Abstract

Abstract

C. Difficile infections in elderly patients with hip fractures is associated with high morbidity and mortality. Antibiotic regimens with penicillin and its derivatives is a leading cause. Antibiotic prophylactic preferences vary across different hospitals within NHS. We compared two antibiotic prophylactic regimens - Cefuroxime only prophylaxis and Teicoplanin with Gentamicin prophylaxis in fracture neck of femur surgery, and evaluated the incidence of C. Difficile diarrhea and Surgical Site Infection (SSI).

To assess the Surgical Site Infection and C. Difficile infection rate associated with different regimens of antibiotics prophylaxis in fracture neck of femur surgery.

Data was analyzed retrospectively. Neck of femur fracture patients treated surgically from 2009 in our unit were included. Age, gender, co morbidities, type of fracture, operation, ASA grade was collected. 1242 patients received Cefuroxime only prophylaxis between January 2009 and December 2012 (Group 1) and 486 patients received Teicoplanin with Gentamicin between October 2015 and March 2017 (Group 2). There were 353 males and 889 female patients in Group 1 and 138 males and 348 female patients in Group 2. The co morbidities in both groups were comparable. Incidence of C. Difficile diarrhea and Surgical Site Infection (SSI) was noted. Statistical analysis with chi square test was performed to determine the ‘p’ value.

C. Diff diarrhea rate in Group 2 was 0.41 % as compared to 1.29 % in Group 1. The Surgical Site Infection (SSI) rate in Group 2 was 0.41 % as compared to 3.06 % in Group 1. The comparative results were statistically significant (p = 0.0009).

Prophylactic antibiotic regimen of Teicoplanin with Gentamicin showed significant reduction in C. Difficile diarrhea & Surgical Site Infection in fracture neck of femur patients undergoing surgery.

Cannulated hip screws are frequently used in the management of hip fractures. There have been concerns over the failure rate of the technique and the outcomes of those that subsequently require conversion to total hip replacement (THR).

This study utilised a database of over 600 cannulated hip screw (CHS) fixations performed over a 14-year period and followed up for a minimum of one year (1-14). We identified 57 cases where a conversion to THR took place (40 females, 17 males, mean age: 71.2 years). Patient demographics, original mechanism of injury, fracture classification, reason for fixation failure, time until arthroplasty, implant type and post-arthroplasty complications were recorded. Clinical outcomes were measured using the Oxford Hip Score.

The failure rate of cannulated screw treatment was 9.4% and the mean time from initial fixation to arthroplasty was 15.4 (16.5) months. Thirty six fractures were initially undisplaced and 21 were displaced. As one might expect the displaced cases tended to be younger but this didn't reach statistical significance [66.5(14.3) vs 72.7(13.1), p=0.1]. The commonest causes of failure were non-union (25 cases, 44%) and avascular necrosis (17 cases, 30%). Complications after THR consisted of one leg length discrepancy and one peri-prosthetic fracture. The mean Oxford score pre-arthroplasty was 12.2 (8.4), improving to 38.4 (11.1) at one-year. Although the pre op Oxford scores tended to be lower in patients with undisplaced fractures and higher ASA scores, the improvement was the same whatever the pre-op situation. The one-year Oxford score and the improvement in score are comparable to those seen in the literature for THR in general.

In conclusion, CHS has a high success rate and where salvage arthroplasty is required it can provide good clinical outcomes with low complication rates.

Abstract

Total hip replacement (THR) is indicated for patients with osteoarthritis where conservative treatment has failed. Metal alloys used in THR implants such as cobalt-chromium (CoCr) have been known to cause pro-inflammatory reactions in patients, therefore leading to the need for costly revision surgery. This study therefore aimed to investigate the role of TLR4 in the activation of a human osteoblast model in response to CoCr particles in vitro.

Human osteoblasts (MG-63 cell line) were seeded at a density of 100,000 cells and treated with 0.5, 5, 50mm3 CoCr particles per cell for 24-hours. Trypan blue and the XTT Cell Proliferation Kit II were then used in conjunction with the cells to assess CoCr-induced cytotoxicity. Cells were pre-treated with a commercially available TLR4-specific small molecule inhibitor (CLI-095) for 6 hours. Untreated cells were used as a negative control and lipopolysaccharide (LPS) was used as a positive control. Following treatment the cell supernatant was collected and used for enzyme-linked immunosorbant assay (ELISA) to measure the secretion of interleukin-8 (IL-8), CXCL10, and interleukin-6 (IL-6).

Trypan blue and XTT analysis showed that there was no significant changes to cell viability or proliferation at any dose used of CoCr after 24 hours. There was a significant increase in protein secretion of IL-8 (p<0.001), CXCL10 (p<0.001), and IL-6 (p<0.001) in the cells which received the highest dosage of CoCr. This pro-inflammatory secretory response was ameliorated by TLR4 blockade (p<0.001).

CoCr particles are not cytotoxic to osteoblasts but they do induce pro-inflammatory changes as characterised by increased secretion of chemokines IL-8, CXCL10, and IL-6. These responses occur via a TLR4-mediated pathway and upon inhibition they can be effectively ameliorated. This is particularly important as TLR4 could be a potential target for pharmacological intervention used in patients experiencing immunological reactions to metal implant debris.

Plantar fasciitis (PF) is one of the widespread conditions causing hindfoot pain. The most common presenting symptoms are functional limitation and pain (first step and activity) on plantar surface of the foot. The non-operative treatments provide complete resolution of pain in 90% of patients, but functional limitation still remains as a risk factor for recurrency of PF. Although the number of non-operative treatment options showing efficacy on pain and functional limitation are excessive, the evidences are limited for functional limitation. Additionally, Mulligan mobilization with movement (MMWM) in Chronic Plantar Fasciitis has been poorly studied in the literature. According to these findings, the study was aimed to determine effectiveness of Mulligan mobilization with movement on Chronic Plantar Fasciitis.

A total of 25 patients (40 feet) with chronic PF were included in the study. The patients were randomly divided into Mulligan concept rehabilitation group (PF-M, n=20 feet) and Home Rehabilitation group (PF-H, n=20 feet). (MMWM), Foot and ankle exercises program were applied to PF-M, twice a week totally 8 week (16 sessions) and foot- ankle exercises as a home program were given for PF-H, 8 weeks. The range of motion (ROM) for dorsiflexion and plantar flexion was measured by using a manual goniometer. Pain, disability and activity restriction were assessed by Foot Function Index (FFI) . The first step morning pain was evaluated by Visual Analogue Scale (VAS) and Kinesiophobia was also reported by using Tampa Scale (TSK). Patients were evaluated at baseline and 8 weeks.

FFI, VAS, TSK, ROM values improved in all groups (intragroup variability) at 8th week (P < .05). The other result indicated that ROM values for DF and PF and TSK scores in PF-M had more significant improvement than PF-H (p<.05).

To the best of our knowledge this is the first randomised controlled trial for investigating Mulligan Concept efficiancy on chronic PF. Both Mulligan mobilization with movement (MMWM) and exercise protocols are effective for chronic PF. Furthermore, The Mulligan concept seems more effective treatment option in reducing kinesiophobia and improving functional capacity.

Background

Low back pain (LBP) is a major problem across the globe and is the leading cause worldwide of years lost to disability. Self-management is considered an important component the treatment of people with non-specific LBP. However, it seems that the self-management support for people with non-specific LBP provided by physiotherapists can be improved. Moreover, the way exercise therapists (ET) address self-management in practice is unknown.

Femoral stem design affects periprosthetic bone mineral density (BMD), which may impact long term survival of cementless implants in total hip arthroplasty (THA). The aim of this study was to examine proximal femoral BMD in three morphologically different uncemented femoral stems designs to investigate whether one particular design resulted in improved preservation of BMDMethods: 119 patients were randomised to receive either a proximally coated dual taper wedge stem, a proximally coated anatomic stem or a fully coated collarless triple tapered stem. All surgeries were performed via the posterior approach with mobilization on the day of surgery. Dual energy x-ray absorptiometry scans (Lunar iDXA, GE Healthcare, Madison, WI) assessed BMD across the seven Gruen zones pre-operatively, and post-operatively at 6-weeks, 1-year, and 2-years and compared to the unoperated contralateral femur as a control. Patient reported outcome measures of pain, function and health were also included at these corresponding follow-ups.

BMD increased in zones one (2.5%), two (17.1%), three (13.0%), five (10%) and six (17.9%) for all stems. Greater preservation of BMD was measured on the lateral cortex (zone 2) for both the dual taper wedge and anatomic stems (p = 0.019). The dual taper wedge stem also demonstrated preservation of BMD in the medial calcar (zone 7) whilst the anatomic and triple taper stem declined in this region, however this was not statistically significant (p = 0.059). BMD decreased on average by 2.1% inthe mid-diaphysis region, distal to the stem tip (zone 4) for all implants. All stems performed equivalently at final follow-up in all patient reported outcome measures.

This study demonstrated maintenance of femoral BMD in three different cementless femoral stem designs, with all achieving excellent improvements in patient reported outcomes. There was no significant stress shielding observed, however longer follow-up is required to elucidate the impact of this finding on implant survivorship.

Aim

To determine mortality and outcomes of patients diagnosed with fracture-related infections (FRIs).

The purpose of this study was to develop a quality appraisal tool for the assessment of laboratory basic science biomechanical studies.

Materials andScore development comprised of the following phases: item identification/development, item reduction, content/face/criterion validity, weighting, test-retest reliability and internal consistency. For item identification/development, the panel was asked to independently list criteria and factors they considered important for cadaver study and generate items that should be used to appraise cadaver study quality. For content validity, the content validity ratio (CVR) was calculated. The minimum accepted content validity index (CVI) was set to 0.85. For weighting, equal weight for each item was 6.7% [15 items]. Based on these figures the panel was asked to either upscale or downscale the weight for each item ensuring that the final sum for all items was 100%. Face validity was assessed by each panel member using a Likert scale from 1–7. Strong face validity was defined as a mean score of >5. Test-retest reliability was assessed using 10 randomly selected studies. Criterion validity was assessed using the QUACS scale as standard. Internal consistency was assessed using Cronbach's alpha.

Five items reached a CVI of 1 and 10 items a CVI of 0.875. For weighting five items reached a final weight of 10% and ten items 5%. The mean score for face validity was 5.6. Test-retest reliability ranged from 0.78–1.00 with 9 items reaching a perfect score. Criterion validity was 0.76 and considered to be strong. Cronbach's alpha was calculated to be 0.71 indicating acceptable internal consistency.

The new proposed quality score for basic science studies consists of 15 items and has been shown to be reliable, valid and of acceptable internal consistency. It is suggested that this score should be utilised when assessing basic science studies.

This study aimed to examine the changing trends in the reasons for total hip replacement (THR) revision surgery, in one country over a twenty-one year period, in order to assess whether changes in arthroplasty practices have impacted revision patterns and whether an awareness of these changes can be used to guide clinical practice and reduce future revision rates.

The reason for revision THR performed between January 1999 and December 2019 was extracted from the New Zealand Joint Registry (NZJR). The results were then grouped into seven 3-year periods to allow for clearer visualization of trends. The reasons were compared across the seven time periods and trends in prosthesis use, patient age, gender, BMI and ASA grade were also reviewed. We compared the reasons for early revision, within one year, with the overall revision rates.

There were 20,740 revision THR registered of which 7665 were revisions of hips with the index procedure registered during the 21 year period. There has been a statistically significant increase in both femoral fracture (4.1 – 14.9%, p<0.001) and pain (8.1 – 14.9%, p<0.001) as a reason for hip revision. While dislocation has significantly decreased from 57.6% to 17.1% (p<0.001). Deep infection decreased over the first 15 years but has subsequently seen further increases over the last 6 years. Conversely both femoral and acetabular loosening increased over the first 12 years but have subsequently decreased over the last 9 years. The rate of early revisions rose from 0.86% to 1.30% of all revision procedures, with a significant rise in revision for deep infection (13-33% of all causes, p<0.001) and femoral fracture (4-18%, p<0.001), whereas revision for dislocation decreased (59-30%, p<0.001). Adjusting for age and gender femoral fracture and deep infection rates remained significant for both (p<0.05). Adjusting for age, gender and ASA was only significant for infection.

The most troubling finding was the increased rate of deep infection in revision THR, with no obvious linked pattern, whereas, the reduction in revision for dislocation, aseptic femoral and acetabular loosening can be linked to the changing patterns of the use of larger femoral heads and improved bearing surfaces.

Abstract

Fractures of the ankle are common, and they mostly affect young adults. Wound complications are not uncommon following the fixation of these fractures. This study evaluated the impact of HIV on wound healing after plate osteosynthesis in patients with closed ankle fractures.

This is an observational retrospective study of patients operated on at a tertiary level hospital. We reviewed hospital records for patients above 18 years of age who presented with wound breakdown following ankle open reduction and internal fixation. The patients’ hospital records were retrieved to identify all the patients treated for closed ankle fractures and those who developed wound breakdown. Patients with Pilon fractures were excluded. The National Health Laboratory System (NHLS) database was accessed to retrieve the CD4 count, viral load, haematology study results, and biochemistry results of these patients at the time of surgery and subsequent follow-up. The x-rays were retrieved from the electronic picture archiving system (PACS) and were assessed for fracture union at a minimum of 3 months follow-up.

We reviewed the medical records of 172 patients with closed ankle fractures treated from 2018 to 2022. Thirty-one (18.0%) developed wound breakdown after surgery, and they were all tested for HIV. Most of the patients were male (58.0%), and the average age of the cohort was 43.7 years (range: 21 years to 84 years). Ten of these patients (32.2%) were confirmed HIV positive, with CD4 counts ranging from 155 to 781. Viral load levels were lower than detectable in 40% of these patients. All patients progressed to fracture union at a minimum of 3 months follow-up.

We observed no difference between HIV-positive and HIV-negative patients in terms of wound breakdown and bone healing post-plate osteosynthesis for closed ankle fractures.

To investigate whether anterior pelvic plane-pelvic tilt (APP-PT) is associated with distinct hip pathomorphologies, we asked: (1) Is there a difference in APP-PT between symptomatic young patients eligible for joint preservation surgery and an asymptomatic control group? (2) Does APP-PT vary between distinct acetabular and femoral pathomorphologies? (3) Does APP-PT differ in symptomatic hips based on demographic factors?

