Biomaterials with mechanical or biological competence are ubiquitous in musculoskeletal disorders, and understanding the inflammatory response they trigger is key to guide tissue regeneration. While macrophage role has been widely investigated, immune response is regulated by other immune cells, including neutrophils, the most abundant leukocyte in human blood. As first responders to injury, infection or material implantation, neutrophils recruit other immune cells, and therefore influence the onset and resolution of chronic inflammation, and macrophage polarization. This response depends on the physical and chemical properties of the biomaterials, among other factors. In this study we report an in vitro culture model to describe the most important neutrophil functions in relation to tissue repair. We identified neutrophil survival and death, neutrophils extracellular trap formation, release of reactive oxygen species and degranulation with cytokines release as key functions and introduced a corresponding array of assays. These tests were suitable to identify clear differences in the response by neutrophils that were cultured on material of different origin, stiffness and chemical composition. Overall, substrates from biopolymers of natural origin resulted in increased survival, less neutrophil extracellular trap formation, and more reactive oxygen species production than synthetic polymers. Within the range of mechanical properties explored (storage modulus below 5 k Pa), storage modulus of covalently crosslinked hyaluronic acid hydrogels did not significantly alter neutrophils response, whereas polyvinyl alcohol gels of matching mechanical properties displayed a response indicating increased activation. Additionally, we present the effect of material stiffness, charge, coating and culture conditions in the measured neutrophils response. Further studies are needed to correlate the neutrophil response to tissue healing. By deciphering how neutrophils initiate and modulate the immune response to material implantation, we aim at introducing new principles to design immunomodulatory biomaterials for musculoskeletal disorders. Acknowledgments. This work was supported by the AO Foundation, AO CMF, grant AOCMF-21-04S

Bone tissue is known to possess an intrinsic regeneration potential. However, in cases of major injury, trauma, and disease, bone loss is present, and the regeneration potential of the tissue is often impaired. The process of bone regeneration relies on a complex interaction of molecules. MicroRNAs (miRNA) are small, non-coding RNAs that inhibit messenger RNAs (mRNA). One miRNA can inhibit several mRNAs and one mRNA can be inhibited by several miRNAs. Functionally, miRNAs regulate the entire proteome via the local inhibition of translation. In fact, miRNA modulation has been shown to be involved in several musculoskeletal diseases. 1. In those pathologies, they modulate the transcriptional activity of mRNAs important for differentiation, tissue-specific activity, extracellular matrix production, etc. Because of their function in inhibiting translation, miRNAs are being researched in many diseases and are already being used for interventional treatment. 2. Bone tissue and its related conditions have been widely investigated up to this day. 1,3. This talk will focus on the relevancy of miRNAs to bone tissue, its homeostasis, and disease. After, examples will be given of how miRNAs can be used in bone regeneration and diseases such as osteoporosis and osteosarcoma. The use of miRNAs in both, detection and therapy will be discussed

