Abstract. Introduction. Several studies have shown that patients over 65 years have a higher mortality with covid. Combine with inherently increased morbidity and mortality in neck of femur (NoFF) fractures, it is logical to think that this subset would be most at risk. Aims. Investigate whether there is actual increase in direct mortality from Covid infection in NoFF patients, also investigate other contributing factors to mortality with covid positivity and compare the findings with current available literature. Methods. 1-year cross sectional, retrospective study from 1st March 2020 at two DGHs, one in Wales and one in England. Surgically treated NoFF patients with isolated intra/extracapsular fracture included. Mortality analysis done by creating a matched comparison group for each risk factor and combinations known to confer highest mortality. Chi square test for independence used to compare COVID status with 1 year mortality. Results. 610 patients, 62 patients had COVID-19RTPCR+ive test during hospital stay/in the community. 21(34%) deaths in COVID positive and 95 (17.33%) deaths in COVID negative patients. There was no mortality in ASA 1 or 2 patients. Analysis of asa matching with 10-year age ranges from 65years revealed a nearly double mortality rate in covid+ group as opposed to covid negative for both ASA 3 and 4 groups. Parameters such as preinjury mobility, residential status, AMTS score, time to surgery, did not seem to play a significant role in mortality. Conclusion. First of its kind study with a large subset of patients and unique parameters to identify causes leading to mortality in the vulnerable population of NoFF. Higher morality in Covid positive NoFF patients, but increase may not be as significant as identified by most current studies in the literature and still within the confines of NHFD stats(2019). 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

COVID-19 was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The initial response to the pandemic included the cessation of routine services including elective orthopaedic surgery. There was apprehension among both surgeons and patients about restarting elective surgical services. The high mortality rate in perioperative patients who contract COVID-19 was of particular concern. The aim of this study was to identify the perioperative viral transmission rate in orthopaedic patients at our institution following the restart of elective surgery between August 2020 and November 2020 after the first wave of Covid in the UK. All patients who had their elective Orthopaedic surgeries at our institution from 1st August 2020 to 30th November 2020 were checked whether they were Covid positive or experienced COVID symptoms within 2 weeks after the operation. All patients were advised a 14-day period of comprehensive social distancing, 3 days of self-isolation and had a negative COVID-19 test within 72 hours of surgery and underwent surgery at a COVID free site. The patients were contacted and the hospital database was searched to identify those patients who were Covid positive or had Covid symptoms after the surgery. Baseline patient characteristics were recorded including age, gender, procedure, the subspeciality and admission type. Patients who underwent emergency procedures and trauma operations were excluded. Out of the 499 patients, 315 were contacted over telephone and hospital database was searched for the rest of the patients. We found that none of the patients were positive for COVID or had symptoms of COVID within two weeks of surgery. 5 patients were COVID positive with symptoms few months after the procedure and all of them recovered. There were 144 inpatient admissions and 353 day cases. The development of a COVID-free pathway for elective orthopaedic patients results in very low viral transmission rates. Findings of our study confirms that COVID-free elective pathway is an efficient process, and this could be implemented in future elective Orthopaedic surgeries during COVID times. Elective surgery can be safely resumed using dedicated pathways and procedures -Surgeons, hospital staff and patients should remain vigilant

Object. The aim of this study was to investigate the impact of the COVID-19 pandemic on the management and outcome of patients with neck of femur fractures. Methods. Data was collected for 96 patients with neck of femur fractures who presented to the emergency department between March 1, 2020 and May 15, 2020. This data set included information about their COVID-19 status. Parameters including inpatient complications, hospital quality measures, mortality rates, and training opportunities were compared between the COVID-19 positive and COVID-19 negative groups. Furthermore, our current cohort of patients were compared against a historical control group of 95 patients who presented with neck of femur fractures before the COVID-19 pandemic. Results. Seven (7.3%) patients were confirmed COVID positive by RT-PCR testing. The COVID positive cohort, when compared to the COVID negative cohort, had higher rates of postoperative complications (71.4% vs 25.9%), increased length of stay (30.3 days vs 12 days) and quicker time to surgery (0.7 days vs 1.3 days). The 2020 cohort compared to the 2019 cohort, had an increased 30-day mortality rate (13.5% vs 4.2%), increased number of delayed cases (25% vs 11.8%) as well as reduced training opportunities for Orthopaedic trainees to perform the surgery (51.6% vs 22.8%). Conclusions. COVID-19 has had a profound impact on the care and outcome of neck of femur fracture patients during the pandemic with an increase in 30-day mortality rate. There were profound adverse effects on patient management pathways and outcomes while also affecting training opportunities