IRB-approved, single-center, retrospective, case-control, comparative study in 388 symptomatic hips (357) patients (mean age 26 ± 2 years [range 23 to 29], 50% females) that presented to our tertiary center for joint preservation over a five year-period. Patients were allocated to 12 different morphologic subgroups. The overall study group was compared to a control group of 20 asymptomatic hips (20 patients). APP-PT was assessed in all patients based on AP pelvis X-rays using the validated HipRecon software. Values between overall and control group were compared using an independent samples t-test. Multiple regression analysis was performed to examine the influences of diagnoses and demographic factors on APP-PT. Minimal clinically important difference (MCID) of APP-PT was defined as >1 standard deviation.

No significant differences in APP-PT between the control group and overall group (1.1 ± 3.0° [−4.9 to 5.9] vs 1.8 ± 3.4° [−6.9 to 13.2], p = 0.323) were observed. Acetabular retroversion and overcoverage groups showed higher APP-PT compared to the control group (both p < 0.05) and were the only diagnoses with significant influence on APP-PT in the stepwise multiple regression analysis. However, all observed differences were below the MCID. Demographic factors age, gender, height, weight and BMI showed no influence on APP-PT.

APP-PT across different hip pathomorphologies showed no clinically significant variation. It does not appear to be a relevant contributing factor in the evaluation of young patients eligible for hip preservation surgery.

To quantify the acetabular coverage of the femoral head, Lequesne's vertical-center-anterior edge (VCA) angle is used on the false profile view. Lateral coverage is determined by Wiberg's lateral-center-edge (LCE) angle on an ap pelvic view. The delimitation of the weightbearing area is defined by the end of the subchondral sclerosis line for both views. To our knowledge the exact anatomic location of the points used for measurement on the acetabular rim are not known.

Six hips from three cadaver pelvises (3 male and 3 female) were investigated. The anterior and lateral points of interested were identified radiographically using fluoroscopy and marked with 1mm ceramic bullets. Standard false profile views and ap pelvic views in neutral inclination and rotation were taken to check the correct location of the ceramic bullets. A CT of each pelvis was made to locate the ceramic bullets and to define the exact anatomic location of the measurement points on the o'clock position. 6 o‘clock was defined as the midpoint between anteroinferior and the posteroinferior rim edges. Values were normalized for a right hip.

The mean clockface location for the VCA was 1:33 (range, 1:15 to 1:40) and for the LCE 0:38 (range, 0:20 to 0:50).

The LCEA is slightly anterior to the 12 o'clock position and remains useful to quantify the lateral coverage. Surprisingly, the point used for measuring the VCA is only about 30° (1h) anterior of the point used for measuring the LCEA. Its value for determining anterior cover has to be questioned. The discrepancy to other studies in the literature is because this study identifies and measures the end of the weight bearing zone, and not the border of the bony acetabulum.

Distal femur fractures (DFF) are common, especially in the elderly and high energy trauma patients. Lateral locked osteosynthesis constructs have been widely used, however non-union and implant failures are not uncommon. Recent literature advocates for the liberal use of supplemental medial plating to augment lateral locked constructs. However, there is a lack of proprietary medial plate options, with some authors supporting the use of repurposing expensive anatomic pre-contoured plates. The aim of this study was to investigate the feasibility of a readily available cost-effective medial implant option.

A retrospective analysis from January 2014 to June 2022 was performed on DFF (primary or revision) managed with supplemental medial plating with a Large Fragment Locking Compression Plate (LCP) T-Plate (~$240 AUD) via a medial sub-vastus approach. The T-plate was contoured and placed superior to the medial condyle. A combination of 4.5mm cortical, 5mm locking and/or 6.5mm cancellous screws were used, with oblique screw trajectories towards the distal lateral cortex of the lateral condyle. All extra-articular fractures and revision fixation cases were allowed to weight bear immediately. The primary outcome was union rate.

This technique was utilised on sixteen patients; 3 acute, 13 revisions; mean age 52 years (range 16-85), 81% male, 5 open fractures. The union rate was 100%, with a median time to union of 29 weeks (IQR 18-46). The mean follow-up was 15 months. There were two complications: a deep infection requiring two debridements and a prominent screw requiring removal. The mean range of motion was 1–108^o.

Supplemental medial plating of DFF with a Large Fragment LCP T-Plate is a feasible, safe, and economical option for both acute fixation and revisions. Further validation on a larger scale is warranted, along with considerations to developing a specific implant in line with these principles.

Aim

There are no studies in literature that analyze the effectiveness of closed-incisional negative pressure wound therapy (ciNPWT) in the treatment of bone and joint infections (BJI). The aim of the study was to evaluate the efficacy and the safety of the application of ciNPWT in the postsurgical wound management of patients with osteoarticular infections.

To determine whether pre-operative cessation of anticoagulant or antiplatelet medication is necessary for patients undergoing total shoulder arthroplasty (TSA) or reverse total shoulder arthroplasty (RTSA).

A prospectively maintained database was used to identify 213 consecutive patients treated with TSA or RTSA performed by a single surgeon across 3 centres. This cohort included 24 patients on an anticoagulant agent (warfarin, apixaban, rivaroxaban, dabigatran), 52 patients on an antiplatelet agent (aspirin, clopidogrel), and a control group of 137 patients not on anticoagulant or antiplatelet medication. Patients on anticoagulant or antiplatelet medications continued these agents peri-operatively. Outcomes included haemoglobin drop, intra-operative blood loss, operative time, transfusion requirements and post-operative complications.

The mean age of the cohort was 74.3 years (range 47 – 93) and 75 (35.2%) of the patients were male. TSA was performed in 63 cases and RTSA in 150 cases. The mean haemoglobin drop in the control group was 17.3 g/L, compared to 19.3 g/L in the anticoagulant group (p = 0.20) and 15.6 g/L in the anti-platelet group (p = 0.14). The mean intra-operative blood loss in the control group was 107.8 mL, compared to 143.0 mL in the anticoagulant group (p = 0.03) and 134.3 mL in the anti-platelet group (0.02). The mean operative time in the control group was 49.3 minutes, compared to 47.1 minutes in the anticoagulant group (p = 0.56) and 50.3 minutes in the anti-platelet group (p = 0.78). Post-operatively no patients developed a wound infection or haematoma requiring intervention. Three patients not on anticoagulant or antiplatelet medication developed pulmonary embolism.

Continuing anticoagulant or antiplatelet medication was associated with higher intra-operative blood loss, but produced no statistically significant differences in haemoglobin drop, operative time, transfusion requirements or post-operative complications. We now do not routinely stop any anticoagulant or antiplatelet medication for patients undergoing total shoulder arthroplasty.

Abstract

Failure of cephalomedullary fixation for proximal femur fractures is an uncommon event associated with significant morbidity to the patient and cost to the healthcare system. This institution changed nailing system from the PFNA (DePuy Synthes) to InterTan (Smith and Nephew) in February 2020. To assess for non-inferiority, a retrospective review was performed on 247 patients treated for unstable proximal femur fractures (AO 31 A2; A3).

Patients were identified through manual review of fluoroscopic images. Stable fracture patterns were excluded (AO 31 A1). Pre/post operative imaging, demographic data, operative time and ASA scores assessed. Internal/external imaging and national joint registry data were reviewed for follow up.

No significant difference was found in overall failure rate of PFNA vs InterTan (4.84% vs 3.23%; p = 0.748). Overall, short nails were more likely to fail by cut-out than long nails (7.5% vs 1.2%; p = 0.015). Nails which failed by varus cut-out had a higher tip/apex distance (TAD) (26.2mm vs 17.0mm; p < 0.001). Of concern, varus cut-out occurred in two InterTan nails with TAD of <25mm. The PFNA enjoyed a shorter operative time for both the short (59.1 vs 71.8 mins; p = 0.022) and long nails (98.8 vs 114.3 mins; p = 0.016) with no difference in 120-day survival rate.

Overall failure rates of the PFNA and InterTan nailing systems were comparable. However, the failure rate of short nails in this study is concerning. Using long nails with a lag screw design for unstable intertrochanteric femoral fractures may reduce failure rates. Cumulative frequency analysis suggests stringent tip-apex distances of less than 21mm may reduce failure rates in lag-screw design cephulomedullary nails. This dataset suggests that unstable intertrochanteric fractures may be more reliably managed with a long cephalomedullary device.

X-Linked Hypophosphataemia (XLH) is a rare, progressive, hereditary phosphate-wasting disorder characterised by excessive activity of fibroblast growth factor 23. The International XLH Registry was established to provide information on the natural history of XLH and impact of treatment on patient outcomes. The cross-sectional orthopaedic data presented are from the first interim analysis.

The XLH Registry (NCT03193476) was initiated in August 2017, aims to recruit 1,200 children and adults with XLH, and will run for 10 years. At the time of analysis (Last Patient In: 30/11/2020; Database Lock: 29/03/2021) 579 subjects diagnosed with XLH were enrolled from 81 hospital sites in 16 countries (360 (62.2%) children, 217 (37.5%) adults, and 2 subjects of unknown age).

Of subjects with retrospective clinical data available, skeletal deficits were the most frequently self-reported clinical problems for children (223/239, 93.3%) and adults (79/110, 71.8%). Retrospective fracture data were available for 183 subjects (72 children, 111 adults); 50 had a fracture (9 children, 41 adults). In children, fractures tended to occur in tibia/fibula and/or wrist; only adults reported large bone fractures. Joint conditions were noted for 46 subjects (6 children, 40 adults). For adults reporting osteoarthritis, knees (60%), hips (42.5%), and shoulders (22.5%) were the most frequently affected joints. Retrospective orthopaedic surgery data were collected for 151 subjects (52 children, 99 adults). Osteotomy was the most frequent surgery reported (n=108); joint replacements were recorded for adults only.

This is the largest set of orthopaedic data from XLH subjects collected to date. Longitudinal information collected during the 10-year Registry duration will generate real-world evidence which will help to inform clinical practice.

Authors acknowledge the contribution of all International XLH Registry Steering Committee members.

A spine compression fracture is a very common form of fracture in elderly with osteoporosis. Injection of polymethyl methacrylate (PMMA) to fracture sites is a minimally invasive surgical treatment, but PMMA has considerable clinical risks. We develop a novel type thermoplastic injectable bone substitute contains the proprietary composites of synthetic ceramic bone substitute and absorbable thermoplastic polymer.

We used thermoplastic biocompatible polymers Polycaproactone (PCL) to encapsulate calcium-based bone substitutes hydroxyapatite (Ca10(PO4)6(OH)2, HA) and tricalcium phosphate (TCP) to form a biodegradable injectable bone composite material. The space occupation ration PCL:HA/TCP is 1:9. After heating process, it can be injected to fracture site by specific instrument and then self-setting to immediate reinforce the vertebral body.

The thermoplastic injection bone substitute can obtain good injection properties after being heated by a heater at 90˚C for three minutes, and has good anti-washout property when injected into normal saline at 37˚C. After three minutes, solidification is achieved. Mechanical properties were assessed using the material compression test system and the mechanical support close to the vertebral spongy bone.

In vitro cytotoxicity MTT assay (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed and no cell cytotoxicity was observed.

In vivo study with three New Zealand rabbits was performed, well bone growth into bone substitute was observed and can maintain good mechanical support after three months implantation.

The novel type thermoplastic injection bone substitute can achieve (a) adequate injectability and viscosity without the risk of cement leakage; (b) adequate mechanical strength for immediate reinforcement and prevent adjacent fracture; (c) adequate porosity for new bone ingrowth; (e) biodegradability. It could be developed as a new option for treating vertebral compression fractures.

Obesity is a common in individuals undergoing arthroplasty, and the potential for weight loss with improved mobility may be expected by some. The aim of this study was 1. determine the proportion that achieved weight loss after hip or knee arthroplasty, and 2. examine the effect of obesity on patient reported outcomes (PROMS) and satisfaction with surgery.

Participants underwent primary TKA or THA between July 2015 and December 2020 and consented to participation in a research database with baseline PROMS, including weight, BMI, Oxford Knee, or Hip Score, and EQ5D. Participants repeated PROMS at 12 months after surgery with additional questions regarding satisfaction with surgery.

3449 patients completed PROMS 1 year after arthroplasty with weight and BMI. There were 1810 THA and 1639 TKA procedures. The mean baseline BMI was higher in TKA (29.8, SD 5.2) compared to THA (27.7, SD 5.0), p=0.001. A higher proportion of TKA were classified as obese class 1 (29% TKA, 19% THA), obese class 2 (11% TKA and 6% THA), and obese class 3 (5% TKA and 2% THA), p=0.001. The mean weight loss after 1 year was 0.4kg and 0.9kg in obese THA subjects and TKA subjects respectively. In the obese >5kg weight loss was achieved in 13% of TKA and 7% of THA (p=0.001). Obese experienced equivalent improvement in Oxford scores, compared to non-obese subjects. Satisfaction with surgery was reported by 95% of THA and 91% of TKA subjects with no significant differences between BMI group grades (p=0.491 THA and p=0.473 TKA).

Preoperative obesity was observed in 44% of TKA and 27% of THA subjects. In the obese only 1 in 10 subjects lost 5kg or more over 12 months. Obese patients experienced equivalent improvements in outcome after arthroplasty and rates of satisfaction with surgery to the non-obese.

Glutamate regulates the expression of apoptosis-related genes and triggers the apoptosis of fibroblasts in rotator cuff tendons. Subacromial bursitis is always accompanied by symptomatic rotator cuff tear (RCT). However, no study has been reported on the presence of glutamate in subacromial bursa and on its involvement of shoulder pain in patients who had RCT. The purposes of this study were to determine whether the glutamate expression in subacromial bursa is associated with the presence of RCT and with the severity of shoulder pain accompanying RCT.

Subacromial bursal tissues were harvested from patients who underwent arthroscopic rotator cuff tendon repair or glenoid labral repair with intact rotator cuff tendon. Glutamate tissue concentrations were measured, using a glutamate assay kit. Expressions of glutamate and its receptors in subacromial bursae were histologically determined. The sizes of RCT were determined by arthroscopic findings, using the DeOrio and Cofield classification. The severity of shoulder pain was determined, using visual analog scale (VAS). Any associations between glutamate concentrations and the size of RCT were evaluated, using logistic regression analysis. The correlation between glutamate concentrations and the severity of pain was determined, using the Pearson correlation coefficient. Differences with a probability <0.05 were considered statistically significant.

