of test apparatus and in the technique used to manipulate raw data it is difficult to compare results from different groups. Objectives. Our primary objective was to develop a standardised technique to benchmark the performance of testing apparatus; a secondary objective was to standardise the data manipulation technique. Methods. 6 tests each at 250N and 500N preload were performed on synthetic FSU specimens using the Bath spine simulator, with a further 3 tests performed on porcine specimens. Three techniques were used to evaluate stiffness: first the slope of the entire load-displacement curve, inclusive of loading and unloading portions, was considered, secondly zonal stiffnesses were defined by dividing the load displacement curve into elastic and neutral zones, finally stiffness was calculated only for the loading portion of the elastic and neutral zone. The standard error of the residuals was used to compare results. Results. The stiffness matrix principal elements of the synthetic FSU showed repeatability of 3.2% and reflected specimen symmetry in the x and y (8% error). The stiffness calculation techniques including both loading and unloading portions of the curve were affected by hysteresis, an issue that did not arise when only the loading portion was used in calculations. Conclusions. It is recommended that testing apparatus performance is evaluated with synthetic specimens, to allow benchmarking against different set-ups. Furthermore, it is recommended that stiffness calculations are performed only on the loading part of the curve to eliminate the influence of hysteresis on the results. 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

In 2012 collagenase Clostridium histolyticum (Xiapex) was approved by the SMC for restricted use for the treatment of Dupuytren's contracture. Xiapex was approved on a case by case basis for patients with a palpable pretendinous cord, giving rise to MCPJ contracture of greater than 30 degrees. As of September 2012 we began to offer Xiapex injections to patients in Ayrshire who enquired about the injection, and met the SMC criteria. To date injections have been performed on 3 patients, in a total of 7 digits. Patients were assessed prior to injection and manipulation, with the degree of contracture recorded and DASH scores noted. Each patient then underwent a standard injection of 0.58 mg of Xiapex. 48 hours post injection each patient underwent manipulation under local anaesthetic, with contractures remeasured, pain scored using a visual analogue scale and complications noted. Each patient was then reviewed at 4 weeks post injection where the residual degree of contracture was recorded and a further DASH score completed. Mean contracture at the MCPJ prior to injection was 57° (range 34–80), and mean DASH score of 20.8 (range 16.7–24.2). Following manipulation mean residual contracture at the MCPJ measured 21° (range 18–28). The average pain score following was manipulation was rated at 1.1. Mild bruising and swelling were reported in all cases following injection, and manipulation resulted in 2 minor skin tears. At the 4 week review prolonged improvement of contracture was achieved with a mean residual contracture of 14° (range −2–40); with a significant improvement in DASH scores – mean 0.6 (range 0–1.8). Despite small numbers, we have found Xiapex injections to be a successful and well tolerated treatment for moderate Dupuytren's disease. Further follow up is required to assess the longevity of the correction and ensure the cost effectiveness of Xiapex

Background and purpose. There is on-going debate about a possible link between manipulation and stroke in patients, and a growing interest in other treatment reactions such as increased pain. Evidence about manipulation is contradictory. There is little published information about outcomes in osteopathy. We aimed to address this gap. Methods and results. A survey was sent to all UK practising osteopaths. Another survey was sent to patients recruited by osteopaths. Patients were surveyed before treatment, one day and two days after treatment and at six weeks. 1,082 (27.8%) osteopaths completed the practitioner survey. 2,057 patients, recruited from 212 osteopaths, completed questionnaires before, and directly after their treatment. 1,387 patients provided data six weeks after treatment. Between 10% and 20% of patients experienced increased symptoms/pain related to their main complaint in the days directly following treatment. This was highest for new patients. At 6 weeks, 4% of patients reported temporary disability, which they attributed to osteopathic treatment. 10% of patients reported seeking further consultation for worsening symptoms associated with osteopathic care. The comparison between those that received manipulation and those that did not suggests that manipulation was not linked to worsening outcomes. In the preceding year, 4% of osteopaths reported that they had patients who experienced a range of serious events. The most common event described was the occurrence of peripheral neurological symptoms. There were also 7 reports of stroke-like symptoms. Conclusion. Serious adverse events are rare. Transient increase in intensity of pain/symptoms is common. Conflict of interest: S Vogel, T Mars and R Froud are osteopaths. S Vogel, and T Pincus have received payment for keynote presentations by the General Osteopathic Council. M Underwood has received payment for the delivery of a keynote presentation by the British Osteopathic Association. Sources of funding: The majority of funding was provided by the General Osteopathic Council. Some additional funding was provided by the British School of Osteopathy

