Approximately 30% of general practice consultations for musculoskeletal pain are related to tendon disorders, causing substantial personal suffering and enormous related healthcare costs. Treatments are often prone to long rehabilitation times, incomplete functional recovery, and secondary complications following surgical repair. Overall, due to their hypocellular and hypovascular nature, the regenerative capacity of tendons is very poor and intrinsically a disorganized scar tissue with inferior biomechanical properties forms after injury. Therefore, advanced therapeutic modalities need to be developed to enable functional tissue regeneration within a degenerative environment, moving beyond pure mechanical repair and overcoming the natural biological limits of tendon healing. Our recent studies have focused on developing biologically augmented treatment strategies for tendon injuries, aiming at restoring a physiological microenvironment and boosting endogenous tissue repair. Along these lines, we have demonstrated that the local application of mesenchymal stromal cell-derived small extracellular vesicles (sEVs) has the potential to improve rotator cuff tendon repair by modulating local inflammation and reduce fibrotic scarring. In another approach, we investigated if the local delivery of the tendon ECM protein SPARC, which we previously demonstrated to be essential for tendon maturation and tissue homeostasis, has the potential to enhance tendon healing. Finally, I will present results demonstrating the utility of nanoparticle-delivered, chemically modified mRNAs (cmRNA) to improve tendon repair

An increasing elderly population means joint replacement surgery numbers are projected to increase, with associated complications such as periprosthetic joint infections (PJI) also rising. PJI are particularly challenging due to antimicrobial resistant biofilm development on implant surfaces and surrounding tissues, with treatment typically involving invasive surgeries and systemic antibiotic delivery. Consequently, functionalisation of implant surfaces to prevent biofilm formation is a major research focus. This study characterises clinically relevant antimicrobials including gentamicin, clindamycin, daptomycin, vancomycin and caspofungin within a silica-based, biodegradable sol-gel coating for prosthetic devices. Antimicrobial activity of the coatings against clinically relevant microorganisms was assessed via disc diffusion assays, broth microdilution culture methods and the MBEC assay used to determine anti-biofilm activity. Human and bovine cells were cultured in presence of antimicrobial sol-gel to determine cytotoxicity using Alamar blue and antibiotic release was measured by LC-MS. Biodegradability in physiological conditions was assayed by FT-IR, ICP-MS and measuring mass change. Effect of degradation products on osteogenesis were studied by culturing mesenchymal stem cells in the presence of media in which sol-gel samples had been immersed. Antimicrobial-loaded coatings showed strong activity against a wide range of clinically relevant bacterial and fungal pathogens with no loss of activity from antibiotic alone. The sol-gel coating demonstrated controlled release of antimicrobials and initial sol-gel coatings showed no loss of viability on MSCs with gentamicin containing coatings. Current work is underway investigating cytotoxicity of sol-gel compositions against MG-63 cells and primary osteoblasts. This research forms part of an extended study into a promising antimicrobial delivery strategy to prevent PJI. The implant coating has potential to advance PJI infection prevention, reducing future burden upon healthcare costs and patient wellbeing

Background. Prosthetic implants used in primary total hip replacements have a range of bearing surface combinations (metal-on-polyethylene, ceramic-on-polyethylene, ceramic-on-ceramic, metal-on-metal); head sizes (small <36mm, large 36mm+); and fixation techniques (cemented, uncemented, hybrid, reverse hybrid), which influence prosthesis survival, patient quality of life, and healthcare costs. This study compared the lifetime cost-effectiveness of implants to determine the optimal choice for patients of different age and gender profiles. Methods. In an economic decision Markov model, the probability that patients required one or more revision surgeries was estimated from analyses of UK and Swedish hip joint registries, for males and females aged <55, 55–64, 65–74, 75–84, and 85+ years. Implant and healthcare costs were estimated from hospital procurement prices, national tariffs, and the literature. Quality-adjusted life years were calculated using utility estimates, taken from Patient-Reported Outcome Measures data for hip procedures in the UK. Results. Optimal choices varied between traditionally used cemented metal-on-polyethylene and cemented ceramic-on-polyethylene implants. Small head cemented ceramic-on-polyethylene implants were optimal for males and females aged under 65. The optimal choice for adults aged 65 and older was small head cemented metal-on-polyethylene implants. Conclusions. The older the patient, the higher the probability that small head cemented metal-on-polyethylene implants are optimal. Small head cemented ceramic-on-polyethelyne implants are optimal for adults aged under 65. Our findings can influence NICE guidance, clinical practice, and commissioning of services. Funding. NIHR Research for Patient Benefit programme PB-PG-0613-31032