Glutamate concentrations showed significant differences between the torn tendon group and the intact tendon group (P = 0.009). Concentrations of glutamate significantly increased according to increases in tear size (P < 0.001). In histological studies, the expressions of glutamate and of its ionotropic and metabotropic receptors have been confirmed in subacromial bursa. Glutamate concentrations were significantly correlated with pain on VAS (Rho=0.56 and P =0.01).

The expression of glutamate in subacromial bursa is significantly associated with the presence of RCT and significantly correlated with its accompanying shoulder pain.

Acknowledgements: This research was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A3A01018955 and 2017R1D1A1B03035232).

ZrN-multilayer coating is clinically well established in total knee arthroplasty [1–3] and has demonstrated significant reduction in polyethylene wear and metal ion release [4,5].

The goal of our study was to analyze the biotribological behaviour of the ZrN-multilayer coating on a polished cobalt-chromium cemented hip stem.

CoCr28Mo6 alloy hip stems with ZrN-multilayer coating (CoreHip®AS) were tested versus an un-coated version. In a worst-case-scenario the stems with ceramic heads have been tested in bovine serum in a severe cement interface debonding condition under a cyclic load of 3,875 N for 15 million cycles. After 1, 3, 5, 10 & 15 million cycles the surface texture was analysed by scanning-electron-microscopy (SEM) and energy-dispersive x-ray (EDX). Metal ion concentration of Co,Cr,Mo was measured by inductively coupled plasma mass spectroscopy (ICP-MS) after each test interval.

Based on SEM/EDX analysis, it has been demonstrated that the ZrN-multilayer coating keeps his integrity over 15 million cycles of severe stem cemented interface debonding without any exposure of the CoCr28Mo6 substrate.

The ZrN-multilayer coated polished cobalt-chromium cemented hip stem has shown a reduction of Co & Cr metal ion release by two orders of a magnitude, even under severe stem debonding and high interface micro-motion conditions.

ZrN-multilayer coating on polished cobalt-chromium cemented hip stems might be a suitable option for further minimisation of Co & Cr metal ion release in total hip arthroplasty. Clinical evidence has to be proven during the next years.

An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA) pathophysiology remains largely unexplored. This study aimed to compare the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF).

Flow cytometric analysis, protein level measurements (ELISA), NEU oxidative burst assays, detection of NEU phagocytosis (pHrodo^TM Green Zymosan Biparticles^TM Conjugate for Phagocytosis), morphological analysis of the SF-derived/synovial tissue NEUs, and cultivation of human umbilical vein endothelial cells (HUVECs) using SF supernatant were used to characterise NEUs functionally/morphologically.

Results: Compared with INF NEUs, KOA NEUs were characterised by a lower expression of CD11b, CD54 and CD64, a higher expression of CD62L, TLR2 and TLR4, and lower production of inflammatory mediators and proteases, except CCL2.

Functionally, KOA NEUs displayed an increased production of radical oxygen species and phagocytic activity compared with INF NEUs. Morphologically, KOA and INF cells displayed different cell sizes and morphology, histological characteristics of the surrounding synovial tissues and influence on endothelial cells. KOA NEUs were further subdivided into two groups: SF containing <10% and SF with 10%–60% of NEUs. Analyses of two KOA NEU subgroups revealed that NEUs with SF <10% were characterised by 1) higher CD54, CD64, TLR2 and TLR4 expression on their surface; 2) higher concentrations of TNF-α, sTREM-1, VILIP-1, IL-1RA and MMP-9 in SFs.

Our findings reveal a key role for NEUs in the pathophysiology of KOA, indicating that these cells are morphologically and functionally different from INF NEUs. Further studies should explore the mechanisms that contribute to the increased number of NEUs and their crosstalk with other immune cells in KOA.

This study was supported by the Ministry of Health of the Czech Republic (NU20-06-00269; NU21-06-00370).

µCT images are commonly analysed to assess changes in bone density and architecture in preclinical murine models. Several platforms provide automated analysis of bone architecture parameters from volumetric regions of interest (ROI). However, segmentation of the regions of subchondral bone to create the volumetric ROIs remains a manual and time-consuming task. This study aimed to develop and evaluate automated pipelines for trabecular bone architecture analysis of mouse proximal tibia subchondral bone.

A segmented dataset involving 62 knees (healthy and arthritic) from 10-week male C57BL/6 mice were used to train a U-Net type architecture, with µCT scans (downsampled) input that output segmentation and bone volume density (BV/TV) of the subchondral trabecular bone. Segmentations were upsampled and used in tandem with the original scans (10µ) as input for architecture analysis along with the thresholded trabecular bone. The analysis considered the manually and U-Net segmented ROIs using two available pipelines: the ITKBoneMorphometry library and CTan (SKYSCAN). The analyses included: bone volume (BV), total volume (TV), BV/TV, trabecular number (TbN), trabecular thickness (TbTh), trabecular separation (TbSp), and bone surface density (BSBV).

There was good agreement for bone measures between the manual and U-Net pipelines utilizing ITK (R=0.88-0.98) and CTan (R=0.91-0.98). ITK and CTan showed good agreement for BV, TV, BV/TV, TbTh and BSBV (R=0.9-0.98). However, a limited agreement was seen between TbN (R=0.73) and TbSb (R=0.59) due to methodological differences in how spacing is evaluated.

This U-Net/ITK pipeline seamlessly automated both segmentation and quantification of the proximal tibia subchondral bone. This automated pipeline allows the analysis of large volumes of data, and its open-source nature may enable the standardization of stereologic analysis of trabecular bone across different research groups.

Contemporary indications for unicompartmental knee replacement (UKR) include bone on bone radiographic changes in the medial compartment with relatively preserved lateral and patellofemoral compartments. The role of MRI in identifying candidates for UKR is commonplace. The aim of this study was to assess the relationship between radiographic and MRI pre-operative grade and outcome following UKR.

A retrospective analysis of medial UKR patients from 2017 to 2021. Inclusion criteria were medial UKR for osteoarthritis with pre-operative and post-operative Oxford Knee Scores (OKS), pre-operative radiographs and MRI.

89 patients were included. Whilst all patients had grade 4 ICRS scores on MRI, 36/89 patients had grade 3 KL radiographic scores in the medial compartment, 50/89 had grade 4 KL scores on the medial compartment. Grade 3 KL with grade 4 IRCS medial compartment patients had a mean OKS change of 17.22 (Sd 9.190) meanwhile Grade 4 KL had a mean change of 17.54 (SD 9.001), with no statistical difference in the OKS change score following UKR between these two groups (p=0.873). Medial bone oedema was present in all but one patient. Whilst lateral compartment MRI ICRS scores ranged from 1 to 4 there was no association with MRI score of the lateral compartment and subsequent change in oxford score (P value 0.458). Patellofemoral Compartment (PFC) MRI ICRS ranged from 0 to 4. There was no association between PFC ICRS score and subsequent change in oxford knee score (P value .276)

Radiographs may under report severity of some medial sided knee osteoarthritis. We conclude that in patients with grade 3 KL score that would normally not be considered for UKR, pre-operative MRI might identify grade 4 ICRS scores and this subset of patients have equivalent outcomes to patients with radiographic Grade 4 KL medial compartment osteoarthritis.

Odontoid fracture of the second cervical vertebra (C2) is the most common spinal fracture type in elderly patients. However, very little is known about the biomechanical fracture mechanisms, but could play a role in fracture prevention and treatment. This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process.

A total of 42 human C2 specimens (14 female and 28 male, 71.5 ± 6.5 years) were scanned via quantitative computed tomography, divided in 6 groups (n = 7) and subjected to combined quasi-static loading at a rate of 0.1 mm/s until fracturing at inclinations of −15°, 0° and 15° in sagittal plane, and −50° and 0° in transverse plane. Bone mineral density (BMD), specimen height, fusion state of the ossification centers, stiffness, yield load, ultimate load, and fracture type according to Anderson and d'Alonzo were assessed.

While the lowest values for stiffness, yield, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences could be observed among the six groups (p = 0.235, p = 0.646, and p = 0.505, respectively). Evaluating specimens with only clearly distinguishable fusion of the ossification centers (n = 26) reveled even less differences among the groups for all mechanical parameters. BMD was positively correlated with yield load (R² = 0.350, p < 0.001), and ultimate load (R² = 0.955, p < 0.001), but not with stiffness (p = 0.070). Type III was the most common fracture type (23.5%).

These biomechanical outcomes indicate that load direction plays a subordinate role in traumatic fractures of the odontoid process in contrast to BMD which is a strong determinant of stiffness and strength. Thus, odontoid fractures appear to result from an interaction between load magnitude and bone quality.

The use of mesenchymal stem cell (MSCs) for intervertebral disc (IVD) regeneration has been extensively explored in the last two decades. MSCs are potent cell types that can be easily and safely harvested due to their abundancy and availability. Moreover, they are characterized by the capacity to differentiate towards IVD cells as well as release growth factors to support resident cell metabolism and recruit local progenitor cells to induce endogenous repair of degenerated IVDs. This talk will outline the characteristics of the main MSC sources and their effect towards IVD regeneration based on available preclinical and clinical evidence. In addition, innovative aspects of MSC-derived cell-free therapies will also be discussed.

The biological understanding for the disease progression osteoarthritis (OA) has uncovered specific biomarkers from either synovial fluid, articular chondrocytes or synoviocytes that can be used to diagnose the disease. Examples of these biomarkers include interleukin-1β (IL-1β) or collagen II fragments (1, 2). In parallel, isolation of chondrocytes or bone marrow derived mesenchymal stromal cells (MSCs) has yielded cell-based strategies that have shown long- term beneficial effects in a specific cohort of patients, specifically in traumatic cartilage lesions (2). This latter finding shows that patient stratification of OA is an important tool to both match patients for a specific treatment and to develop novel therapies, especially disease modifying drugs. In order to create disease stage specific therapies, the use of next generation analysis tools such as RNAseq and metabolomics, has the potential to decipher specific cellular and molecular endotypes. Alongside greater understanding of the clinical phenotype (e.g. imaging, pain, co- morbidities), therapies can be designed to alleviate the symptoms of OA at specific points of the disease in patients. This talk will outline the current biological understanding of OA and discuss how patient stratification could assist in the design of innovative therapies for the disease.

Acknowledgements: This presentation was supported by the COST action, CA21110 – Building an open European Network on Osteoarthritis Research (NetwOArk)

Tip-apex distance (TAD) has long been discussed as a metric for determining risk of failure in fixation of peritrochanteric hip fractures. This study seeks to investigate risk factors including TAD for hospital readmission one year after hip fixation surgery.

A retrospective review of proximal hip fractures treated with single screw intramedullary devices between 2016 and 2020 was performed at a 327 bed regional medical center. Patients included had a postoperative follow-up of at least twelve months or surgery-related complications developing within that time.

44 of the 67 patients in this study met the inclusion criteria with adequate follow-up post-surgery. The average TAD in our study population was 19.57mm and the average one year readmission rate was 15.9%. 3 out of 6 patients (50%) with a TAD > 25mm were readmitted within one year due to surgery-related complications. In contrast, 3 out of 38 patients (7.9%) with a TAD < 25mm were readmitted within one year due to surgery-related complications (p=0.0254). Individual TAD measurements, averaging 22.05mm in patients readmitted within one year of surgery and 19.18mm in patients not readmitted within one year of surgery were not significantly different between the two groups (p=0.2113).

Our data indicate a significant improvement in hospital readmission rates up to one year after hip fixation surgery in patients with a TAD < 25mm with a decrease in readmissions of over 40% (50% vs 7.9%). This result builds upon past investigations by extending the follow-up time to one year after surgery and utilizing hospital readmissions as a metric for surgical success. With the well-documented physical and financial costs of hospital readmission after hip surgery, our study highlights a reduction of TAD < 25mm as an effective method of improving patient outcomes and reducing financial costs to patients and medical institutions.

Osteoarthritis (OA) is the most common degenerative joint disorder. Its multifactorial etiology includes age, sex, joint overloading, genetic or nervous influences. In particular, the autonomic nervous system is increasingly gaining in importance. Its two branches, the sympathetic (SNS) and parasympathetic nervous system, are well-balanced under healthy conditions. OA patients seem to be prone to an autonomic imbalance and therefore, we analyzed their autonomic status.

More than 200 participants including patients with early and late stage knee OA (before and 1 year after knee replacement surgery) and healthy probands (age-matched) were analyzed. Heart rate variability was measured via electrocardiogram to assess long-term sympathetic (low-frequency=LF) and parasympathetic (high-frequency=HF, pRR50) activities or general variability (RMSSD, SDRR). Serum cortisol concentrations were measured by ELISA. Perceived chronic stress (PSQ) was assessed via questionnaire. Multivariant regression was performed for data analysis. LF/HF value of early OA was slightly increased compared to healthy controls but significantly higher compared to late OA patients before (p>0.05) and after TKR (p>0.01). HF in late OA patients before TKR was significantly decreased compared to patients after TKR (p>0.001) or healthy controls (p>0.05). Healthy probands exhibited the highest SDRR values, early OA patients had slightly lower levels and late OA patients before TKR displayed significantly reduced SDRR (p>0.001). The same differences were observed in pRR50 and RMSSD. Serum cortisol concentrations and PSQ scores increased in late OA patients before TKR. At the time point of TKR, women with beta blocker medication had significantly higher age (71 ± 9 years) than those without (63 ± 12 years)(p>0.01). An autonomic dysfunction with sympathetic dominance occurs in OA patients. The fact that beta blocker medication in women delayed the need of TKR indicates that SNS inhibition might counteract OA. Future therapeutic interventions for OA should consider a systemic approach with special regard on the ANS.

Translational models for OA have used a variety of small (mouse, rat) and large (sheep, pig) animal models to evaluate the efficacy of a specific therapy. Clinical trials based on the results of these animal models have yielded mixed results with respect to the treatment of the disease. Due to greater stringency in EU regulations in the use of animal models for research, ex vivo models of OA (e.g. cartilage explants, bioreactors) are being developed to mimic human joint motion as well as the inflammatory milieu (e.g. IL-1β) that can be used to understand efficacy of therapy in a physiological environment. The development of these models can enable therapies to undergo clinical trials in patients without the necessity for long-term animal studies. This presentation will describe the state of the art in this field and will discuss whether there is potential to speed up translation from bench to bedside in the future.

The HIPGEN study funded under EU Horizon 2020 (Grant 7792939) has the aim to investigate the potential of the first regenerative cell therapy for the improvement of recovery after muscle injury in hip fracture patients. For this aim we intramuscularly injected placental derived mesenchymal stromal cells during hip fracture arthroplasty. Despite not having reached the primary endpoint, which was the Short Physical Performance Battery, we could observe an increase in abductor muscle strength and a faster return to balance looking at symmetry in insole measurements during follow up.