The management of bone defects and impaired fracture healing remains one of the most challenging clinical problems. Several treatments exist to aid in the healing of large bone defects, including biologics such as recombinant human bone morphogenetic protein-2 (BMP-2), yet all have met with limited success. Regeneration of bone requires a coordinated network of molecular signals where the local mechanical environment plays a major role in the success of the healing process. The mechanical environment itself is determined by the stiffness of the implant used to stabilize the fracture and weight-bearing, and if fixation is either too flexible or too rigid the healing might fail. The hypothesis is that the healing of large-segmental bone defects and fractures can be accelerated by the imposition of an appropriate mechanical environment. An overview of the progress made in this research area on how the amount of rhBMP-2 could be reduced and its effectiveness increased by providing an optimized mechanical environment to achieve bone union will be presented. Additionally, the latest findings of improved fracture healing through the manipulation of fixation stability introducing a potential clinical strategy to improve the healing outcome of unstable fractures, particularly for non-unions through increased stabilization, will be discussed

Onset and progression of osteoarthritis (OA) is affected by a plethora of factors, including joint injury, obesity, aging, and heredity. This multi-factorial etiology obstructs our understanding of driving molecular mechanisms, which likely comprise an interplay between systemic and local factors. Next to biomechanical factors and cytokines, the course of OA appears to be altered by microenvironmental oxidative stress: cumulative evidence now suggests a prominent participation of cell signalling mediated by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master regulator of cellular protective processes, in this process. Nrf2 activation through phosphorylation of mitogen-activated protein kinases (MAPKs) regulates Nrf2 target genes, like hemeoxygenase-1 (HO-1), superoxide dismutase 2 (SOD2), or NAD(P)H Quinone Dehydrogenase 1 (NQO1) in OA chondrocytes. Maintaining high levels of HO-1 appears to be beneficial against OA development. Experimental manipulation of putative antioxidant response element (ARE) binding sites alters the in vitro expression of key transcription factors of chondrocyte markers in promoter-reporter assays. Potentially, Nrf2 is involved in autophagy, intermediary metabolism and unfolded protein response. RNAi-mediated depletion of Nrf2 further significantly abrogated anti-inflammatory and chondroprotective effects and epigenetics link transcriptional pathways of ‘N-factors’, Nrf2 and NFATs, to micro-RNA signalling. Current findings thus reveal novel mechanisms regulating extracellular matrix synthesis by chondrocytes. A further understanding of these pathways and their regulation will lead to important novel targets to slow OA progression

Healthy bone metabolism is a tightly coupled dynamic process that relies on a balance between bone resorption (catabolism) by osteoclasts and bone formation (anabolism) by osteoblasts. Traditionally, tissue-engineering approaches for non-union fracture repair employ local anabolic therapeutic delivery strategies that target mesenchymal stem cells (MSCs) and osteoblasts to induce bone formation, however, the challenge of healing non-union defects depends on the cause of defect e.g. trauma or disease, and targeting bone formation alone is often not sufficient. Our research focuses on utilising both anabolic therapeutics, including recombinant human bone morphogenic protein (rhBMP) −2 and parathyroid hormone (PTH). (1–34). , and anti-catabolic bisphosphonates (BPs) to target bone metabolism. A major challenge with harnessing a combined dosing regimen is controlling the release of the individual therapeutics to target cells. We have developed a number of polymer-ceramic based biomaterial delivery systems, including injectable and implantable scaffolds, for the controlled release of rhBMP-2 and the BP zoledronic acid (ZA) and demonstrated their efficacy in vivo. A dual therapeutic load provided a synergistic enhancement of bone regeneration, demonstrating significantly increased bone formation and remodelling compared to anabolic therapies alone. Utilising hydroxyapatite as the ceramic phase in our scaffolds further increased bone formation, demonstrating the polymer-ceramic scaffolds to be osteoconductive in the absence of therapeutics. In addition, we have demonstrated the manipulation of bone metabolism through a specific dosing regimen of PTH. (1–34). , a therapeutic traditionally used as an anabolic, to induce bone remodelling and drive healing in BP loaded fractures. Our research to date has shown that optimising the delivery and regimen of anabolic and anti-catabolic therapeutics to control bone metabolism, augments the bone regenerative potential of these therapeutics in orthopaedic applications