Abstract. BACKGROUND. Hemi-arthroplasty (HA) as a treatment for fractured neck of femur has slightly increased since 2019 and remarkably after the COVID pandemic. The main drawback of the treatment is ongoing cartilage deterioration that may require revision to THR. OBJECTIVE. This study assessed cartilage surface damage in hip HA by reproducing anatomical motion and loading conditions in a hip simulator. METHODS. Experimental design. HA tests were conducted using porcine acetabula and CoCr femoral heads. Five groups (n=4) were included: a control group comprising natural tissue and four HA groups where the acetabula were paired with metal heads to allow radial clearance (RC) classed as small (RC<0.6mm), large (2mm<RC<4mm), extra-large (4mm<RC), and oversized (RC<−0.6mm). Tests were carried out in an anatomical hip simulator that reproduced a simplified twin peak gait cycle, adapted for porcine hip joints, from the ISO 14242 standard for wear of THR prostheses (peak load of 900N). The test length was 6 hours, with photogrammetry taken at 1-hour intervals. Ringers solution was used as a lubricant. RESULTS. No changes were observed in the control group. However, cartilage surface changes were observed in all hemi-arthroplasty groups. Discolouration on the cartilage surface was noticeable at the posterior-superior part of the acetabulum after 1-hour (extra-large and oversized groups). Damage severity and location were characteristic of each clearance group. Of all the groups, the oversized group showed more significant damage. No labrum separation was seen after the simulation. CONCLUSIONS. These results are relevant to understand the effect of femoral head clearance on cartilage damage risk after HA. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

The e-scooter trial was part of a wider initiative from the Department for Transport in response to COVID pandemic. New emergency legislation was introduced in 2020 to make e-scooters legal in the UK for the first time. This scheme was launched in our county from September 2020. The aim of this case series was to identify the types of Orthopedic injuries resultant from electric scooter transport that presented to our District General Hospital over a 16-month period between September 2020 and December 2021. This study involved retrospective collection of data from electronic hospital records. Data on demographics, laterality, date of injury, type of injury, treatment, HDU/ITU admissions, mortality, and operating time were collected to characterize the types of e-scooter-related injuries and to investigate the frequency of such injuries over the duration of our search. A total of 79 orthopedic patients identified with electric scooter injuries between September 2020 and December 2021. 78.5% were males and the mean age was 30.1 years. Summer months accounted for most of the injuries. 17 patients required inpatient care. 23 patients required surgical intervention and a total of 29 surgeries were performed in our hospital. This accounted for a total surgical time of 2088 minutes. One patient admitted with shaft of femur fracture developed pulmonary embolism after the definitive operation and died in HDU. Electric scooters provide a space efficient, affordable, environmentally friendly mode of transportation which reduce the urban congestion and parking issues. This study demonstrates an increasing frequency of significant orthopedic injury associated with e-scooter use treated at our centre over the course of 16 months. This small series underlines an important problem given that this increase has occurred after the start of the electric scooter trial. Legalization might result in further increase in the incidence of injury

Virtual physiotherapy has been provided to hundreds of patients at the Holland Centre during the COVID pandemic. As we plan for virtual care to be one part of our care delivery we want to evaluate it and ensure the care delivery is safe and effective. The objectives of this project was two-fold: 1) to examine the outcome of virtual physiotherapy and/ or a hybrid of virtual and in-person care in patients who received post-operative treatment following total knee replacement at the Holland Centre, 2) to explore the challenges of virtual care participation in the joint replacement population. Patients who received either virtual care or a combination of in-person and virtual care (hybrid model) based on the patients’ needs were included. Patient-related outcomes were the Patient Specific Functional Scale (PSFS) and pain scale. Flexion and extension range of motion were measured before and after treatment. A modified Primary Care Patient Experience Virtual Care Survey was used to examine barriers for virtual care. Sixty patients, mean age 68(8), ranging between 45-83 years, 34(57%) females, who received either virtual care or a combination of in-person and virtual care based on the patients’ needs were included. Patients showed improvement in the PSFS and pain scores (p<0.0001). Flexion (p<0.0001) and extension (p=0.02) improved at a statistically significant level. A separate sample (N=54) (age range 50-85 years) completed the patient experience survey. A well-designed post-operative virtual physiotherapy program, initially implemented to maintain continuity of care during the pandemic, continues to be an important part of our model of care as we normalize our activities. Clear understanding of barriers to virtual care and mitigation strategies will help us create virtual care standards, meet our patient needs, optimize our care delivery and potentially increase the use of virtual rehab in the future