Introduction and Objective. The use of microfragmented adipose tissue (mFAT) for the treatment of musculoskeletal disorders, especially osteoarthritis, is gaining popularity following the positive results reported in recent case series and clinical trials. The purpose of this study is to characterize mFAT in terms of structure, cell content and secretome (i.e. protein and microvescicles released as paracrine mediators), and to compare it with unprocessed lipoaspirate tissue, in order to understand the possible mechanisms of action and the benefit derived from tissue processing. Materials and Methods. Unprocessed lipoaspirate (LA) and mFAT were obtained from 7 donors. Each tissue sample was divided in four aliquots: A) fixed in formalin for histological evaluation; B) enzymatically digested to harvest cells with the exclusion of adipocytes; C) cultured for 24 hours in serum-free DMEM to harvest secretome; D) freshly frozen for proteomic evaluation. Hematoxylin and eosin staning, as well as immunohistochemistry for CD31, CD90, CD146 were performed on aliquot A. Cell count, viability, senescence and immunophenotype were assessed on aliquot B. Culture medium from aliquot C was collected and used for proteomic analysis and micro-RNA extraction and quantitation from extracellular vesicles. Aliquot D was lysed, protein were extracted and analyzed using a high-throughput proteomic approach. Results. Histological investigations showed a lower red blood cell content in mFAT with respect to LA, while the presence of blood vessels (CD31+), stromal cells (CD90) and pericytes (CD146) was similar in all samples. These results were confirmed by flow cytometry, with reduction of erythrocytes (CD235a+) by 76% and reduction of lymphocytes (CD45+) by 79% in mFAT compared to LA. Otherwise, the proportions of stromal cells, pericytes and endothelial cells in LA and mFAT remained comparable. The percentage of senescent cells resulted similar before and after tissue processing, with very low values (< 5%). The analysis of the miRNAs contained in the extracellular vesicles in culture media identified 376 miRNAs in LA secretome and 381 in mFAT secretome. A high correlation in the expression of these miRNAs within subjects (LA and mFAT of each donor) was observed (R2> 0.8), indicating that processing in mFAT does not significantly alter the portfolio of miRNAs associated with extracellular vesicles. Proteomic analysis of secretome revealed that 217 proteins significantly differ between LA and mFAT. In particular, protein associated with acute phase were less represented in mFAT secretome, while intracellular proteins were more frequent. Proteomic analysis of tissues demonstrated a reduction of protein related to extracellular matrix and of proteins closely related to peripheral blood contamination in mFAT with respect to LA. Conclusions. Taken together, these results suggest that processing of LA into mFAT allow for removal of blood elements, in terms of red blood cells, lymphocytes, acute phase and complement system proteins, and for the reduction of extracellular matrix components. Otherwise, tissue structure, cell populations, cell viability and senescence are not influenced by tissue processing. Then, microfragmentation process represents a safe and efficient method for the application of adipose tissue properties to musculoskeletal disorders, allowing for the maintenance of all the effector elements for tissue regeneration while removing possible detrimental agents such as inflammatory mediators

Distal arthrogryposis (DA) is a collection of rare developmental disorders characterized by congenital joint contractures. Most arthrogryposis mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal tissues. However, gain-of-function (GOF) mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 via unknown mechanisms. We show that expression of a GOF PIEZO2 mutation in proprioceptive sensory neurons mainly innervating muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects via increased activity within the peripheral nervous system during postnatal development. Surprisingly, overactive PIEZO2 is likely to cause joint abnormalities via increased exocytosis from sensory neuron endings without involving motor circuitry. This reveals a role for somatosensory neurons: excessive mechanosensation within these neurons disrupts musculoskeletal development. We also present proof-of-concept that Botox injection or dietary treatment can counteract the effect of overactive PIEZO2 function to evade DA-like phenotypes in mice when applied during a developmental critical period. These approaches might have clinical applications. Beyond this, our findings call attention to the importance of considering sensory mechanotransduction when diagnosing and treating other musculoskeletal disorders. Acknowledgements: Our work is supported by National Institutes of Health grant (R35 NS105067, R01 DE022358, R25 SC3GM127195, R25 GM07138, R01GM133845, intramural) and Howard Hughes Medical Institute

The presentation of musculoskeletal disease differs in men and women, and recognition of the differences between men and women's burden of disease and response to treatment is critical to optimizing care. In this presentation, I will discuss the expanding evidence in the literature that examine the role of sex and gender in musculoskeletal disease, including how its examination increases the innovations and contributions, as well as expands the knowledge about musculoskeletal disease, conditions, and injury in a broad sense. We will discuss the role that structural anatomy differences, hormones, and genetics play in differential disease expression, to the historical biases in the subject populations of clinical and basic research projects. Participants will be provided with examples and opportunities to evaluate orthopaedic science through a sex and gender lens, and what impact this may play in setting the stage for both clinical practice and scientific investigation