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

Neck of femur fractures are a common presentation and certain patients can be managed with a total hip replacement. To receive a total hip replacement the pelvic X-rays should be templated as per AO guidelines and a common way this is performed is by including a calibration marker on the X-ray. The aim of this study is to assess and improve upon the use of the calibration marker. Details of patients admitted with a neck of femur fracture from January 1st 2018 until December 31st 2018 were gathered and used to review each initial X-ray and determine if a calibration marker was included. 376 patients were admitted with a neck of femur fracture over the one year period. 36% of patients did not have a calibration marker on their initial pelvic X-ray and 11% did not have a chest X ray. 215 patients had an intracapsular fracture and 39 went on to have a total hip replacement. 12 patients were lacking a calibration marker on their original X ray and required a repeat X ray. After a poster was placed in the radiographer booth acting as a visual aid, the use of a calibration marker improved from 62% to 70%. Calibration markers are useful tools which can aid the pre-operative planning for hip replacement surgeries shortening operative time, increase precision and reduce prosthetic loosening, lowers the risk of peri-prosthetic fractures, reduce leg length discrepancy and ensure the required implants are available. If a marker is not included on the initial X-rays, and a patient has a neck of femur fracture which requires a joint replacement, they may have to have additional X-rays performed as was the case for 12 patients in this study. This process leads to possible delays in surgery, additional radiation and increased healthcare costs

Cartilage diseases have a significant impact on the patient's quality of life and are a heavy burden for the healthcare system. Better understanding, early detection and proper follow-up could improve quality of life and reduce healthcare related costs. Therefore, the aim of this study was to evaluate if difference between osteoarthritic (OA) and non-osteoarthritic (non-OA) knees can be detected quantitatively on cartilage and subchondral bone levels with advanced but clinical available imaging techniques. Two OA (mean age = 88.3 years) and three non-OA (mean age = 51.0 years) human cadaveric knees were scanned two times. A high-resolution peripheral quantitative computed tomography (HR-pQCT) scan (XtremeCT, Scanco Medical AG, Switzerland) was performed to quantify the bone microstructure. A contrast-enhanced clinical CT scan (GE Revolution Evo, GE Medical Systems AG, Switzerland) was acquired with the contrast agent Visipaque 320 (60 ml) to measure cartilage. Subregions dividing the condyle in four parts were identified semi-automatically and the images were segmented using adaptive thresholding. Microstructural parameters of subchondral bone and cartilage thickness were quantified. The overall cartilage thickness was reduced by 0.27 mm between the OA and non-OA knees and the subchondral bone quality decreased accordingly (reduction of 33.52 % in BV/TV in the layer from 3 to 8 mm below the cartilage) for the femoral medial condyle. The largest differences were observed at the medial part of the femoral medial condyle both for cartilage and for bone parameters, corresponding to clinical observations. Subchondral bone microstructural parameters and cartilage thickness were quantified using in vivo available imaging and apparent differences between the OA and non-OA knees were detected. Those results may improve OA follow-up and diagnosis and could lead to a better understanding of OA. However, further in vivo studies are needed to validate these methods in clinical practice

Orthopaedic surgical site infections (SSI's) prolong total hospital stays by a median of 2 weeks per patient, approximately double re-hospitalization rates, and increase healthcare costs by more than 300%. Patients with orthopaedic SSI's have significant reductions in their health-related quality of life. We performed a systematic review and meta-analysis to compare differences in outcomes between use of sutures and non-absorbable staples for closure of orthopaedic surgical wounds in adults. The primary outcomes were rates of superficial and deep SSI. Secondary outcomes included wound dehiscence, length of hospital stay, patient satisfaction and pain during removal of closure material. Data sources including PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, . clinicaltrials.gov. , National Institute for Health and Research, UK clinical trials gateway were searched for randomised controlled trials (RCT's) meeting inclusion criteria. Sixteen RCT's published between 1987 and 2017 were included. Overall, wound infection outcomes (superficial and deep infections combined) showed no statistically significant difference between closure with staples compared with sutures with arelative risk of 1.17 (95% CI 0.59–2.30, p=0.66). A subgroup was performed specific to hip wound infection outcomes. Interestingly, a sensitivity analysis demonstrated sutures to be statistically favourable (p=0.04) in terms of hip wound infection outcomes. There was no statistically significant difference among secondary outcomes between sutures and staple groups. Overall it appears the choice of sutures or staples in closure of orthopaedic wounds has no effect on wound complications. However, caution is needed in applying the findings to different population groups due to heterogeneity across studies