To investigate changes in quadriceps and hamstrings muscle groups during sustained isokinetic knee flexion and extension.

125 paediatric participants (45 males and 80 females, mean age 14.2 years) were divided into two groups: participants with a confirmed ACL tear (ACLi, n = 64), and puberty- and activity-level matched control participants with no prior history of knee injuries (CON, n = 61). Participants completed a series of 44 repetitions of isokinetic knee flexion and extension at 90 deg/ sec using a Biodex dynamometer (Biodex Medical Systems Inc, Shirley, New York). Surface EMG sensors (Delsys Incorporated, Natick, MA) simultaneously recorded the quadriceps and hamstring activations. Muscle function was assessed as the change in quadriceps activation and extension torque were calculated using the percent difference between the mean of the first five trials, and the mean of the last five trials.

ACLi participants had significantly higher percent change in quadriceps activation for both healthy and injured legs, in comparison to CON dominant leg. As such, the healthy leg of the ACLi participants is activating significantly more than their health matched controls, while also demonstrating reduced muscular endurance (less torque in later repetitions). Therefore, we conclude that the non-injured limb of the ACLi participant is not performing as a healthy limb. Since return to activity clearance following ACLi implies return to sport against age- and activity matched opponents, clearing young athletes based on the non-injured contralateral limb may put them at greater risk of reinjury.

Bone regeneration is a complex but very well organized process in which the immune system has a decisive role. The adaptive immune system and its experience level (percentage of effector and memory T cells) has been proven to influence the healing cascade especially in the early healing phases. This opens the possibility of an early intervention to enhance bone healing during the primary clinical treatment. Patients stratified for possible delayed bone healing could benefit from immunomodulatory treatment approaches. In pre-clinical studies cells and signaling molecules have been identified that could represent promising candidates to help patients in need.

To describe clinical situations for use of modified VAC in POC based on: diagnosis, comorbidities, BMI, wound size in cm, days following trauma when VAC was first applied, total duration of uninterrupted use, frequency of change, settings, bacterial growth, outcomes

To report the outcomes of mVAC use in POC within 6 months to help improve and standardize its application in the institution

This study involves data gathering from inpatients handled by orthopedic surgeons in training and subspecialty rotations in POC. The data collected are highly dependent on the doctors-in-charge's complete charting, thorough reporting and accurate documentation. Modified Vacuum Assisted Closure (mVAC) is used frequently in this study and is defined as a form of revised, adapted and reformed use of VAC based on available materials in the involved institution. The materials that are included are, but not limited to the following: sterile Uratex™ blue foam, nasogastric or suction tubing, phlegm suction machine, Bactigras™ and Opsite™ or Ioban™.

A total of 58 patients were included in the study. The average age of the population was 35 and are predominantly male. The most common mechanism of injury was motorcycle accident and 37 of the patients were diagnosed with an open fracture of the lower extremity with open tibia fractures (22) being the most common. Average wound area measured was 24.12 cm³. All patients yield a bacteria growth with e. coli being the most frequent. Average during of uninterrupted use was 39 days. Of the 58 included in the study, 8 patients underwent STSG, 2 had a flap coverage surgery, 4 patients eventually underwent amputation and 33 with complete resolution of soft tissue defect after conversion to biologic dressing post-mVAC. The rest of the population were still ongoing mVAC at the end of the study.

mVAC is an alternative temporary medium for soft tissue coverage for cases with or without concomitant fractures. mVAC promotes removal of exudate from the wound, supports wound apposition and granulation bed proliferation. Usage mVAC helps prepare for skin coverage procedure and on some cases leads to full resolution of defect.

The rotator cuff tendinopathy is one of the most common shoulder problems leading to full-thickness rotator cuff tendon tear and, eventually, to degenerative arthritis. Recent research on rotator cuff tendon degeneration has focused on its relationship to cell death. The types of cell death known to be associated with rotator cuff tendon degeneration are apoptosis, necrosis, and autophagic cell death. The increased incidence of cell death in degenerative tendon tissue may affect the rates of collagen synthesis and repair, possibly weakening tendon tissue and increasing the risk of tendon rupture. The biomolecular mechanisms of the degenerative changes leading to apoptotic cell death in rotator cuff tenofibroblasts have been identified as oxidative-stress-related cascade mechanisms. Furthermore, apoptosis, necrosis, and autophagic cell death are all known to be mediated by oxidative stress, a condition in which ROS (reactive oxygen species) are overproduced. Lower levels of oxidative stress trigger apoptosis; higher levels mediate necrosis. Although the signaltransduction pathway leading to autophagy has not yet been fully established, ROS are known to be essential to autophagy. A neuronal theory regarding rotator cuff degeneration has been developed from the findings that glutamate, a neural transmitter, is present in increased concentrations in tendon tissues with tendinopathy and that it induces rat supraspinatus tendon cell death. Recent studies have reported that hypoxia involved in rotator cuff tendon degeneration. Because antioxidants are known to scavenge for intracellular ROS, some studies have been conducted to determine whether antioxidants can reduce cell death in rotator cuff tendon-origin fibroblasts. The first study reported that an antioxidant has the ability to reduce apoptosis in oxidative-stressed rotator cuff tenofibroblasts. The second study reported that antioxidants have both antiapoptotic effects and antinecrotic effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The third study reported that an antioxidant has antiautophagic-cell-death effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The fourth study reported that glutamate markedly increases cell death in rotator cuff tendonorigin fibroblasts. The glutamate-induced cytotoxic effects were reduced by an antioxidant, demonstrating its cytoprotective effects against glutamate-induced tenofibroblast cell death. The fifth study reported that hypoxia significantly increases intracellular ROS and apoptosis. The hypoxia-induced cytotoxic effects were markedly attenuated by antioxidants, demonstrating their cytoprotective effects against hypoxia-induced tenofibroblast cell death. In conclusion, antioxidants have cytoprotective effects on tenofibroblasts exposed in vitro to an oxidative stressor, a neurotransmitter, or hypoxia. These cytoprotective effects result from antiapoptotic, antinecrotic, and antiautophagic actions involving the inhibition of ROS formation. These findings suggest that antioxidants may have therapeutic potential for rotator cuff tendinopathy. Further studies must be conducted in order to apply these in vitro findings to clinical situations.

Osteoarthritis (OA) is the most common joint disease, affecting approximately 16% of the adult population worldwide. The chronic inflammation in the joint leads to the breakdown of cartilage, which leads to permanent pain and limitations in everyday life at an early stage of the disease. To date, there is no therapy that can interrupt the inflammatory state or reverse cartilage damage. The PROTO consortium (funded by the EU Horizon Europe program, Grant 101095635) aims to prevent the development of OA by correcting a pathological biomechanical pattern by a digital training intervention and to treat early stage OA with an innovative allogeneic cell therapy.

More and more evidences showed that cartilage harbored local progenitor cells that could differentiate toward osteoblast, chondrocyte, and adipocyte. However, our previous results showed that osteoarthritis derived chondroprogenitor cells (OA-CPC) exhibited strong osteogenic potential even in chondrogenic condition. How to promote their chondrogenic potential is the key for cartilage repair and regeneration in osteoarthritis. Recently, lipid availability was proved to determine skeletal progenitor fate. Therefore, we aim to determine whether lipid inhibition under 3D culture condition could enhance OA-CPC chondrogenesis. Moreover, glucose concentration was also evaluated for chondrogenic capacity. Although there are many researches showed that lower glucose promotes chondrogenesis, in our results, we found that OA-CPC in high concentration of glucose (4.5g/L) with lipid inhibitor (GW1100) showed strongest chondrogenic potential, which could form largest cell pellet with strong proteoglycan staining, COL II expression and no COL I expression. Besides, COL2A1 was increased and COL10A1 was decreased significantly by GW1100 under high glucose condition in 2D culture. Interestingly, although the expression level of MMP13 was not changed by GW1100 at RNA and protein level, less MMP13 protein secreted out of cell nuclear. In summary, we estimated that higher glucose and lower lipid supplies benefit OA-CPC chondrogenesis and cartilage repair.

Knee joint distraction (KJD) has been associated with clinical and structural improvement and synovial fluid (SF) marker changes. However, structural changes have not yet been shown satisfactorily in regular care, since radiographic acquisition was not fully standardized. AI-based modules have shown great potential to reduce reading time, increase inter-reader agreement and therefore function as a tool for treatment outcome assessment. The objective was to analyse structural changes after KJD in patients using this AI-based measurement method, and relate these changes to clinical outcome and SF markers.

20 knee OA patients (<65 years old) were included in this study. KJD treatment was performed using an external fixation device, providing 5 mm distraction for 6 weeks. SF was aspirated before, during and immediately after treatment. Weight-bearing antero-posterior knee radiographs and WOMAC questionnaires were collected before and ~one year after treatment. Radiographs were analysed with the Knee Osteoarthritis Labelling Assistant (KOALA, IB Lab GmbH, Vienna, Austria), and 10 pre-defined biomarker levels in SF were measured by immunoassay. Radiographic one-year changes were analysed and linear regression was used to calculate associations between changes in standardized joint space width (JSW) and WOMAC, and changes in JSW and SF markers.

After treatment, radiographs showed an improvement in Kellgren-Lawrence grade in 7 of 16 patients that could be evaluated; 3 showed a worsening. Joint space narrowing scores and continuous JSW measures improved especially medially. A greater improvement in JSW was significantly associated with a greater improvement in WOMAC pain (β=0.64;p=0.020). A greater increase in MCP1 (β=0.67;p=0.033) and lower increase in TGFβ1 (β=-0.787;p=0.007) were associated with JSW improvement.

Despite the small number of patients, also in regular care KJD treatment shows joint repair as measured automatically on radiographs, significantly associated with certain SF marker change and even with clinical outcome.

3D accurate measurements of the skeletal structures of the foot, in physiological and impaired subjects, are now possible using Cone-Beam CT (CBCT) under real-world loading conditions. In detail, this feature allows a more realistic representation of the relative bone-bone interactions of the foot as they occur under patient-specific body weight conditions. In this context, varus/valgus of the hindfoot under altered conditions or the thinning of plantar tissues that occurs with advancing age are among the most complex and interesting to represent, and numerous measurement proposals have been proposed. This study aims to analyze and compare these measurements from CBCT in weight-bearing scans in a clinical population. Sixteen feet of diabetic patients and ten feet with severe adult flatfoot acquired before/after corrective surgery underwent CBCT scans (Carestream, USA) while standing on the leg of interest. Corresponding 3D shapes of each bone of the shank and hindfoot were reconstructed (Materialise, Belgium). Six different techniques found in the literature were used to calculate the varus/valgus deformity, i.e., the inclination of the hindfoot in the frontal plane of the shank, and the distance between the ground and the metatarsal heads was calculated along with different solutions for the identification of possible calcifications. Starting with an accurate 3D reconstruction of the skeletal structures of the foot, a wide range of measurements representing the same angle of hindfoot alignment were found, some of them very different from each other. Interesting correlations were found between metatarsal height and subject age, significant in diabetic feet for the fourth and fifth metatarsal bones. Finally, CBCT allows 3D assessment of foot deformities under loaded conditions. The observed traditional measurement differences and new measurement solutions suggest that clinicians should consider carefully the anatomical and functional concepts underlying measurement techniques when drawing clinical and surgical conclusions.

In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription. The ratio of M2 markers (CD206 or CD163) to M1 markers (CD38) increased when MSCs were added to Mo/M1 macrophages, regardless of culture system used (direct or indirect). Pro-inflammatory markers (including TNFβ) decreased. CXCR2 expression by both M1 macrophages and MSCs decreased when MSCs were added to differentiated M1 macrophages in transwell. When adding initially M1 CM (for 12 hours) followed by M2 CM (for 12 hours) sequentially to chondrocytes, there was a significant increase of Aggrecan and Collagen type 2 gene expression and decrease in fibroblastic cell surface markers (PDPN/CD90). Mo/M1 macrophages cultured with MSCs, directly or indirectly, are shifted towards a more M2 phenotype. Indirect culture suggests this effect can occur via soluble signaling mediators. Sequential exposure of M1CM followed by M2CM to chondrocytes resulted in increased chondrogenic and reduced fibrotic gene expression, suggesting that an acute pro-inflammatory stimulus may prime chondrocytes before repair.

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence.

Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated.

The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells.

Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection.

Introduction

With advances in mobile application, digital health is being increasingly used for remote and personalised care. Patient education, self-management and tele communication is a crucial factor in optimising outcomes.

BACKGROUND

Theatre-listed trauma patients routinely require two ‘group and save’ blood-bank samples, in case they need perioperative transfusion. The Welsh Blood Service (WBS) need patients to have one recorded sample from any time in the last 10 years. A second sample, to permit cross-matching and blood issuing, must be within 7 days of transfusion (or within 48 hours if the patient is pregnant, or has been transfused within the last 3 months). The approximate cost of processing a sample is £15.00.

Results in patients undergoing total hip arthroplasty (THA) for femoral head osteonecrosis (ON) when compared with primary osteoarthritis (OA) are controversial. Different factors like age, THA type or surgical technique may affect outcome. We hypothesized that patients with ON had an increased revision rate compared with OA. We analysed clinical outcome, estimated the survival rate for revision surgery, and their possible risk factors, in two groups of patients.

In this retrospective cohort analysis of our prospective database, we assessed 2464 primary THAs implanted between 1989 and 2017. Patients with OA were included in group 1, 2090 hips; and patients with ON in group 2, 374 hips. In group 2 there were more men (p<0.001), patients younger than 60 years old (p<0.001) and with greater physical activity (p<0.001). Patients with lumbar OA (p<0.001) and a radiological acetabular shape type B according to Dorr (p<0.001) were more frequent in group 1. Clinical outcome was assessed according to the Harris Hip Score and radiological analysis included postoperative acetabular and femoral component position and hip reconstruction. Kaplan-Meier survivorship analysis was used to estimate the cumulative probability of not having revision surgery for different reasons. Univariate and multivariate Cox regression models were used to assess risk factors for revision surgery.