Introduction. PIEZO mechanoreceptors are increasingly recognized to play critical roles in fundamental physiological processes like proprioception, touch, or tendon biomechanics. However, their gating mechanisms and downstream signaling are still not completely understood, mainly due to the lack of effective tools to probe these processes. Here, we developed new tailor-made nanoswitches enabling wireless targeted actuation on PIEZO1 by combining molecular imprinting concepts with magnetic systems. Method. Two epitopes from functionally relevant domains of PIEZO1 were rationally selected in silico and used as templates for synthesizing molecularly imprinted nanoparticles (MINPs). Highly-responsive superparamagnetic zinc-doped iron oxide nanoparticles were incorporated into MINPs to grant them magnetic responsiveness. Endothelial cells (ECs) and adipose tissue-derived stem cells (ASCs) incubated with each type of MINP were cultured under or without the application of cyclical magnetomechanical stimulation. Downstream effects of PIEZO1 actuation on cell mechanotransduction signaling and stem cell fate were screened by analyzing gene expression profiles. Result. Nanoswitches showed sub-nanomolar affinity for their respective epitope, binding PIEZO1-expressing ECs similarly to antibodies. Expression of genes downstream of PIEZO1 activity significantly changed after magnetomechanical stimulation, demonstrating that nanoswitches can transduce this stimulus directly to PIEZO1 mechanoreceptors. Moreover, this wireless actuation system proved effective for modulating the expression of genes related to musculoskeletal differentiation pathways in ASCs, with RNA-sequencing showing pronounced shifts in extracellular matrix organization, signal transduction, or collagen biosynthesis and modification. Importantly, targeting each epitope led to different signaling effects, implying distinct roles for each domain in the sophisticated function of these channels. Conclusion. This innovative wireless actuation technology provides a promising approach for dissecting PIEZO-mediated mechanobiology and suggests potential therapeutic applications targeting PIEZO1 in regenerative medicine for mechanosensitive tissues like tendon. Acknowledgements. EU's Horizon 2020 ERC under grant No. 772817 and Horizon Europe under grant No. 101069302; FCT/MCTES for PD/BD/143039/2018, COVID/BD/153025/2022, 10.54499/2020.03410.CEECIND/CP1600/CT0013, 10.54499/2022.05526.PTDC, 10.54499/UIDB/50026/2020, 10.54499/UIDP/50026/2020, and 10.54499/LA/P/0050/2020

Tendon diseases are prevalent health concerns for which current therapies present limited success, in part due to the intrinsically low regenerative ability of tendons. Therefore, tissue engineering presents a potential to improve this outcome. Here, we hypothesize that a concurrent control over both biophysical and biochemical stimuli will boost the tenogenic commitment of stem cells, thus promoting regeneration. To achieve this, we combine molecularly imprinted nanoparticles (MINPs), which act as artificial amplifiers for endogenous growth factor (GF) activity, with bioinspired anisotropic hydrogels. 2. to manufacture 3D tenogenic constructs. MINPs were solid phase-imprinted using a TGF-β3 epitope as template and their affinity for the target was assessed by SPR and dot blot. Magnetically-responsive microfibers were produced by cryosectioning electrospun meshes containing iron oxide nanoparticles. The constructs were prepared by encapsulating adipose tissue-derived stem cells (ASCs), microfibers, and MINPs within gelatin hydrogels, while aligning the microfibers with an external magnetostatic field during gelation. This allows an effective modulation of hydrogel fibrillar topography, mimicking the native tissue's anisotropic architecture. Cell responses were analyzed by multiplex immunoassay, quantitative polymerase chain reaction, and immunocytochemistry. MINPs showed an affinity for the template comparable to monoclonal antibodies. Encapsulated ASCs acquired an elongated shape and predominant orientation along the alignment direction. Cellular studies revealed that combining MINPs with aligned microfibers increased TGF-β signaling via non-canonical Akt/ERK pathways and upregulated tendon-associated gene expression, contrasting with randomly oriented gels. Immunostaining of tendon-related proteins presented analogous outcomes, corroborating our hypothesis. Our results thus demonstrate that microstructural cues and biological signals synergistically direct stem cell fate commitment, suggesting that this strategy holds potential for improving tendon healing and might be adaptable for other biological tissues. The proposed concept highlights the GF-sequestering ability of MINPs which allows a cost-effective alternative to recombinant GF supplementation, potentially decreasing the translational costs of tissue engineering strategies. Acknowledgements: The authors acknowledge the funding from the European Union's Horizon 2020 under grant No. 772817; from FCT/MCTES for scholarships PD/BD/143039/2018 & COVID/BD/153025/2022 (S.P.B.T.), and PD/BD/129403/2017 (S.M.B.), co-financed by POCH and NORTE 2020, under the Portugal 2020 partnership agreement through the European Social Fund, for contract 2020.03410.CEECIND (R.M.A.D.) and project 2022.05526.PTDC; and from Xunta de Galicia for grant ED481B2019/025 (A.P.)