Skeletal sequels of traumatisms, diseases or surgery often lead to bone defects that fail to self-repair. Although the gold standard for bone reconstruction remains the autologous bone graft (ABG), it however exhibits some drawbacks and bone substitutes developed to replace ABG are still far for having its bone regeneration capacity. Herein, we aim to assess a new injectable allogeneic bone substitute (AlloBS) for bone reconstruction. Decellularized and viro-inactivated human femoral heads were crushed then sifted to obtain cortico-spongious powders (CSP). CSP were then partly demineralized and heated, resulting in AlloBS composed of particles consisting in a mineralized core surrounded by demineralized bone matrix, engulfed in a collagen I gelatin. Calvarial defects (5mm in diameter, n=6/condition) in syngeneic Lewis1A rats were filled with CSP, AlloBS±TBM (total bone marrow), BCP (biphasic calcium phosphate)±TBM or left unfilled (control). After 7 weeks, the mineral volume/total volume (MV/TV) ratios were measured by µCT and Movat's pentachrome staining were performed on undemineralized frontal sections. The MV/TV ratios in defects filled with CSP, AlloBS or BCP were equivalent, whereas the MV/TV ratio was higher in AlloBS+TBM compared to CSP, AlloBS or BCP (p<0.01; Mann-Whitney). Histological analyses exhibited a collagen-rich matrix in all the defects, and osteoid at the surface of all implanted biomaterials. Our data indicates that AlloBS is a promising candidate for bone reconstruction, with ease of manipulation, injectability and substantial osteogenic capacity. Further experiments in larger animal models are under consideration to assess whether AlloBS may be a relevant clinical alternative to ABG

Intra-articular infusions of adipose tissue-derived stem cells (ASCs) are a promising tool for bone regenerative medicine, thanks to their multilineage differentiating ability. One major limitation of ASCs is represented by the necessity to be isolated and expanded through in vitro culture, thus a strong interest was generated by the adipose stromal vascular fraction (SVF), the non-cultured fraction of ASCs. Besides the easiness of retrieval, handling and good availability, SVF is a heterogeneous population able to differentiate in vitro into osteoblasts, chondrocytes and adipocytes, according to the different stimuli received. We investigated and compared the bone regenerative potential of SVF and ASCs, through their ability to grow on SmartBone. ®. , a composite xenohybrid bone scaffold. SVF plated on SmartBone. ®. showed better osteoinductive capabilities than ASCs. Collagen I, osteocalcin and TGF↕ markedly stained the new tissue on SmartBone. ®. ; microCT analysis indicated a progressive increase in mineralised tissue apposition by quantification of newly formed trabeculae (3391 ± 270,5 vs 1825 ± 133,4, p± 0,001); an increased secretion of soluble factors stimulating osteoblasts, as VEGF (153,5 to 1278,1 pg/ml) and endothelin 1 (0,43 to 1,47 pg/ml), was detected over time. In conclusion, the usage of SVF, whose handling doesn't require manipulation in an in vitro culture, could definitively represent a benefit for a larger use in clinical applications. Our data strongly support an innovative idea for a bone regenerative medicine based on resorbable scaffold seeded with SVF, which will improve the precision of stem cells implant and the quality of new bone formation