Clinical improvement was better in the ON at all intervals. There were 90 hips revised, 68 due to loosening or wear, 52 (2.5%) in group 1, and 16 (4.3%) in group 2. Overall, the survival rate for revision surgery for any cause at 22 years was 88.0 % (95% CI, 82-94) in group 1 and 84.1% (95% CI, 69 – 99) in group 2 (p=0.019). Multivariate regression analysis showed that hips with conventional polyethylene (PE), compared with highly-cross linked PEs or ceramic-on-ceramic bearings, (p=0.01, Hazard Ratio (HR): 2.12, 95% CI 1.15-3.92), and cups outside the Lewinnek´s safe zone had a higher risk for revision surgery (p<0.001, HR: 2.57, 95% CI 1.69-3.91).

Modern highly-cross linked PEs and ceramic-on-ceramic bearings use, and a proper surgical technique improved revision rate in patients undergoing THA due to ON compared with OA.

The current procedures being applied in the clinical setting to address osteoporosis-related delayed union and nonunion bone fractures have been found to present mostly suboptimal outcomes. As a result, bone tissue engineering (BTE) solutions involving the development of implantable biomimetic scaffolds to replace damaged bone and support its regeneration are gaining interest. The piezoelectric properties of the bone tissue, which stem primarily from the significant presence of piezoelectric type I collagen fibrils in the tissue's extracellular matrix (ECM), play a key role in preserving the bone's homeostasis and provide integral assistance to the regeneration process. However, despite their significant potential, these properties of bone tend to be overlooked in most BTE-related studies. In order to bridge this gap in the literature, novel hydroxyapatite (HAp)-filled osteoinductive and piezoelectric poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TrFE) electrospun nanofibers were developed to replicate the bone's fibrous ECM composition and electrical features. Different HAp nanoparticle concentrations (1–10%, wt%) were tested to assess their effect on the physicochemical and biological properties of the resulting fibers. The fabricated scaffolds displayed biomimetic collagen fibril-like diameters, while also presenting mechanical features akin to type I collagen. The increase in HAp presence was found to enhance both surface and piezoelectric properties of the fibers, with an improvement in scaffold wettability and increase in β-phase nucleation (translating to increased piezoelectricity) being observed. The HAp-containing scaffolds also exhibited an augmented bioactivity, with a more comprehensive surface mineralization of the fibers being obtained for the scaffolds with the highest HAp concentrations. Improved osteogenic differentiation of seeded human mesenchymal stem/stromal cells was achieved with the addition of HAp, as confirmed by an increased ALP activity, calcium deposition and upregulated expression of key osteogenic markers. Overall, our findings highlight, for the first time, the potential of combining PVDF-TrFE and HAp to develop electroactive and osteoinductive nanofibers for BTE.

Acknowledgements: The authors thank FCT for funding through the projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), OptiBioScaffold (PTDC/EME-SIS/4446/2020) and BioMaterARISES (EXPL/CTM-CTM/0995/2021), the PhD scholarship (2022.10572.BD) and to the research institutions iBB (UIDB/04565/2020 and UIDP/04565/2020) and Associate Laboratory i4HB (LA/P/0140/2020).

Aims

We studied the outcomes following arthroscopic primary repair of bucket handle meniscus tears to determine the incidence of re-tears and the functional outcomes of these patients.

Gait measurements can vary due to various intrinsic and extrinsic factors, and this variability becomes more pronounced using inertial sensors in a free-living environment. Therefore, identifying and quantifying the sources of variability is essential to ensure measurement reliability and maintain data quality.

This study aimed to determine the variability of daily accelerations recorded by an inertial sensor in a group of healthy individuals. Ten participants, four males and six females, with a mean age of 50 years (range: 29–61) and BMI of 26.9 kg/m² (range: 21.4–36.8), were included. A single accelerometer continuously recorded lower limb accelerations over two weeks. We extracted and analyzed the accelerations of three consecutive strides within walking bouts if the time difference between the bouts was more than two hours. Multivariate mixed-effects modeling was performed on both the discretized acceleration waveforms at 101 points (0–100) and the harmonics of the signals in the frequency domain to determine the variance components for different subjects, days, bouts, and steps as the random effect variables. Intraclass correlation coefficients (ICCs) were calculated for between-day, between-bout, and between-step comparisons.

The results showed that the ICCs for the between-day, between-bout, and between-step comparisons were 0.73, 0.82, 0.99 for the vertical axis; 0.64, 0.75, 0.99 for the anteroposterior axis; and 0.55, 0.96, 0.97 for the mediolateral axis. For the signal harmonics, the respective ICCs were 0.98, 0.98, 0.99 for the vertical axis; 0.54, 0.93, 0.98 for the anteroposterior axis; and 0.69, 0.78, 0.95 for the mediolateral axis.

Overall, this study demonstrated that accelerations recorded continuously for multiple days in a free-living environment exhibit high variability, mainly between days, and some variability arising from differences between walking bouts during different times within days. However, reliable and repeatable gait measurements can be obtained by identifying and quantifying the sources of variability.

The use of implant biomaterials for prosthetic reconstructive surgery and osteosynthesis is consolidated in the orthopaedic field, improving the quality of life of patients and allowing for healthy and better ageing. However, there is the lack of advanced innovative methods to investigate the potentialities of smart biomaterials, particularly for the study of local effects of implant and osteointegration. Despite the complex process of osseointegration is difficult to recreate in vitro, the growing challenges in developing alternative models require to set-up and validate new approaches. Aim of the present study is to evaluate an advanced in vitro tissue culture model of osteointegration of titanium implants in human trabecular bone. Cubic samples (1.5×1.5 cm) of trabecular bone were harvested as waste material from hip arthroplasty surgery (CE AVEC 829/2019/Sper/IOR); cylindrical defects (2 mm Ø, 6 mm length) were created, and tissue specimens assigned to the following groups: 1) empty defects- CTR-; 2) defects implanted with a cytotoxic copper pin (Merck cod. 326429)- CTR+; 3) defects implanted with standard titanium pins of 6 µm-rough (ZARE S.r.l) -Ti6. Tissue specimens were cultured in mini rotating bioreactors in standard conditions, weekly assessing viability. At the 8-week-timepoint, immunoenzymatic, microtomographic, histological and histomorphometric analyses were performed. The model was able to simulate the effects of implantation of the materials, showing a drop in viability in CTR+, differently from Ti6 which appears to have a trophic effect on the bone. MicroCT and histological analysis supported the results, with lower BV/TV and Tb.Th values observed in CTR- compared to CTR+ and Ti6 and signs of matrix and bone deposition at the implant site. The collected data suggest the reliability of the tested model which can recreate the osseointegration process in vitro and can therefore be used for preliminary evaluations to reduce and refine in vivo preclinical models.

Acknowledgment: This work was supported by Emilia-Romagna Region for the project “Sviluppo di modelli biologici in vitro ed in silico per la valutazione e predizione dell'osteointegrazione di dispositivi medici da impianto nel tessuto osseo”

Chronic low back pain (CLBP) is the most common cause of disability worldwide, and lumbar spine fusion (LSF) is often chosen to treat pain caused by advanced degenerative disease when clinical treatment failed certain cases, the post-surgical outcomes are not what was expected. Several studies highlight how important are. In psychological variables during the postoperative spine surgery period. The aim of this study is to assess the role of preoperative depression on postoperative clinical outcomes. We included patients who underwent LSF since December 2021. Preoperative depression was assessed administering Beck Depression Inventory questionnaire (BDI). And pain and disability were evaluated at 1, 3, and 6 months, administering respectively Visual Analogic Scale (VAS) and Oswestry Disability Index (ODI). As statistical analysis Mann-Whitney test was performed. We included 46 patients, 20 female (43,5%) and 26 male (56,5%) with an average age of 64,2. The population was divided in two groups, fixing the BDI cut-off point at 10. Patients with BDI < 10 points (N=28) had normal mental health status, instead patients with BDI > 10 points (N=16) had depressive disorders. At 3 months patients with healthy mental status reported statistically significant reduction of pain (U = 372,5, p = .006) and improvement of disability but without statistical significancy (U = 318, p = 0,137). At 6 months patients without psychological disease reported statistically significant reduction of pain (U = 342, p = 0,039) and disability (U = 372,5, p = 0,006).

This study demonstrates the correlation between pre-existing depressive state and poorer clinical outcomes after spine surgery. These results are consistent with the literature. Therefore, during the surgical decision making it is crucial to take psychological variables into account in order to predict the results after surgery and inform patients on the potential influence of mental status.

Introduction

Perception of ACL injury prevention programs amongst professional netball players and coaches has not been studied. We investigated (1) level of awareness and experience of ACL injury prevention programs; (2) use of ACL injury prevention programs; and (3) barriers to implementing ACL injury prevention program in netball.

Herein we address, hyaline cartilage regeneration issue by engineering a synthetic biocompatible hydrogel scaffold capable to promote chondrogenic differentiation. In this study, the chemically crosslinked hydrogels consisting of synthetic peptides that have the collagen-like sequence Cys-Gly-(Pro-Lys-Gly)4 (Pro-Hyp-Gly)4 (Asp-Hyp-Gly)4- conjugated with RGD sequence (CLP-RGD) and crosslinked hydrogels of type I collagen (CA) were used. For cartilage formation, we used human skeletal muscle-derived stem/progenitor cells (hMDSPCs) set for differentiation towards a chondrogenic lineage by BMP-7 and TGF-ß3 growth factors.

Initially 150, 100 and 75 ng of BMP-7and TGF-ß3 growth factors were inserted in each scaffold and amount of growth factors diffusing out of the scaffolds was observed by ELISA assays. In vitro experiments were performed by seeding hMDSPCs onto hydrogels loaded with growth factors (75ng/scaffold) and cultured for 28 days. Cartilage formation was monitored by ELISA and RT-PCR assays. All experiments were performed in triplicates or quadruplicates.

Growth factors incorporation strategy allowed a sustained release of TGF-ß3 growth factor, 6.00.3% of the initially loaded amount diffused out after 4 h and 2.70.5% already at the second time point (24h) from CA and CLP-RGD substrates. For the BMP-7 growth factor, 13.12.3% and 15.751.6% of the initially loaded amount diffused out after 4 h, 1.70.2% and 2.450.3% at the second time point (24 h) from CA and CLP-RGD respectively. In vitro experiments shown that scaffolds with immobilized growth factors resulted in higher collagen type II accumulation when compared to the scaffolds alone. The gene expression on CLP-RGD hydrogels with growth factors has shown lower collagen type I expression and higher aggrecan expression compared to day 0. However, we also report increased collagen X gene expression on CA hydrogels (with growth factors).

Our results support the potential of the strategy of combining hydrogels functionalized with differentiation factors toward improving cartilage repair.

Spontaneous muscle regenerative potential is limited, as severe injuries incompletely recover and result in chronic inflammation. Current therapies are restricted to conservative management, not providing a complete restitutio ad integrum; therefore, alternative therapeutic strategies are welcome, such as cell-based therapies with stem cells or Peripheral Blood Mononuclear Cells (PBMCs). Here, we described two different in vitro myogenic models: a 2D perfused system and a 3D bioengineered scaffold within a perfusion bioreactor. Both models were assembled with human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and human primary skeletal myoblasts (hSkMs) to study induction and maintenance of myogenic phenotype in presence of PBMCs. When hBM-MSCs were cultured with human primary skeletal myoblasts (hSkMs) in medium supplemented with 10 ng/mL of bFGF; cells showed increased expression of myogenic-related gene, such as Desmin and Myosin Heavy Chain II (MYH2) after 21 days, and a prevalent expression of anti-inflammatory cytokines (IL10, 15-fold). Next, PBMCs were added in an upper transwell chamber and hBM-MSCs significantly upregulated myogenic genes throughout the culture period, while pro-inflammatory cytokines (e.g., IL12A) were downregulated. In 3D, hBM-MSCs plus hSkMs embedded in fibrin-based scaffolds, cultured in dynamic conditions, showed that all myogenic-related genes tended to be upregulated in the presence of PBMCs, and Desmin and MYH2 were also detected at protein level, while pro-inflammatory cytokine genes were significantly downregulated in the presence of PBMCs. In conclusion, our works suggest that hBM-MSCs have a versatile myogenic potential, enhanced and modulated by PMBCs. Moreover, our 3D biomimetic approach seemed to better resemble the tissue architecture allowing an efficient in vitro cellular cross-talk.

The aim of this scoping review is to understand the extent and type of evidence in relation to the use of guided growth for correcting rotational deformities of long bones. Guided growth is routinely used to correct angular deformities in long bones in children. It has also been proven to be a viable method to correct rotational deformities, but the concept is not yet fully examined. Databases searched include Medline, Embase, Cochrane Library, Web of Science and Google Scholar.

All identified citations were uploaded into Rayyan.ai and screened by at least two reviewers. The search resulted in 3569 hits. 14 studies were included: 1 review, 3 clinical trials and 10 pre-clinical trials. Clinical trials: a total of 21 children (32 femurs and 5 tibiae) were included. Surgical methods were 2 canulated screws connected by cable, PediPlates obliquely oriented, and separated Hinge Plates connected by FiberTape. Rotation was achieved in all but 1 child. Adverse effects reported include limb length discrepancy (LLD), knee stiffness and rebound of rotation after removal of tethers. 2 pre-clinical studies were ex-vivo studies, 1 using 8-plates on Sawbones and 1 using a novel z-shaped plates on human cadaver femurs. There were 5 lapine studies (2 using femoral plates, 2 using tibial plates and 1 using an external device on tibia), 1 ovine (external device on tibia), 1 bovine (screws and cable on metacarp) and a case-report on a dog that had an external device spanning from femur to tibia. Rotation was achieved in all studies. Adverse effects reported include implant extrusions, LLD, articular deformities, joint stiffness and rebound. All included studies conclude that guided growth is a viable treatment for rotational deformities of long bones, but there is great variation in models and surgical methods used, and in reported adverse effects.

Current evidence suggests that superior surgical team performance is linked to fewer intra-operative errors, reductions in mortality and even improved patient outcomes. Virtual reality has demonstrated excellent efficacy in training surgeons and scrub nurses individually, however its impact on training teams is currently unknown. This study aimed to assess if training together (scrub nurse and surgeon) in an innovative multiplayer virtual reality program was superior to single player training for novices learning anterior approach total hip arthroplasty (AA-THA).

40 participants (20 novice surgeons (CT1-ST3 level) and 20 novice scrub nurses) were enrolled in this study and randomised to individual or team virtual reality training. Individually-trained participants played with virtual avatar counterparts, whilst teams trained live in pairs (surgeon and scrub nurse). Both groups underwent 5 VR training sessions over 6 weeks. Subsequently, they underwent a real-life assessment in which they performed AA-THA on a high-fidelity model with real equipment in a simulated operating theatre. Teams performed together and individually-trained participants were randomly paired up with a solo player of the opposite role. Videos of the assessment were marked by two blinded expert assessors. The primary outcome was team performance as graded by the validated NOTECHs II score. Secondary outcomes were procedure time and number of technical errors from an expert pre-defined protocol.