Fracture nonunion is a severe clinical problem for the patient, as well as for the clinician. About 5-20% of fractures does not heal properly after more than six months, with a 19% nonunion rate for tibia, 12% for femur and 13% for humerus, leading to patient morbidity, prolonged hospitalization, and high costs. The standard treatment with iliac crest-derived autologous bone filling the nonunion site may cause pain or hematoma to the patient, as well as major complications such as infection. The application of mesenchymal autologous cells (MSC) to improve bone formation calls for randomized, open, two-arm clinical studies to verify safety and efficacy. The ORTHOUNION * project (ORTHOpedic randomized clinical trial with expanded bone marrow MSC and bioceramics versus autograft in long bone nonUNIONs) is a multicentric, open, randomized, comparative phase II clinical trial, approved in the framework of the H2020 funding programme, under the coordination of Enrique Gòmez Barrena of the Hospital La Paz (Madrid, Spain). Starting from January 2017, patients with nonunion of femur, tibia or humerus have been actively enrolled in Spain, France, Germany, and Italy. The study protocol encompasses two experimental arms, i.e., autologous bone marrow-derived mesenchymal cells after expansion (‘high dose’ or ‘low dose’ MSC) combined to ceramic granules (MBCP™, Biomatlante), and iliac crest-derived autologous trabecular bone (ICAG) as active comparator arm, with a 2-year follow-up after surgery. Despite the COVID 19 pandemic with several lockdown periods in the four countries, the trial was continued, leading to 42 patients treated out of 51 included, with 11 receiving the bone graft (G1 arm), 15 the ‘high dose’ MSC (200x10. 6. , G2a arm) and 16 the ‘low dose’ MSC (100x10. 6. , G2b arm). The Rizzoli Orthopaedic Institute has functioned as coordinator of the Italian clinical centres (Bologna, Milano, Brescia) and the Biomedical Science and Technologies and Nanobiotechnology Lab of the RIT Dept. has enrolled six patients with the collaboration of the Rizzoli’ 3rd Orthopaedic and Traumatological Clinic prevalently Oncologic. Moreover, the IOR Lab has collected and analysed the blood samples from all the patients treated to monitor the changes of the bone turnover markers following the surgical treatment with G1, G2a or G2b protocols. The clinical and biochemical results of the study, still under evaluation, are presented. * ORTHOUNION Horizon 2020 GA 733288

Abstract. Introduction. The long-term biological success of cementless orthopaedic prostheses is highly dependent on osteointegration. Pre-clinical testing of new cementless implant technology however, requires live animal testing, which has anatomical, loading, ethical and cost challenges. This proof-of-concept study aimed to develop an in vitro model to examine implant osteointegration under known loading/micromotion conditions. Methods. Fresh cancellous bone cylinders (n=8) were harvested from porcine femur and implanted with additive manufactured porous titanium implants (Ø4 × 15 mm). To simulate physiological conditions, n=3 bone cylinders were tested in a bioreactor system with a cyclic 30 µm displacement at 1Hz for 300 cycles every day for 15 days in a total of 21 days culture. The chamber was also perfused with culture medium using a peristaltic pump. Control bone cylinders were cultured under static conditions (n=5). Samples were calcein stained at day 7. Post-testing, bone cylinders were formalin fixed and bony ingrowth was measured via microscopy. Results. Viability of the freshly harvested ex vivo bone cylinders was maintained for up to 28 days. Two samples remain unanalysed due to COVID lockdown, one in each group. Similar to osteointegration seen in live animal models, evidence of bony ingrowth was seen more markedly at the bone-implant interface under dynamic conditions. This was evident by a greater intensity of calcein staining, confirming the deposition of new bone, at the bone-implant interface. In comparison, under static conditions, calcein staining was observed randomly all over the cylinder. Conclusion. This proof-of-concept study demonstrates that implant bony adaptation and ingrowth can be measured in vitro under known cyclic micromotion/loading conditions. This comparatively low cost, low ethical impact, controlled loading laboratory method has potential to accelerate the rate of implant development whilst conforming with the principles of NC3Rs. 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