Osteoarthritis is characterised by the loss and damage of cartilage in synovial joints. Whilst joint replacement is the gold standard for end stage disease, repair or regenerative strategies aim to slow disease progression, maintain joint function and defer the need for joint replacement. One approach seeks to target endogenous repair after drilling or microfracture (a type of trauma induced repair) in the area of cartilage loss – connecting the defect to the underlying bone marrow niche. The rationale of this approach is that cells delivered to the defect site, from the bone marrow, will bring about cartilage repair. Bone marrow contains multipotent cells, including stem and stromal populations, of both the haematopoietic and skeletal systems. Bone marrow mesenchymal stromal cells (BMSCs) are characterised by tri-lineage differentiation (bone, cartilage and adipose tissue) and contribute to the formation of the bone marrow niche, which maintains haematopoietic stem cell quiescence. This quiescence ensures life-long haematopoiesis and the supply of mature blood cells to the haematopoietic system. In this study we investigate the interactions between haematopoietic and BMSCs (in both human and mouse cultures) specifically to understand the consequences on BMSCs during tissue repair. A murine MSC cell-line model was co-cultured with enriched fractions of primary murine haematopoietic progenitor cells isolated based on c-Kit, Sca-1, and lineage markers. Similarly, human bone marrow derived MSCs were co-cultured with primary bone marrow haematopoietic fractions isolated based on CD34, CD38 and lineage markers. Using confocal microscopy, we demonstrated that the two cell populations directly interact through cell-cell contact with haematopoietic cells located above and below the MSC monolayer. Cultures were then pushed to differentiate down the osteogenic lineage. Results indicate that MSCs co-cultured with haematopoietic cells exhibited significant inhibition of osteogenesis when analysed by functional assay of matrix mineralisation and gene expression analysis for transcripts including Runx2, Osterix and type I collagen. These data support the hypothesis that hematopoietic progenitor cells influence both the local homeostasis of the bone marrow as well as the repair potential of stromal cells. Such interactions could be important for the resolution of injury after trauma induced repair. Furthermore, manipulation of these interactions, such as the administration of haematopoietic cell stimulating agents, could be used to improve treatment outcomes

Background. Devices are frequently used to gain sufficient purchase in a bone so that the bone itself can be manipulated to move or rupture soft tissue attachments. During hip surgery, several different extraction corkscrews are available to remove the femoral head, each with a different screw design with no evidence to suggest which is most effective. Additionally during the use of corkscrew devices, often due to the low bone density, stripping of the screw threads out of the femoral head can occur prior to its extraction, thus requiring reinsertion. The aims of this project were to measure the primary pullout and reinsertional forces of five commercially available corkscrews. Methods. Polyurethane bone models covering a spectrum of osteoporotic to normal bone densities (0.08 gcm-3, 0.16 gcm-3 and 0.32 gcm-3) were used in axial tensile testing at two insertional depths to assess the maximum pullout force of these corkscrews (Zimmer, Stryker, Medacta, JRI, Depuy). Results. There are significant differences between the pullout forces produced throughout the different densities at both insertional depths; 0.08gcm-3 (p=0.002), 0.16 gcm-3 (p<0.001) and 0.32 gcm-3 (p=0.006). Reinsertional testing on all corkscrews demonstrated a reduction in the pullout force of approximately 70%, underlining the benefit of effective insertion and extraction on the first attempt. Conclusion. In all bone model densities, consistent differences in the pullout forces generated were identified. All the corkscrews generate forces greater than the estimated forces required to yield the soft tissues attached to a femoral head. Further work into optimising the corkscrew design, especially regarding the torque generated during insertion, will improve the efficacy of future corkscrew use. This information should be transferable to other situations where manipulation of a bone is needed at the temporary or permanent expense of the attached soft tissues. Level of Evidence. V: Biomechanical study

Background. Surgical management of calcaneus fractures is demanding and has a high risk of wound complications. Traditionally these fractures are managed with splinting until swelling has subsided. We describe a novel protocol for the management of displaced intra-articular calcaneus fractures utilising a temporizing external fixator and staged conversion to plate fixation through a sinus tarsi approach. The goal of this technique is to allow for earlier treatment with open reduction and internal fixation, minimise the amount of manipulation required at the time of definitive fixation and reduce the wound complication rate seen with the extensile approach. Methods. The records of patients with displaced calcaneus fractures from 2010–2014 were retrospectively reviewed. A total of 10 patients with 12 calcaneus fractures were treated with this protocol. All patients underwent ankle-spanning medial external fixation within 48 hours of injury. Patients underwent conversion to open plate fixation through a sinus tarsi approach when skin turgor had returned to normal. Time to surgery, infection rate, wound complications, radiographic alignment, and time to radiographic union were recorded. Results. The average Bohler's angle improved from 13.2 (range −2 to 34) degrees preoperatively to 34.3 (range 26 to 42) degrees postoperatively. The average time from external fixation to conversion to internal fixation was 4.8 (range 3 to 7) days. There were no immediate post-surgical complications. The average time to weight bearing was 8.5 weeks. The average time to radiographic union was 9.5 (range 8 to 12) weeks. There were no infections or wound complications at the time of last follow-up. Conclusions. Early temporizing external fixation for the acute management of displaced calcaneus fractures is a safe and effective method to reduce and stabilise the foot and may decrease the time to definitive fixation. In our series there were no complications related to the use of the external fixator. Level of Evidence. IV Retrospective case series