Teams outperformed individually-trained participants for non-technical skills in the real-world assessment (NOTECHS-II score 50.3 ± 6.04 vs 43.90 ± 5.90, p=0.0275). They completed the assessment 28.1% faster (31.22 minutes ±2.02 vs 43.43 ±2.71, p=0.01), and made close to half the number of technical errors when compared to the individual group (12.9 ± 8.3 vs 25.6 ± 6.1, p=0.001).

Multiplayer, team training appears to lead to faster surgery with fewer technical errors and the development of superior non-technical skills.

Cell culture on tissue culture plastic (TCP) is widely used across biomedical research to understand the in vivo environment of a targeted biological system. However, growing evidence indicates that the characteristics of cells investigated in this way differ substantially from their characteristics in the human body. The limitations of TCP monolayer cell cultures are especially relevant for chondrocytes, the cell population responsible for producing cartilage matrix, because their zonal organization in hyaline cartilage is not preserved in a flattened monolayer assay. Here, we contrast the response of primary human chondrocytes to inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma, via transcriptional, translational, and histological profiling, when grown either on TCP or within a 3D cell pellet (scaffold-less). We focus on anti-apoptotic (Bcl2), pro-apoptotic (Bax, Mff, Fis1), and senescent (MMP13, MMP1, PCNA, p16, p21) markers. We find that the 3D environment of the chondrocyte has a profound effect on the behavior and fate of the cell; in TCP monolayer cultures, chondrocytes become anti-apoptotic and undergo senescence in response to inflammatory cytokines, whereas in 3D cell pellet cultures, they exhibit a pro-apoptotic response. Our findings demonstrate that chondrocyte culture environment plays a pivotal role in cell behavior, which has important implications for the clinical applicability of in vitro research of cartilage repair. Although there are practical advantages to 2D cell cultures, our data suggest researchers should be cautious when drawing conclusions if they intend to extrapolate findings to in vivo phenomena. Our data demonstrates opposing chondrocyte responses in relation to apoptosis and senescence, which appear to be solely reliant on the environment of the culture system. This biological observation highlights that proper experimental design is crucial to increase the clinical utility of cartilage repair experiments and streamline their translation to therapy development.

Stimulation of the mechanosensitive ion channel, Piezo1 promotes bone anabolism and SNPs in the Piezo1 locus are associated with changes in fracture risk. Osteocytes function as critical regulators of bone homeostasis by sensing mechanical signals. The current study used a human, cell-based physiological, 3D in vitro model of bone to determine whether loading of osteocytes in vitro results in upregulation of the Piezo1 pathway.

Human Y201 MSCs, embedded in type I collagen gels and differentiated to osteocytes for 7-days, were subjected to pathophysiological load (5000 µstrain, 10Hz, 5 mins; n=6) with unloaded cells as controls (n=4). RNA was extracted 1-hr post load and assessed by RNAseq analysis. To mimic mechanical load and activate Piezo1, cells were differentiated to osteocytes for 13 days and treated ± Yoda1 (5µM, 2- and 24-hs, n=4); vehicle treated cells served as controls (n=4). RNA was subjected to RT-qPCR and data normalised to the housekeeping gene, YWHAZ. Media was analysed for IL6 release by ELISA.

Mechanical load upregulated Piezo1 gene expression (16.5-fold, p<0.001) and expression of the transcription factor NFATc1, and matricellular protein CYR61, known regulators of Piezo1 mechanotransduction (3-fold; p= 5.0E-5 and 6.8-fold; p= 6.0E-5, respectively). After 2-hrs, Yoda1 increased the expression of the early mechanical response gene, cFOS (11-fold; p=0.021), mean Piezo1 expression (2.3-fold) and IL-6 expression (103-fold, p<0.001). Yoda1 increased the release of IL6 protein after 24 hours (7.5-fold, p=0.001).

This study confirms Piezo1 as an important mechanosensor in osteocytes. Piezo1 activation mediated an increase in IL6, a cytokine that drives inflammation and bone resorption providing a direct link between mechanical activation of Piezo1, bone remodeling and inflammation, which may contribute to mechanically induced joint degeneration in diseases such as osteoarthritis. Mechanistically, we hypothesize this may occur through promoting Ca2+ influx and activation of the NFATc1 signaling pathway.

Standard fixation for intra-articular distal humerus fracture is open reduction and internal fixation (ORIF). However, high energy fractures of the distal humerus are often accompanied with soft tissue injuries and or vascular injuries which limits the use of internal fixation. In our report, we describe a highly complex distal humerus fracture that showed promising healing via a ring external fixator.

A 26-year-old man sustained a Gustillo Anderson Grade IIIB intra-articular distal humerus fracture of the non-dominant limb with bone loss at the lateral column. The injury was managed with aggressive wound debridement and cross elbow stabilization via a hinged ring external fixator. Post operative wound managed with foam dressing. Post-operatively, early controlled mobilization of elbow commenced. Fracture union achieved by 9 weeks and frame removed once fracture united. No surgical site infection or non-union observed throughout follow up. At 2 years follow up, flexion - extension of elbow is 20°- 100°, forearm supination 65°, forearm pronation 60° with no significant valgus or varus deformity.

The extent of normal anatomic restoration in elbow fracture fixation determines the quality of elbow function with most common complication being elbow stiffness. Ring fixator is a non-invasive external device which provides firm stabilization of fracture while allowing for adequate soft tissue management. It provides continuous axial micro-movements in the frame which promotes callus formation while avoiding translation or angulation between the fragments. In appropriate frame design, they allow for early rehabilitation of joint where normal range of motion can be allowed in controlled manner immediately post-fixation.

Functional outcome of elbow fracture from ring external fixation is comparable to ORIF due to better rehabilitation and lower complications. Ring external fixator in our patient achieved acceptable functional outcome and fracture alignment meanwhile the fracture was not complicated with common complications seen in ORIF.

In conclusion, ring external fixator is as effective as ORIF in treating complex distal humeral fractures and should be considered for definitive fixation in such fractures.

The novel, highly-sensitive and non-destructive method for the quantification of the osteogenic potential of bone marrow mesenchymal stem cells (BM-MSCs), by the evaluation of its hydroxyapatite (HA), in vitro is 99mTc-HDP-Labelling. 99mTc-HDP (tracer) binds rapidly to HA and this uptake can be visualized and quantified. This study was performed to evaluate if this method is suitable to perform a real-time assessment during an ongoing cell culture and if the radioactive tracer may influence the cells and their ability to differentiate.

BM-MSCs (n=3) were cultivated in 35mm-dishes. Groups 1 and 3 received DMEM-LG based osteogenic media while Groups 2 und 4 were non-osteogenic controls.

Groups 1 and 2 (multi-labelling) were incubated with 5 MBq 99mTc-HDP for 30min on day 7 (d7) and the bound activity was measured using an activimeter. Subsequently the cell-culture was continued and again labelled with 99mTc-HDP on day 14 and 21 (d14, d21).

Groups 3 and 4 (single labelling), cultivation of the respective triplicates, ended on day 7, 14 and 21 (d7, d14, d21) followed by 99mTc-HDP-Labelling.

Statistical analysis using one-factor ANOVA (p<0.05).

Absolute tracer uptake increased steadily in both osteogenic groups: 1 (d7: 0.315; d14: 1.093; d21: 3.283 MBq) and 3 (d7: 0.208; d14: 0.822; d: 212.437 MBq) and was significantly higher than in the corresponding non-osteogenic control-group (Group 2 and 4) at all timepoints. (p<0.001).

No significant negative effect of the radioactive tracer could be revealed in group 1 (multi radioactive labelling on d7, d14, d21) compared to Group 3 (singe labelling).

The 99mTc-Uptake of groups 2 and 4 was not significantly different at any time.

Our data show that the repeated exposition to 99mTc-HDP has no negative influence on the osteogenic differentiation potential of BM-MSCs. Therefore, the method is capable of determining the amount of HA during an ongoing cell culture.

Our musculoskeletal system has a limited capacity for repair. This has led to increased interest in the development of tissue engineering and biofabrication strategies for the regeneration of musculoskeletal tissues such as bone, ligament, tendon, meniscus and articular cartilage. This talk will demonstrate how different musculoskeletal tissues, specifically cartilage, bone and osteochondral defects, can be repaired using emerging biofabrication and 3D bioprinting strategies. This will include examples from our lab where cells and/or growth factors are bioprinted into constructs that can be implanted directly into the body, to approaches where biomimetic tissues are first engineered in vitro before in vivo implantation. The efficacy of these different biofabrication strategies in different preclinical studies will be reviewed, and lessons from the relative successes and failures of these approaches to tissue regeneration will be discussed.

In an attempt to alleviate symptoms of the disease, patients with knee osteoarthrosis (KOA) frequently alter their gait patterns. Understanding the underlying pathomechanics and identifying KOA phenotypes is essential for improving treatments. We aimed to investigate altered kinematics in patients with KOA to identify subgroups.

Sixty-six patients with symptomatic KOA scheduled for total knee arthroplasty and 12 age-matched healthy volunteers with asymptomatic knees were included. We used k-means to separate the patients based on dynamic radiostereometric assessed knee kinematics. Ligament lesions, KOA score, and clinical outcome were assessed by magnetic resonance imaging, radiographs, and patient reported outcome measures, respectively.

We identified four clusters that were supported by clinical characteristics. Compared with the healthy group; The flexion group (n=20): revealed increased flexion, greater adduction, and joint narrowing and consisted primarily of patients with medial KOA. The abduction group (n=17): revealed greater abduction, joint narrowing and included primarily patients with lateral KOA. The anterior draw group (n=10): revealed greater anterior draw, external tibial rotation, lateral tibial shift, adduction, and joint narrowing. This group was composed of patients with medial KOA, some degree of anterior cruciate ligament lesion and the greatest KOA score. The external rotation group (n=19): revealed greater external tibial rotation, lateral tibial shift, adduction, and joint narrowing while no anterior draw was observed. This group included primarily patients with medial collateral and posterior cruciate ligament lesions.

Patients with KOA can, based on their gait patterns, be classified into four subgroups, which relate to their clinical characteristics. The findings add to our understanding of associations between disease pathology characteristics in the knee and the pathomechanics in patients with KOA. A next step is to investigate if patients in the pathomechanic clusters have different outcomes following total knee arthroplasty.

This study compared the pullout forces of the initial implantation and the “cement-in-cement” revision technique for short and standard-length (125 mm vs. 150 mm) Exeter^® V40 femoral stems used in total hip arthroplasty (THA). The idea that the pullout force for a double taper slip stem is relative to the force applied to the femur and that “cement-in-cement” revision provides the same reproduction of force.

A total sample size of 15 femoral stems were tested (Short, n = 6 and Standard, n = 9). 3D printed fixtures for repeatable sample preparation were used to minimize variance during testing. To promote stem subsidence and to simulate an in vivo environment, the samples were placed in an incubator at 37°C at 100% humidity and experienced a constant compressive loading of 1335 N for 14 days. The samples underwent a displacement-controlled pullout test. After the initial pullout test, “cement-in-cement” revision will be performed and tested similar to the initial implantation to observe the efficacy of the revision technique. To compare the pullout forces between the two groups, a Kruskal-Wallis test using a significance level of 0.05 was conducted.

The mean maximum pullout force for the short and standard-length femoral stems were 3939 ± 1178 N and 5078 ± 1168 N, respectively. The Kruskal-Wallis test determined no statistically significant difference between the two groups for the initial implantation (p = 0.13). The “cement-in-cement” revision pullout force will be conducted in future testing.

This study demonstrated the potential use of short stem designs for THA as it provides similar levels of fixation as the standard-length femoral stem. The potential benefits for using a short stem design would be providing similar load transfer to the proximal femur, preserving proximal metaphyseal femoral bone in primary replacement, and reducing the invasiveness during revision.

Osteoclasts (OCs) are multinucleated cells that play a pivotal role in skeletal development and bone remodeling. Abnormal activation of OCs contributes to the development of bone-related diseases, such as osteoporosis, bone metastasis and osteoarthritis. Restoring the normal function of OCs is crucial for bone homeostasis. Recently, RNA therapeutics emerged as a new field of research for osteoarticular diseases.

The aim of this study is to use non-coding RNAs (ncRNAs) to molecularly engineer OCs and modulate their function. Specifically, we investigated the role of the microRNAs (namely miR-16) and long ncRNAs (namely DLEU1) in OCs differentiation and fusion.

DLEU1/DLEU2 region, located at chromosome 13q14, also encodes miR-15 and miR-16. Our results show that levels of these ncRNA transcripts are differently expressed at distinct stages of the OCs differentiation. Specifically, silencing of DLEU1 by small interfering RNAs (siDLEU1) and overexpression of miR-16 by synthetic miRNA mimics (miR-16-mimics) led to a significant reduction in the number of OCs formed per field (OC/field), both at day 5 and 9 of the differentiation stage. Importantly, time-lapse analysis, used to track OCs behavior, revealed a significant decrease in fusion events after transfection with siDLEU1 or miR-16-mimics and an alteration in the fusion mode and partners. Next, we investigated the migration profile of these OCs, and the results show that only miR-16-mimics-OCs, but not siDLEU-OCs, have a lower percentage of immobile cells and an increase in cells with mobile regime, compared with controls. No differences in cell shape were found. Moreover, mass-spectrometry quantitative proteomic analysis revealed independent effects of siDLEU1 and miR-16-mimics at the protein levels. Importantly, DLEU1 and miR-16 act by distinct processes and pathways.

Collectively, our findings support the ncRNAs DLEU1 and miR-16 as therapeutic targets to modulate early stages of OCs differentiation and, consequently, to impair OC fusion, advancing ncRNA-therapeutics for bone-related diseases.

Acknowledgements: Authors would like to thank to AO CMF / AO Foundation (AOCMFS-21-23A). SRM and MIA are supported by FCT (SFRH/BD/147229/2019 and BiotechHealth Program; CEECINST/00091/2018/CP1500/CT0011, respectively).