Intervertebral disc (IVD) degeneration is responsible for severe clinical symptoms including chronic back pain. Galectins are a family of carbohydrate-binding proteins, some of which can induce functional disease markers in IVD cells and other musculoskeletal diseases. Galectins −4 and −8 were shown to trigger disease-promoting activity in chondrocytes but their effects on IVD cells have not been investigated yet. This study elucidates the role of galectin-4 and −8 in IVD degeneration. Immunohistochemical evidence for the presence of galectin-4 and −8 in the IVD was comparatively provided in specimens of 36 patients with spondylochondrosis, spondylolisthesis, or spinal deformity. Confocal microscopy revealed co-localization of galectin-4 and −8 in chondrocyte clusters of degenerated cartilage. The immunohistochemical presence of galectin-4 correlated with histopathological and clinical degeneration scores of patients, whereas galectin-8 did not show significant correlations. The specimens were separated into annulus fibrosus (AF), nucleus pulposus (NP) and endplate, which was confirmed histologically. Separate cell cultures of AF and NP (n=20) were established and characterized using cell type-specific markers. Potential binding sites for galectins including sialylated N-glycans and LacdiNAc structures were determined in AF and NP cells using LC/ESI-MS-MS. To assess galectin functions, cell cultures were treated with recombinant galectin-4 or −8, in comparison to IL-1β, and analyzed using RT-qPCR and In-cell Western blot. In vitro, both galectins triggered the induction of functional disease markers (CXCL8 and MMP3) on mRNA level and activated the nuclear factor-kB pathway. NP cells were significantly more responsive to galectin-8 and Il-1β than AF cells. Phosphorylation of p-65 was time-dependently induced by both galectins in both cell types to a comparable extent. Taken together, this study provides evidence for a functional role of glycobiological processes in IVD degeneration and highlights galectin-4 and −8 as regulators of pro-inflammatory and degrative processes in AF and NP cells

It is known that the gait dynamics of elderly substantially differs from that of young people. However, it has not been well studied how this age-related gait dynamics affects the knee biomechanics, e.g., cartilage mechanical response. In this study, we investigated how aging affects knee biomechanics in a female population using subject-specific computational models. Two female subjects (ages of 23 and 69) with no musculoskeletal disorders were recruited. Korea National Institute for Bioethics Policy Review Board approved the study. Participants walked at a self-selected speed (SWS), 110% of SWS, and 120% of SWS on 10 m flat ground. Three-dimensional marker trajectories and ground reaction forces (Motion Analysis, USA), and lower limbs’ muscle activities were measured (EMG, Noraxon USA). Knee cartilage and menisci geometries were obtained from subjects’ magnetic resonance images (3T, GE Health Care). An EMG-assisted musculoskeletal finite element modeling workflow was used to estimate knee cartilage tissue mechanics in walking trials. Knee cartilage and menisci were modeled using a transversely isotropic poroviscoelastic material model. Walking speed in SWS, 110%, and 120% of SWS were 1.38 m/s, 1.51 m/s, and 1.65 m/s for the young, and 1.21 m/s, 1.34 m/s and 1.46 m/s for the elderly, respectively. The maximum tensile stress in the elderly tibial cartilage was ~25%, ~33%, and ~32% lower than the young at SWS, 110%, and 120% of SWS, respectively. These preliminary results suggest that the cartilage in the elderly may not have enough stimulation even at 20% increases in walking speed, which may be one reason for tissue degeneration. To enhance these findings, further study with more subjects and different genders will investigate how age-related gait dynamics affects knee biomechanics. Acknowledgments: Australian NHMRC Ideas Grant (APP2001734), KITECH (JE220006)

Tendinopathy is the most frequent musculoskeletal disease that requires medical attention. Mechanical overload has been considered as a key driver of its pathology. However, the underline mechanism on how overload induces tendinopathy and inflammation is unclear. Extracellular mitochondria (EM) are newly identified as cell-to-cell communicators. The aim of this study is to elucidate the role of mitochondria in overload-induced inflammation. We performed three-dimensional uniaxial stretching to mouse tendon organoid in bioreactors. Cyclic strain of uniaxial loadings included underload, normal load, and overload, according to previous work. We then harvested microvesicles including EM, from the bioreactor by differential centrifugation and evaluated their characteristics by flow cytometry and super-resolution confocal microscopy. Raw 264.7 mouse macrophage cell line was used for chemotaxis assay in a Boyden Chamber System with Magnetic-Activated Cell Sorting Technology. EM induced cytokines secretion by macrophages was analyzed by a bead-based multiplex assay panel. N-Acetyl-L-cysteine (NAC) was used as the antioxidant to tendon organoid to regulate mitochondrial fitness. We showed mechanical load induced tendon organoid to release microvesicles including mitochondria. The size of microvesicles is mainly in the range from 220nm to 880nm. More than 75% of microvesicles could be stained by PKH26, confirming they were with lipophilic membrane. Super-resolution confocal microscopy identified two forms of mitochondria, including mitochondria encapsulated in vesicles and free mitochondria. Overload led to the degeneration of the organoid and induced microvesicles release containing most EM. Chemotaxis assay showed that EM from overloaded tendon organoid induced macrophages chemotaxis. In addition, microvesicles extracted from overloaded tendon organoid induced the production of proinflammatory cytokines including IL-6, KC (Keratinocyte-Derived Chemokine) and IL-18. NAC treatment to tendon cells could attenuate overload-induced macrophage chemotaxis. Overload induces EM releasing from tendon cells, which leads to chemotaxis of macrophages toward tendon, resulting in induction of inflammation