Summary Statement. Pulmonary embolism (PE) after total knee arthroplasty can have a significant impact on patient outcomes and healthcare costs. Efforts to prevent or minimise PE over the last 10 years have not had a significant impact on its occurrence at the national level. Introduction. Pulmonary embolism (PE) is a rare but known potentially devastating complication of total knee arthroplasty (TKA). Significant healthcare resources and pharmaceutical research has been recently focused on preventing this complication but limited data exists regarding the early results of this great effort. The purpose of this study was to assess recent national trends in PE occurrence after TKA and evaluate patient outcomes related to this adverse event. Methods. International Classification of Disease - 9th Revision (ICD-9) procedure codes were used to search the National Hospital Discharge Survey (NHDS) for all patients admitted to US hospitals after primary TKA for each year between 2001 and 2010. ICD-9 diagnosis codes were then used to identify patients from this population who developed an acute PE during the same admission. Data regarding patient demographics, hospitalization length, discharge disposition, deep vein thrombosis, mortality, and hospital size/location were gathered from the NHDS. Trends were evaluated by linear regression with Pearson's correlation coefficient (r) and statistical comparisons were made using Student's t-test, z-test for proportions, and chi-square analysis with a significance level of 0.05. Results. 35,220 patients admitted for a primary TKA were identified. 159 (0.045%) of these patients developed an acute PE during the same admission. After adjusting for fluctuations in annual TKA performed, the development of PE after TKA demonstrated a weak negative correlation with time (r=0.17), insignificantly decreasing from an average rate of 0.049% between 2001–2005 to 0.041% between 2006–2010 (p=0.26). The size of the hospital was found to significantly impact the incidence of PE and primary TKA, with the lowest rate seen in hospitals under 100 beds (0.23%) and the highest rate seen in those with over 500 beds (0.65%, p=0.01). No significant differences in PE incidence were noted based on US region (p=0.38). The mean age of patients with PE was 67.7 years. This group included 54 men and 105 women. The non-PE group had a mean patient age that was insignificantly lower at 66.6 years (p=0.21) and included 12,450 men and 22,611 women. Gender was also not significantly different (p=0.68) between those with PE and those without PE. The number of medical co-morbidities was significantly higher in those with PE (mean 6.42 diagnoses) than those without PE (mean 4.89 diagnoses, p<0.01). Average hospitalization length also varied based on PE status, with significantly longer stays for those with PE (8.2 days, range 2–53) compared to those without PE (3.7 days, range 1–95, p<0.01). The rate of deep vein thrombosis was higher in the PE group (12.7%) versus the non-PE group (0.48%, p<0.01). Mortality was also significantly higher for the PE group (3.9%) compared to the non-PE group (0.09%, p<0.01). Discharge disposition did not significantly vary based on PE status, with 61.5% of PE and 64.0% of non-PE patients able to go directly home (p=0.59) after their inpatient stay. Discussion/Conclusion. This study demonstrates that PE can have a significant impact on patient outcomes and healthcare costs, with an associated 43-fold increase in mortality and a doubling of the inpatient admission duration. Additionally, although the risk of PE after primary TKA remains rare, it still persists. Efforts to prevent or minimise this complication over the last 10 years have not had a significant impact on its occurrence at the national level. This risk of PE appears to be greatest in patients with multiple medical co-morbidities and established DVTs. Interestingly, the PE rate also demonstrated variability based on hospital size. The reasons for this are not clear, but we suspect larger hospitals are more likely to be tertiary-care centers and thus care for more medically-complex patients