Meniscal injuries affect over 1.5 million people across Europe and the USA annually. Injury greatly reduces knee joint mobility and quality of life and frequently leads to the development of osteoarthritis. Tissue engineered strategies have emerged in response to a lack of viable treatments for meniscal pathologies. However, to date, constructs mimicking the structural and functional organisation of native tissue, whilst promoting deposition of new extracellular matrix, remains a bottleneck in meniscal repair. 3D bioprinting allows for deposition and patterning of biological materials with high spatial resolution. This project aims to develop a biomimetic 3D bioprinted meniscal substitute.

Meniscal tissue was characterised to effectively inform the design of biomaterials for bioprinting constructs with appropriate structural and functional properties. Histology, gene expression and mass spectrometry were performed on native tissue to investigate tissue architecture, matrix components, cell populations and protein expression regionally across the meniscus. 3D laser scanning and magnetic resonance imaging were employed to acquire the external geometrical information prior to fabrication of a 3D printed meniscus. Bioink suitability was investigated through regional meniscal cell encapsulation in blended hydrogels, with the incorporation of growth factors and assessed for their suitability through rheology, scanning electron microscopy, histology and gene expression analysis.

Meniscal tissue characterisation revealed regional variations in matrix compositions, cellular populations and protein expression. The process of imaging through to 3D printing highlighted the capability of producing a construct that accurately replicated meniscal geometries. Regional meniscal cell encapsulation into hydrogels revealed a recovery in cell phenotype, with the incorporation of growth factors into the bioink's stimulating cellular re-differentiation and improved zonal functionality.

Meniscus biofabrication highlights the potential to print patient specific, customisable meniscal implants. Achieving zonally distinct variations in cell and matrix deposition highlights the ability to fabricate a highly complex tissue engineered construct.

Acknowledgements: This work was undertaken as part of the UK Research and Innovation (UKRI)-funded CDT in Advanced Biomedical Materials.

Radioprotective gowns are an essential part of operating in orthopaedicse. As we are aware from the evidence, surgeons, and in particular orthopaedic surgeons, are at risk of developing chronic neck and back pain. This is likely a result of the combination of of long operations, heavy equipment, radioprotective gowns and poor ergonomic set up.

Women are a minority in orthopaedics. Amongst trainees there has been an improvement with 20–25% of current trainees are women, however at consultant level this percentage is a lot lower at 5–7%.

Radioprotective gowns worn by trainees are frequently not well fitted and few surgeons have access to bespoke fitted gowns. A questionnaire given to 32 trainees in the region found a significant burden of back pain in trainees and 57% of surgeons felt their gowns were not appropriately fitted. In this study every woman questioned reported back pain as a result of operating and 87% felt the gowns used exacerbated back pain, this figure was 56% in men.

80% of surgeons felt that surgeons would benefit from bespoke fitted gowns, even those that did not themselves have severe back pain. 45% of trainees felt their pain was moderate to severe. In surgery we have the responsibility to protect ourselves and our colleagues from work based injury and illness. Back pain should not be ignored as a symptom and radioprotective gowns is a good place to start.

Overall the majority the gowns exacerbated their back pain during or after procedures, worse in women as described above. We can use this data and do what we can to provide trainees with a range of sizes whilst working in hospitals during their training. Anectodally women sizes were less available in the departments and we can work to improve this and reduce the burden of pain amongst surgeons.

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:

There has been extensive research into neck of femur fractures in the elderly. Fragility non-hip femoral fractures share many of the same challenges [1]. Surgical management is complex, patients are frail and mortality rates have been reported as high as 38% [2]. Despite this, relatively little data is available evaluating the level of MDT care provided to non-hip femoral fractures.

This audit aimed to evaluate the standard of MDT care provided for patients with non-hip femoral fractures according to the NHFD key performance indicators. The following fractures were included in the dataset: distal femoral, femoral shaft and peri-prosthetic femoral. Patients under 65 were excluded. Data was retrospectively collected using post-operative and medical documentation. Performance was assessed according to five key performance indicators:

38 patients met the inclusion criteria. 84% of patients were seen by orthogeriatrics within 72 hours of admission. 32% of patients were operated on within 36-hours of admission, with time to theatre exceeding 36-hours in 92% of peri-prosthetic fractures. 37% of patients were not advised to full weight bear post operatively. 84% of patients received a confusion assessment whilst 61% of patients were discharged to their prior place of living.

Our results suggest that non-hip femoral fractures do not receive the same standard of MDT care as neck of femur fractures. Greater prioritisation of resources should be given to this patient subset so that care is equivalent to hip-fracture patients. Time to surgery is a particular area for improvement, particularly in peri-prosthetic fractures, a trend that is mirrored nationally. Greater emphasis should be placed on encouraging full-weight bearing post-operatively to prevent post-surgical complications.

There are no efficient treatment options for osteoarthritis (OA) that delay further progression. Besides osteoinduction, there is growing evidence of also anti-inflammatory, angiogenetic and neuroprotective effects of biodegradable magnesium-based biomaterials. Their use for the treatment of cartilage lesions in contrast is not well-evaluated yet.

Mg-cylinders were analysed in an in vitro and in vivo OA model. In vitro, SCP-1 stem cell line was analysed under inflammatory conditions and Mg-impact. In vivo, small Mg- and WE43 alloy-cylinders (1mm × 0,5mm) were implanted into the subchondral bone of the knee joint of 24 NZW rabbits after establishment of OA. As control, another 12 rabbits received only drill-holes. µCT-scan were performed and assessed for changes in bone volume and density. After euthanasia, cartilage was evaluated macroscopically and histologically after Safranin-O-staining. Furthermore, staining with CD271 directed antibody was performed to assess neuro-reactivity.

In vitro, an increased gene expression of extracellular matrix proteins as collagen II or aggrecan even under inflammatory conditions was observed under Mg-impact. In vivo, µCT evaluation revealed twice-elevated values for bone volume in femoral condyles with Mg-cylinders compared to controls while density remained unchanged. Cartilage showed no significant differences between the groups. Mg- and WE-samples showed significantly lower levels of CD271+ cells in the cartilage and bone of the operated joints than in non-operated joints, which was not the case in the Drilling-group. Furthermore, bone in operated knees of Drilling-group showed a strong trend to an increase in CD271+ cells compared to both Cylinder-groups. Counting of CD271+ vessels revealed that this difference was attributable to a higher amount of these vessels.

The in vitro results indicate a potential cartilage regenerative activity of the degradable Mg-based material. While so far there was no positive effect on the cartilage itself in vivo, implantation of Mg-cylinders seemed to reduce pain-mediating vessels.

Acknowledgements: This work is funded by the German Research Foundation (DFG, project number 404534760). We thank Björn Wiese for production of the cylinders.

Surgical education of fracture fixation biomechanics relies mainly on simplified illustrations to distill the essence of the underlying principles. These mostly consist of textbook drawings or hands-on exercises during courses, both with unique advantages such as broad availability and haptics, respectively. Computer simulations are suited to bridge these two approaches; however, the validity of such simulations must be guaranteed to teach the correct aspects. Therefore, the aim of this study was to validate finite element (FE) simulations of bone-plate constructs to be used in surgical education in terms of fracture gap movement and implant surface strain.

The validation procedure was conducted in a systematic and hierarchical manner with increasing complexity. First, the material properties of the isolated implant components were determined via four-point bending of the plate and three-point bending of the screw. Second, stiffness of the screw-plate interface was evaluated by means of cantilever bending to determine the properties of the locking mechanism. Third, implant surface strain and fracture gap motion were measured by testing various configurations of entire fixation constructs on artificial bone (Canevasit) in axial compression. The determined properties of the materials and interfaces assessed in these experiments were then implemented into FE models of entire fixation constructs with different fracture width and screw configurations. The FE-predicted implant surface strains and fracture gap motions were compared with the experimental results.

The simulated results of the different construct configurations correlated strongly with the experimentally measured fracture gap motions (R²>0.99) and plate surface strains (R²>0.95).

In a systematic approach, FE model validation was achieved successfully in terms of fracture gap motion and implant deformation, confirming trustworthiness for surgical education. These validated models are used in a novel online education tool OSapp (https://osapp.ch/) to illustrate and explain the biomechanical principles of fracture fixations in an interactive manner.

In chronically infected fracture non-unions, treatment requires extensive debridement to remove necrotic and infected bone, often resulting in large defects requiring elaborate and prolonged bone reconstruction. One approach includes the induced membrane technique (IMT), although the differences in outcome between infected and non-infectious aetiologies remain unclear. Here we present a new rabbit humerus model for IMT secondary to infection, and, furthermore, we compare bone healing in rabbits with a chronically infected non-union compared to non-infected equivalents.

A 5 mm defect was created in the humerus and filled with a polymethylmethacrylate (PMMA) spacer or left empty (n=6 per group). After 3 weeks, the PMMA spacer was replaced with a beta-tricalcium phosphate (chronOs, Synthes) scaffold, which was placed within the induced membrane and observed for a further 10 weeks. The same protocol was followed for the infected group, except that four week prior to treatment, the wound was inoculated with Staphylococcus aureus (4×10⁶ CFU/animal) and the PMMA spacer was loaded with gentamicin, and systemic therapy was applied for 4 weeks prior to chronOs application.

All the animals from the infected group were culture positive during the first revision surgery (mean 3×10⁵ CFU/animal, n= 12), while at the second revision, after antibiotic therapy, all the animals were culture negative. The differences in bone healing between the non-infected and infected groups were evaluated by radiography and histology. The initially infected animals showed impaired bone healing at euthanasia, and some remnants of bacteria in histology. The non-infected animals reached bone bridging in both empty and chronOs conditions.

We developed a preclinical in vivo model to investigate how bacterial infection influence bone healing in large defects with the future aim to explore new treatment concepts of infected non-union.

Tendons and tendon-to-bone entheses don't usually regenerate after injury, and the hierarchical organization of such tissues makes them challenging sites of study for tissue engineers. In this study, we have tried a novel approach using miRNA and a bioactive bioink to stimulate the regeneration of the enthesis. microRNAs (miRNAs) are short, non-coding sequences of RNA that act as post-transcriptional regulators of gene and protein expression [1]. Mimics or inhibitors of specific miRNAs can be used to restore lost functions at the cell level or improve healing at the tissue level [2,3]. We characterized the healing of a rat patellar enthesis and found that miRNA-16-5p was upregulated in the fibrotic portion of the injured tissue 10 days after the injury. Based on the reported interactions of miRNA-16-5p with the TGF-β pathway via targeting of SMAD3, we aimed to explore the effects of miRNA-16-5p mimics on the tenogenic differentiation of adipose-derived stem cells (ASCs) encapsulated in a bioactive bioink [4,5]. Bioinks with different properties are used for the 3D printing of biomimetic constructs. By integrating cells, materials, and bioactive molecules it is possible to tailor the regenerative capacity of the ink to meet the particular requirements of the tissue to engineer [5]. Here we have encapsulated ASCs in a gelatin-methacryloyl (GelMa) bioink that incorporates miR-16-5p mimics and magnetically responsive microfibers (MRFs). When the bioink is crosslinked in the presence of a magnetic field, the MRFs align unidirectionally to create an anisotropic construct with the ability to promote the tenogenic differentiation of the encapsulated ASCs. Additionally, the obtained GelMA hydrogels retained the encapsulated miRNA probes, which permitted the effective 3D transfection of the ASC and therefore, the regulation of gene expression, allowing to investigate the effects of the miR-16-5p mimics on the tenogenic differentiation of the ASCs in a biomimetic scenario.

The objective of this study was to use patient-specific finite element modeling to measure the 3D interfragmentary strain environment in clinically realistic fractures. The hypothesis was that in the early post-operative period, the tissues in and around the fracture gap can tolerate a state of strain in excess of 10%, the classical limit proposed in the Perren strain theory.

Eight patients (6 males, 2 females; ages 22–95 years) with distal femur fractures (OTA/AO 33-A/B/C) treated in a Level I trauma center were retrospectively identified. All were treated with lateral bridge plating. Preoperative computed tomography scans and post-operative X-rays were used to create the reduced fracture models. Patient-specific materials properties and loading conditions (20%, 60%, and 100% body weight (BW)) were applied following our published method.[1]

Elements with von Mises strains >10% are shown in the 100% BW loading condition. For all three loading scenarios, as the bridge span increased, so did the maximum von Mises strain within the strain visualization region. The average gap closing (Perren) strain (mean ± SD) for all patient-specific models at each body weight (20%, 60%, and 100%) was 8.6% ± 3.9%, 25.8% ± 33.9%, and 39.3% ± 33.9%, while the corresponding max von Mises strains were 42.0% ± 29%, 110.7% ± 32.7%, and 168.4% ± 31.9%. Strains in and around the fracture gap stayed in the 2–10% range only for the lowest load application level (20% BW).

Moderate loading of 60% BW and above caused gap strains that far exceeded the upper limit of the classical strain rule (<10% strain for bone healing). Since all of the included patients achieved successful unions, these findings suggest that healing of distal femur fractures may be robust to localized strains greater than 10%.

Several emerging reports suggest an important involvement of the hindfoot alignment in the outcome of knee osteotomy. At present, studies lack a comprehensive overview. Therefore, we aimed to systematically review all biomechanical and clinical studies investigating the role of the hindfoot alignment in the setting of osteotomies around the knee.

A systematic literature search was conducted on multiple databases combining “knee osteotomy” and “hindfoot/ankle alignment” search terms. Articles were screened and included according to the PRISMA guidelines. A quality assessment was conducted using the Quality Appraisal for Cadaveric Studies (QUACS) - and modified methodologic index for non-randomized studies (MINORS) scales.

Three cadaveric, fourteen retrospective cohort and two case-control studies were eligible for review. Biomechanical hindfoot characteristics were positively affected (n=4), except in rigid subtalar joint (n=1) or talar tilt (n=1) deformity. Patient symptoms and/or radiographic alignment at the level of the hindfoot did also improve after knee osteotomy (n=13), except in case of a small pre-operative lateral distal tibia- and hip knee ankle (HKA) angulation or in case of a large HKA correction (>14.5°). Additionally, a pre-existent hindfoot deformity (>15.9°) was associated with undercorrection of lower limb alignment following knee osteotomy. The mean QUACS score was 61.3% (range: 46–69%) and mean MINORS score was 9.2 out of 16 (range 6–12) for non-comparative and 16.5 out of 24 (range 15–18) for comparative studies.

Osteotomies performed to correct knee deformity have also an impact on biomechanical and clinical outcomes of the hindfoot. In general, these are reported to be beneficial, but several parameters were identified that are associated with newly onset – or deterioration of hindfoot symptoms following knee osteotomy. Further prospective studies are warranted to assess how diagnostic and therapeutic algorithms based on the identified criteria could be implemented to optimize the overall outcome of knee osteotomy.