Stem cells represent an exciting biological therapy for the management of many musculoskeletal tissues that suffer degenerative disease and/or where the reparative process results in non-functional tissue (‘failed healing’). The original hypothesis was that implanted cells would differentiate into the target tissue cell type and synthesise new matrix. However, this has been little evidence that this happens in live animals compared to the laboratory, and more recent theories have focussed on the immunomodulatory effects via the release of paracrine factors that can still improve the outcome, especially since inflammation is now considered one of the central processes that drive poor tendon healing. Because of the initial ‘soft’ regulatory environment for the use of stem cells in domestic mammals, bone and fat-derived stem cells quickly established themselves as a useful treatment for naturally occurring musculoskeletal diseases in the horse more than 20 years ago (Smith, Korda et al. 2003). Since the tendinopathy in the horse has many similarities to human tendinopathy, we propose that the following challenges and, the lessons learnt, in this journey are highly relevant to the development of stem cells therapies for human tendinopathy:. Source – while MSCs can be recovered from many tissues, the predominant sources for autologous MSCs have been bone and fat. Other sources, including blood, amnion, synovium, and dental pulp have also been commercialised for allogenic treatments. Preparation – ex vivo culture requires transport from a licensed laboratory while ‘minimally manipulated’ preparations can be prepared patient-side. Cells also need a vehicle for transport and implantation. Delivery – transport of cells from the laboratory to the clinic for autologous ex vivo culture techniques; implantation technique (usually by ultrasound-guided injection to minimise damage to the cells (or, more rarely, incorporated into a scaffold). They can also be delivered by regional perfusion via venous or arterial routes. Retention – relatively poor although small numbers of cells do survive for at least 5 months. Immediate loss to the lungs if the cells are administered via vascular routes. Synovially administered cells do not engraft into tendon. Adverse effects – very safe although needle tracts often visible (but do not seen to adversely affect the outcome). Allogenic cells require careful characterisation for MHC Class II antigens to avoid anaphylaxis or reduced efficacy. Appropriate injuries to treat – requires a contained lesion when administered via intra-lesional injection. Intrasynovial tendon lesions are more often associated with surface defects and are therefore less appropriate for treatment. Earlier treatment appears to be more effective than delayed, when implantation by injection is more challenging. Efficacy - beneficial effects shown at both tissue and whole animal (clinical outcome) level in naturally-occurring equine tendinopathy using bone marrow-derived autologous MSCs Recent (licenced) allogenic MSC treatment has shown equivalent efficacy while intra-synovial administration of MSCs is ineffective for open intra-synovial tendon lesions. Regulatory hurdles – these have been lighter for veterinary treatments which has facilitated their development. There has been greater regulation of commercial allogenic MSC preparations which have required EMA marketing authorisation

Introduction. Orthopaedic trauma surgery is characterised by repetitive, forceful tasks that are physically demanding, thus theoretically increasing the risk of musculoskeletal injuries in these surgeons. The aim of this study is to assess prevalence, characteristics and impact of musculoskeletal disorders among orthopaedic trauma surgeons. Methods. A modified version of the physical discomfort survey was sent to surgeon members of the Orthopaedics Trauma Association (OTA) via e-mail. For data analysis, one-way ANOVA and Fisher Exact test were performed to compare the variables where appropriate. P values<0.05 were considered statistically significant. Results. A total of 86 surgeons completed the survey during the period of data collection. Of the respondents 84.9% were males and more than half were aged between 30–45 years old. The majority of musculoskeletal complaints and disorders were low back pain (29.3%), wrist or forearm tendinitis (18.0%), elbow lateral epicondylitis (15.4%), plantar fasciitis (14.7%). When data was analysed according to number of years in practice the results yielded a significant difference between the groups in both number of regions involved (p<0.05) and number of musculoskeletal disorders (p<0.05), as a higher proportion of these were documented in surgeons practicing for 16–20 years and more than 30 years. Also surgeons working in a private setting (p<0.005), surgeons working in more than one institute (p<0.005), increased number of regions involved (p<0.001) and increased number of musculoskeletal disorders (p<0.001) were significantly more likely to require time-off work. Conclusion. To our knowledge, our study is the first of its kind that shows a high percentage of orthopaedic trauma surgeons sustain occupational injuries some time in their careers. Cost of management and rehabilitation of these injuries, in addition to the amount of missed workdays due to these injuries indicate that these injuries have a significant economic burden on the health-care system