Background. Comminuted fractures involving the tibia are associated with a high level of complications including delayed healing and non-union, in conjunction with dramatically increased healthcare costs. Certain clinicians utilise a Pixel Value Ratio (PRV) of 1 to indicate such fracture healing. The subjectivity of this method has led to mixed outcomes including regenerate fracture. The poor prognosis of complex load bearing fractures is accentuated by the fact that no quantitative gold standard currently exists to which clinicians can reference regarding the definition of a healed fracture. The aim of the current study is to use patient specific finite element analysis of complex tibial fractures treated with Ilizarov frames to demonstrate callus maturation and to determine the optimum frame removal time. Methods. 3 patients (2 males, 1 female) were analysed following presentation with complex tibial fractures treated with Ilizarov frames. Patient specific computational analysis was performed according to radiographic data, incorporating maturing material properties to analyse the callus response to weight bearing over the healing timeframe. Computational results were compared to the PVR method to evaluate its efficacy in determining the optimum Ilizarov frame removal time. Results. All fractures were observed to clinically heal at a mean of 25.4 (±2.404) weeks. Following computational analysis however, the mean optimum Ilizarov frame removal time was seen to be 23.5 (±2.323) weeks. When compared with the PVR method, the suggested removal time presented a mean PVR of 1.025 (±0.017). Conclusion. Computational models of patient specific tibial fractures has shown promising correlations with the PVR method and has shown efficacy in predicting callus strength and subsequent optimum frame removal time. Level of Evidence. Level 4

Summary. Metal Injection Molding could provide cost saving of about 20–50% for implantable medical device manufacturing and hence healthcare public spending. Corrosion behaviour and biocompatibility of the new manufactured alloy were studied and showed similar behaviour compared to the traditional one. Introduction. The growing trend for total joint arthroplasties could raise healthcare costs in the near future. Metal Injection Molding (MIM) is a near net shape manufacturing technology and allows the production of finite prosthesis components saving the machining step, and so resources, up to 20–50%. In order to apply such process to the production of actual devices, the bulk material have to show biocompatibility and corrosion behaviour similar to the traditional one. (ASTM F2083, ISO 21536) The aim of this work was to compare cast and forged CoCrMo alloy with the MIM one from the electrochemical point of view and cytocompatibility. Material and Methods. Metallographic observations by optical microscopy and SEM were taken to better understand the electrochemical behaviour. This evaluation was performed through potentiodynamic tests on MIM and forged (FOR) samples with polished and sandblasted surfaces (as the actual devices), in ASTM G5 cell with saline solution simulating the body environment, graphite counter electrodes and Ag/AgCl 0.15M NaCl reference electrode. Linear polarization, open circuit potential measurements and potentiostatic tests at +335 mV vs SCE were also performed during 10 days to have direct information on the corrosion resistance and ion release. Cell viability were also assessed through MTT test on polished MIM and cast (CAS) elutes, after 2 and 7 days contact periods, following ISO 10993 directions. Static ion release in H. 2. O at 2, 4 and 8 weeks were also performed. Results. MIM showed coarser grains, free of boundary carbide but with lots of circular porosities and stacking faults, in comparison with CAS structure, which presented many carbides and typical dendritic grain. Electrochemical tests exhibited analogue behaviour for the MIM and FOR CoCrMo alloys. The slightly lower passive current density and transpassive potential values obtained could be ascribed to a passive oxide layer on the MIM sample less protective than FOR CoCrMo one, as inferable from the OCP measurements, but these facts had no visible influence on polarization resistance and ion release. Such good corrosion behaviour was reflected also in static ion release results and MTT viability results, which were comparable, not only to CAS samples but also to the control medium. Conclusions. From such preliminary results MIM technology showed to have good possibility for the production of implantable medical devices with CoCrMo alloy. Corrosion resistance and biocompatibility seemed not to be affected by the different manufacturing technique. Further studies will be needed to asses also the equivalence of mechanical properties. From the metallographic observations the absence of second phases and the homogeneous microstructure suggests a better fatigue performance for this kind of alloy, even if some concerns arise from the widespread porosity observed

Objectives

Surgeons face a substantial risk of infection because of the occupational exposure to blood-borne pathogens (BBPs) from patients undergoing high-risk orthopaedic procedures. This study aimed to determine the seroprevalence of four BBPs among patients undergoing joint arthroplasty in Shanghai, China. In addition, we evaluated the significance of pre-operative screening by calculating a cost-to-benefit ratio.

Objectives

The present study describes a novel technique for revitalising allogenic intrasynovial tendons by combining cell-based therapy and mechanical stimulation in an ex vivo canine model.