Musculoskeletal diseases are leading causes of disability, morbidity and economic loss across the globe today. Yet for much of the world's population access to cheap, safe and effective intervention is lacking, while others choose not to accept best practice and best evidence, or significantly more expensive treatment. Great advances have been made in some diseases like rheumatoid arthritis, but the cost of many new treatments is unaffordable, and individuals, insurance and governments struggle to, or cannot fund it. Anchor bias and politics determines national policies and research funding, often favouring other illnesses while musculoskeletal disorders lack the support proportional to their frequency and impact. This is not appreciated by policy makers and governments, and the consequences of lack of care or poor-quality care. The need has never been greater for a treatment for osteoarthritis, the most common disease in the world; but the search for a cure needs funding, and if discovered, who will pay for it?

The future of work brings several challenges and opportunities for occupational health and safety on three major drivers: the rapid progress of technological innovation; demographic changes, in particular ageing of the workforce and migration; and changes in the labour market, especially owing to new ways of per-forming jobs. Innovation technologies are leading to an overall transformation of industrial processes that offer huge developmental perspectives in the world of work and opportunities for society. In the field of prevention of musculoskeletal disorders, relevant progresses have been made in the clinical setting and in the context of care, also in relation to the ageing society. In the near future, the adaptation of workstations and the implementation of sensors and enabling technologies (collaborative robots and exoskeletons) will offer, together with the innovations in the clinic and orthopaedic surgery, a significant contribution to the reduction of risks from biomechanical overload, as well as support interventions to increase work ability and reduce the impact of disability. However, the potential risk scenarios for health and safety in the workplace, along with the progress in occupational health research, lead to the need for creating an inte-grated system of skills and approaches to adopt a Prevention through Design perspective. This requires designing and conceiving processes taking into consideration occupational risk prevention and guarantee-ing the return to work in a multidisciplinary and integrated perspective

Geriatric syndromes could lead individuals to exhibit significant mobility and psychological deficits resulting in significant healthcare costs. Thus, identifying strategies to delay aging, or prevent progressive loss of tissue homeostasis could dramatically restore the function and independence of millions of elderly patients and significantly improve quality of life. One of the fundamental properties of aging is the accumulation of senescent cells and senescence associated secretory phenotypes (SASPs) that needs to be treated in wide range of therapeutics including orthobiologics. Senolytic compounds selectively target and kill senescent cells and inhibit anti-apoptotic pathways that are upregulated in senescent cells thereby inducing apoptotic cell death and abrogating systemic SASP factors. We have also shown that blocking fibrosis with Losartan (TGF-β1 blocker) can improve musculoskeletal healing and cartilage repair by reducing the amount of fibrosis. Thus, we hypothesize that administration of anti-fibrotic agents will enhance the beneficial effects of orthobiologics. The safety and efficacy of several senolytic and anti-fibrotic agents to delay age-related dysfunction and improve the function of orthobiologics have been demonstrated in a variety of animal models (in vivo). Overall, our innovative approaches target senescent cells (inflammation) and TGF-β1 (fibrosis) to enhance the clinical efficacy and use of orthobiologics for musculoskeletal repair. We will also discuss ongoing active clinical trials on orthobiologics to aiming at evaluating the safety and efficacy of senolytic agent (Fisetin) and anti-fibrotic agent (Losartan), used independently or in combination, to enhance the beneficial effects of orthobiologics for patients afflicted with musculoskeletal diseases and conditions

Abstract. Objective. Articular cartilage damaged through trauma or disease has a limited ability to repair. Untreated, these focal lesions progress to generalized changes including osteoarthritis. Musculoskeletal disorders including osteoarthritis are the most significant contributor to disability globally. There is increasing interest in the use of mesenchymal stem cells (MSCs) for the treatment of focal chondral lesions. There is some evidence to suggest that the tissue type from which MSCs are harvested play a role in determining their ability to regenerate cartilage in vitro and in vivo. In humans, MSCs derived from synovial tissue may have superior chondrogenic potential. Methods. We carried out a systematic literature review on the effectiveness of synovium-derived MSCs (sMSCs) in cartilage regeneration in in vivo studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Nineteen studies were included in our review; four examined the use of human sMSCs and the remainder were conducted using sMSCs harvested from animals. Results. Despite the variability of animals, cell harvesting techniques, methods of delivery, and outcome measures, all studies reported successful cartilage repair with sMSC transplantation. Conclusion. We conclude that sMSC transplantation holds promise as a treatment option for focal cartilage defects. We believe that defining the cell population being used, establishing standardized methods for MSC delivery, and the use of objective outcome measures should enable future high-quality studies such as randomized controlled clinical trials to provide the evidence needed to manage chondral lesions optimally. 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

Recent clinical studies on targeting nerve growth factor (NGF) in chronic low back pain and knee osteoarthritis have demonstrated efficient pain reduction in a short-term treatment regimen. However, the increased risk for the development of rapid progressive osteoarthritis at the required high drug dose remains a serious concern and prompts thorough analysis of the tissue distribution and role of NGF in degenerative musculoskeletal disorders. Here, we sought to investigate tissue distribution of NGF, its high affinity receptor TrkA and CD68-positive macrophages in human facet joint osteoarthritis of the lumbar spine. Facet joint specimens (n=10) were harvested by facetectomy from patients undergoing elective lumbar intervertebral spine fusion. Facet joint osteoarthritis and presence of synovitis was graded using preoperative magnetic resonance imaging. Tissue distribution of NGF, TrkA and CD68 was determined using immunohistochemistry. Tissue degradation was graded on safranin-O-stained tissue sections. Association between imaging parameters and tissue distribution was determined using Pearson correlation analysis. Synovitis was present in 6 cases and facet joints displayed moderate to severe radiological osteoarthritis (median Weishaupt grade; 2 [1.5–3]). NGF was expressed in 8 of 10 specimens. NGF was expressed in connective tissue, articular and fibrocartilage, but not bone tissue. Cartilaginous NGF expression was predominantly found in the extracellular matrix of superficial cartilage tissue with complete loss of proteoglycans, chondrocyte death and structural damage (fissures). Loss of cartilage proteoglycan staining alone did not display NGF immunoreactivitiy. NGF expression was not correlated with radiological osteoarthritis severity or presence of synovitis. NGF high affinity receptor TrkA was exclusively expressed in bone marrow tissues. Differential grades of bone marrow infiltration by CD68-positive macrophages were observed, yet these were not associated with NGF expression. Targeting NGF in chronic low back pain and/or facet joint osteoarthritis might affect pathomechanisms in cartilaginous tissues and NGF signalling in the bone marrow compartment

Musculoskeletal disorders is one of most important health problems human population is facing includes. Approximately 310 thousand of hip protheses have been used in 45 years and older patients in total according to the recent studies have been done. [1, 2]. Many factors, including poor osseointegration or relaxation of the implant due to stress, limit the life of the load-bearing implants [3]. To overcome these difficulties and to protect metal implants inside the body, the surfaces of the implants were coated with silver ion doped hydroxyapatite/bioglass. In this study, silver doped hydroxyapatite ceramic powder and 6P57 bioglass were synthesized. Two different coating suspensions, 100% bioglass and 70% Ag-HAp / 30% bioglass, were prepared in methyl alcohol with a solid content of 1% by weight. Two layers were coated on the external fixator nails by using electrospray method with the bioglass and Ag-Hap/Bioglass suspensions respectively. The coated implants were cut with an equal surface area and kept in human blood plasma for different time. The scanning electron microscopy (SEM, Zeiss Supra 50VP and Zeiss Evo 50EP) and stereo microscope (Zeiss Axiocam Stemi 2000-C) were used to characterize microstructure and thickness of coated surface. Energy dispersive X-ray Spectroscopy was used characterized of chemical composition of coating. Changing of pH value of plasma was measured by pH meter (Hanna HI83414). In addition, the ICP method was used to determine the elements contained in the plasma fluid after dissolution. As a result of this study, physical and chemical changes occurring on the coating surface in different time periods are presented in detail

Abstract. Objectives. The purpose of this study was to determine the cost of inpatient admissions for developmental dysplasia of the hip (DDH) at a UK tertiary referral centre, and identify any association between newborn screening (NIPE) status and the cost of treatment. Methods. This was a retrospective study, using hospital episodes data from a single NHS trust. All inpatient episodes between 01/01/2014 to 30/06/2019 with an ICD-10 code stem of Q65 ‘congenital deformities of hip’ were screened to identify admissions for management of DDH. Data was subsequently obtained from electronic and paper records. Newborn screening status was recorded, and patients were divided into ‘NIPE-positive’ (diagnosed through selective screening) and ‘NIPE-negative’ (not diagnosed through screening). Children with neuromuscular conditions or concomitant musculoskeletal disease were excluded. The tariff paid for each inpatient episode was identified, and the number of individual clinic attendances, surgical procedures and radiological examinations performed (USS, XR, CT, MRI) were recorded. Results. 41 patients with DDH were admitted for inpatient management. 44% (n = 18) were NIPE-positive, diagnosed mean age 6.7 weeks. 56% (n = 23) were NIPE-negative, diagnosed mean age 26 months. The total cost of inpatient care in the NIPE-positive group was £171,471 (£9,526.18 per-patient) compared to £306,615 (£13,331.10 per-patient) for NIPE-negative. In the NIPE-positive group, there were 99 clinic attendances, 47 inpatient admissions and 160 radiological examinations performed (36 USS, 107 XR, 17 CT). This compared to 148 clinic attendances, 59 inpatient admissions and 215 radiological examinations (187 XR, 26 CT, 2 MRI) in the NIPE-negative group. Conclusion. A greater proportion of inpatient admissions for DDH are among NIPE-negative children. They incur a higher cost of treatment per patient and necessitate more inpatient resources. This study adds to the ongoing conversation around the cost-effectiveness of selective screening for DDH in the UK. 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

Trauma and orthopaedics is the largest of the surgical specialties and yet attracts a disproportionately small fraction of available national and international funding for health research. With the burden of musculoskeletal disease increasing, high-quality research is required to improve the evidence base for orthopaedic practice. Using the current research landscape in the United Kingdom as an example, but also addressing the international perspective, we highlight the issues surrounding poor levels of research funding in trauma and orthopaedics and indicate avenues for improving the impact and success of surgical musculoskeletal research. Cite this article: Bone Joint J 2014; 96-B:1578–85

The growth in the popularity of tissue engineering principles in the treatment of musculoskeletal disorders has been complemented greatly with research investment into tissue specific scaffolds. Biological scaffolds produced by means of decellularising native tissues have the advantage of providing the natural complex hierarchical matrix and, in doing so, replicating the specific biomechanical and biological functions of the tissue in question. Decellularisation treatments are multi-faceted, vary considerably between different processes and may involve many lengthy treatment steps. Some of these bio-processes may cause undesirable structural changes to the extracellular matrix of tissues and, by association, their mechanical properties. Thus, it is of paramount importance to ensure that the properties of the scaffolds are not affected to the extent of reducing their integration, biomechanical performance and longevity. This talk consists of a body of work detailing investigations into bio-process optimisation, sterilisation strategies and the regenerative and functional capacity of decellularised xenogeneic and allogeneic tendon, ligament and bone scaffolds. In addition, on-going work concerning advanced pre-clinical assessment, stratification of these products to particular patient populations and the importance of the manufacturing value chain in their translation will be discussed

Osteoarthritis (OA) is the most common musculoskeletal disease in the EU and is characterized by cartilage degeneration, pain and restricted movement. Post-Traumatic OA (PTOA) is a specific disease subset that occurs subsequent to traumatic injury, such as ACL rupture and makes up 12% of the overall disease burden. Our current understanding PTOA is that initial injury affects multiple tissues, and many/all contribute to overall ‘joint failure.’ MRI scans show that subchondral bone marrow lesions (BMLs) are present in 80% of ACL rupture cases in the immediate aftermath of joint injury. Their presence indicates an acute consequence in subchondral bone. It has also been suggested that BMLs overlap with, or directly represent, bone microdamage. Microdamage is known to induce osteoclast-mediated remodelling in bone. Therefore, the inhibition of subchondral bone remodelling, particularly in the early phase post-injury, may be a candidate therapeutic approach for preventing PTOA. Finally, the contiguous link between subchondral bone and articular cartilage, can allow transport of small molecules across this boundary, this suggests that bone/cartilage crosstalk is likely to be a key factor in PTOA development after injury. This presentation will summarize recent advances in our understanding these phenomena in both animal and human studies