Remark: Aline Van Oevelen and Arne Burssens contributed equally to this work

Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue.

Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors.

Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria.

Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and sex hormonal differences were correlated with tendon-injured patients. It was established the optimal amount of MPC/MSC human cell (collected from different patients during femoral neck osteotomy). Finally, most suitable biomaterials for tendon regeneration and polymer tendon-like structure were identified. Hyaluronic acid, chemical surface and soft-molecular imprinting (SOFT-MI) was used to functionalize the scaffold.

These preliminary results are promising. It will be necessary to enroll many more patients to identify genetic status connected with the onset of tendinopathy. The functional and structural characterization of smart bioactive tendon in dynamic environment will represent the next project step.

No proven long-term joint-preserving treatment options exist for patients with irreparable meniscal damage. This study aimed to assess gait kinematics and contact pressures of novel fibre-matrix reinforced polyvinyl alcohol-polyethylene glycol (PVA-PEG) hydrogel meniscus implanted ovine stifle joints against intact stifles in a gait simulator.

The gait simulator controlled femoral flexion-extension and applied a 980N axial contact force to the distal end of the tibia, whose movement was guided by the joint natural ligaments (Bartolo; ORS 2021;p1657- LB). Five right stifle joints from sheep aged >2 years were implanted with a PVA-PEG total medial meniscus replacement, fixed to the tibia via transosseous tunnels and interference screws. Implanted stifle joint contact pressures and kinematics in the simulator were recorded and compared to the intact group. Contact pressures on the medial and lateral condyles were measured at 55° flexion using Fujifilm Prescale Low Pressure film inserted under the menisci. 3D kinematics were measured across two 30 second captures using the Optotrak Certus motion-tracking system (Northern Digital Inc.).

Medial peak pressures were not significantly different between the implanted and intact groups (p>0.4), while lateral peak pressures were significantly higher in the implanted group (p<0.01). Implanted stifle joint kinematics in the simulator did not differ significantly from the intact baseline (p>0.01), except for in distraction-compression (p<0.01).

Our findings show that the fibre-matrix reinforced PVA-PEG hydrogel meniscal replacement restored the medial peak contact pressures. Similar to published literature (Fischenich; ABE 2018;46(11):1–12), the lateral peak pressures in the implanted group were higher than the intact. Joint kinematics were similar across groups, with slightly increased internal-external rotation in the implanted group. These findings highlight the effectiveness of the proposed approach and motivate future work on the development of a total meniscal replacement.

Low back pain (LBP) is the main cause of disability worldwide and is primarily triggered by intervertebral disc degeneration (IDD). Although several treatment options exist, no therapeutic tool has demonstrated to halt the progressive course of IDD. Therefore, several clinical trials are being conducted to investigate different strategies to regenerate the intervertebral disc, with numerous studies not reaching completion nor being published. The aim of this study was to analyze the publication status of clinical trials on novel regenerative treatments for IDD by funding source and identify critical obstacles preventing their conclusion.

Prospective clinical trials investigating regenerative treatments for IDD and registered on ClinicalTrials.gov were included. Primary outcomes were publication status and investigational treatment funding. Fisher's exact test was utilized to test the association for categorical variables between groups.

25 clinical trials were identified. Among these, only 6 (24%) have been published. The most common source of funding was university (52%), followed by industry (36%) and private companies (12%). Investigational treatments included autologous (56%) or allogeneic (12%) products alone or in combination with a carrier or delivery system (32%). The latter were more likely utilized in industry or privately funded studies (Fig. 1, p=0.0112). No significant difference was found in terms of funding regarding the publication status of included trials (Table 1, p=0.9104).

Most clinical trials investigating regenerative approaches for the treatment of IDD were never completed nor published. This is likely due to multiple factors, including difficult enrollment, high dropout rate, and publication bias³. More accurate design and technical support from stakeholders and clinical research organization (CROs) may likely increase the quality of future clinical trials in the field.

For any figures or tables, please contact the authors directly.

As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. The aim of this research was to create bioinks that can be injected or 3D bioprinted to aid osteochondral defect repair using human cells.

Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA). Chondrocytes or mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also produced via 3D culture and then bioprinted to accelerate cell growth and development of ECM in bioprinted constructs.

Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture over 28 days, with accelerated cell growth seen with inclusion of MSC or chondrocyte spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects (OCDs) and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion we developed novel composite AlgMA/GelMA bioinks that can be triple-crosslinked, facilitating dense chondrocyte and MSC growth in constructs following 3D bioprinting. The bioink can be injected or 3D bioprinted to successfully repair in vitro OCDs, offering hope for a new approach to treating AC defects.

Cartilage lacks the ability to self-repair when damaged, which can lead to the development of degenerative joint disease. Despite intensive research in the field of cartilage tissue engineering, there is still no regenerative treatment that consistently promotes the development of hyaline cartilage. Extracellular matrix (ECM) derived hydrogels have shown to support cell adhesion, growth and differentiation [1,2]. In this study, porcine articular cartilage was decellularized, solubilised and subsequently modified into a photo-crosslinkable methacrylated cartilage ECM hydrogel. Bone marrow derived mesenchymal stem/stromal cells (MSCs) were encapsulated into both methacrylated ECM hydrogels (ECM-MA) and gelatin methacryloyl (GelMA) as control hydrogel, and their chondrogenic potential was assessed using biochemical assays and histological analysis. We found that successful decellularization of the cartilage tissue could be achieved while preserving key ECM components, including collagen and glycosaminoglycans. A live-dead assay demonstrated good viability of MSCs withing both GelMA and ECM-MA hydrogels on day 7. Large increases in sGAG accumulation was observed after 21 days of culture in chondrogenic media in both groups. Histological analysis revealed the presence of a more fibrocartilage tissue in the GelMA group, while cells embedded within the ECM-MA showed a round and chondrocytic-like morphology. Both groups stained positively for proteoglycans and collagen, with limited evidence of calcium deposition following Alizarin Red staining. These results show that ECM-MA hydrogels support a hyaline cartilage phenotype and robust cartilaginous matrix production. Future studies will focus on the printability of ECM-MA hydrogels to enable their use as bioinks for the biofabrication of functional tissues.

Radial head fractures are among the most common fractures around the elbow. Radial head arthroplasty is one of the surgical treatment options after complex radial head fractures. This surgery is usually done under general anaesthesia. However, there is a recent anaesthetic technique - wide awake local anaesthesia no tourniquet (WALANT) - that has proven useful in different surgical settings, such as in distal radius or olecranon fractures. It allows a good haemostatic control without the use of a tourniquet and allows the patient to actively collaborate during the surgical procedure. Furthermore, there are no side effects or complications caused by the general anaesthesia and there's an earlier patient discharge.

The authors present the case of a seventy-six-year-old woman who presented to the emergency department after a fall from standing height with direct trauma to the left elbow. The radiological examination revealed a complete intra-articular comminuted fracture of the radial head (Mason III).

Clinical management: The patient was submitted to surgery with radial head arthroplasty, using WALANT. The surgery was successfully completed without pain. There were no intra or immediate post-operative complications and the patient was discharged on the same day. Six weeks after surgery, the patient had almost full range of motion and was very pleased with the functional outcome, with no limitations on her activities of daily living.

The use of WALANT has been expanded beyond the hand and wrist surgery. It is a safe and simple option for patients at high risk of general anaesthesia, allowing similar surgical outcomes without the intraoperative and postoperative complications of general anaesthesia and permitting an earlier hospital discharge. Furthermore, it allows the patient to actively collaborate during the surgery, providing the surgeons the opportunity to evaluate active mobility and stability, permitting final corrections before closing the incision.

Renal Osteodystrophy is a type of metabolic bone disease characterized by bone mineralization deficiency due to electrolyte and endocrine abnormalities. Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. Treatment involves medical management to resolve the etiology of the underlying renal condition, as well as management (and prevention) of pathological fractures.

A 66-year-old female patient, with severe osteoporosis and chronic kidney disease undergoing haemodialysis, has presented with multiple fractures along the years. She was submitted to bilateral proximal femoral nailing as fracture treatment on the left and prophylactically due to pathological bone injury on the right, followed by revision of the left nail with a longer one after varus angulation and fracture distal to the nail extremity. Meanwhile, the patient suffered a pathological fracture of the radial and cubital diaphysis and was submitted to conservative treatment with cast, with consolidation of the fracture. Posteriorly, she re-fractured these bones after a fall and repeated the conservative treatment.

Clinical management: There is a multidisciplinary approach to manage the chronic illness of the patient, including medical management to resolve the etiology and consequences of her chronic kidney disease, pain control, conservative or surgical fracture management and prevention of falls.

The incidence of chronic renal disease is increasing and the patients with this condition live longer than previously and are more physically active. Thus, patients may experience trauma as a direct result of increased physical activity in a setting of weakened pathologic bone. Their quality of life is primarily limited by musculoskeletal problems, such as bone pain, muscle weakness, growth retardation, and skeletal deformity. A multidisciplinary approach is required to treat these patients, controlling their chronic diseases, managing fractures and preventing falls.

Periosteal mesenchymal stem cells (PMSC) are an emerging niche of stem cells to enhance bone healing by tissue engineering process. They have to be differentiated into osteoprogenitors in order to synthesize new bone matrix. In vitro differentiation with specific differentiation medium (DM) is not exactly representative of what occurs in vivo. The interaction between PMSC and growth factors (GF) present in biological matrix is somewhat less understood. The goal of this study is to explore the possibility of spontaneous PMSC differentiation in contact with different biological matrices without DM.

500.000 porcine PMSC were seeded on 6-well plates and cultured with proliferation medium (PM). When reaching 80% confluence, biological samples (n=3) of demineralized bone matrix (DBM), decellularized porcine bone allograft (AOp), human bone allograft (AOh), human periosteum (HP) and human fascia lata (HFL) were added. Negative and positive control wells included cells with only PM or DM, respectively. The differentiation progress was assessed by Alizarin Red staining at days 7, 14 and 21. Bone morphogenetic protein content (BMP 2, 4, 5, 6, 7, 8, 9 and 11) of each sample was also investigated by western blot.

Alizarin red highlighted bone nodules neoformation on wells containing AOp, AOh and DBM, like positive controls. HP and HFL wells did not show any nodules. These results are correlated to a global higher BMP expression profile in AOp than in HP and HFL but not statistically significant (p=0.38 and p>.99, respectively). The highest expression in each tissue was that of BMP2 and BMP7, which play an important role in osteoinduction.

PMSC are well known to participate to bone formation but, despite BMP presence in HP and HFL, they did not permit to achieve osteogenesis alone. The bone contact seems to be essential to induce in vitro differentiation into osteoprogenitors.

There remains much debate regarding the optimal method for surgical management of patients with long head of biceps pathology. The aim of this study was to compare the outcomes of tenotomy versus tenodesis.

This systematic review and meta-analysis was registered on PROSPERO (ref: CRD42020198658). Electronic databases searched included EMBASE, Medline, PsycINFO, and Cochrane Library. Randomized controlled trials (RCTs) comparing tenotomy versus tenodesis were included. Risk of bias within studies was assessed using the Cochrane risk of bias v2.0 tool and the Jadad score. The primary outcome included patient reported functional outcome measures pooled using standardized mean difference (SMD) and a random effects model. Secondary outcome measures included pain (visual analogue scale VAS), rate of Popeye deformity, and operative time.

860 patients from 11 RCTs (426 tenotomy vs 434 tenodesis) were included in the meta-analysis. Pooled analysis of all PROMs data demonstrated comparable outcomes between tenotomy vs tenodesis (SMD 0.14, 95% CI −0.04 to 0.32; p=0.13). Sensitivity analysis comparing RCTs involving patients with and without an intact rotator cuff did not change the primary outcome. There was no significant difference for pain (VAS). Tenodesis resulted in a lower rate of Popeye deformity (OR 0.29, 95% CI 0.19 to 0.45, p < 0.00001). Tenotomy demonstrated a shorter operative time (MD 15.21, 95% CI 1.06 to 29.36, p < 0.00001).

Aside from a lower rate of cosmetic deformity, tenodesis yielded no measurable significant benefit to tenotomy for addressing pathology in the long head of biceps. A large multi-centre clinical effectiveness randomised controlled trial is needed to provide clarity in this area.

The study compared thigh-shank and shank-foot coordination during gait before and after total knee arthroplasty (TKA) with controls (CTRL).

Twenty-seven patients (male=15/female=12; age=63.2±6.9 years) were evaluated one month prior to and twelve months after surgery, and compared to 27 controls (male=14/female=13; age=62.2±4.3). The participants were outfitted with a full-body marker set. Gait speed (normalized by leg length) was calculated. The time series of the thigh, shank, and foot orientation in relation to the laboratory coordinate system were extracted. The coordination between the thigh-shank and shank-foot in the sagittal plane were calculated using a vector coding technique. The coupling angles were categorized into four coordination patterns. The stance phase was divided into thirds: early, mid, and late stance. The frequency of each pattern and gait speed were compared using a one-way ANOVA with a post-hoc Bonferroni correction.

Walking speed and shank-foot coordination showed no differences between the groups. The thigh-shank showed differences. The pre-TKA group showed a more in-phase pattern compared to the CTRL group during early-stance. During mid-stance, the pre- and post-TKA presented a more in-phase pattern compared to the CTRL group. Regarding shank-foot coordination, the groups presented an in-phase and shank pattern, with more shank phase during mid-stance and more in-phase during late-stance.

The pre-TKA group showed greater differences than the post-TKA compared to the controls. The more in-phase pattern in the pre- and post-TKA groups could relate to a reduced capacity for the thigh that leads the movement. During mid-stance in normal gait, the knee is extending, where the thigh and shank movements are in opposite directions. The in-phase results in the TKA groups indicate knee stiffness during the stance phase, which may relate to a muscular deficit or a gait strategy to reduce joint stress.

MicroRNA (miR) delivery to regulate chronic inflammation hold extraordinary promise, with new therapeutic possibilities emanating from their ability to fine-tune multiple target gene regulation pathways which is an important factor in controlling aberrant inflammatory reactions in complex multifactorial disease. However, several hurdles have prevented advancements in miR-based therapies. These include off-target effects of miRs, limited trafficking, and inefficient delivery. We propose a magnetically guided nanocarrier to transport therapeutically relevant miRs to assist self- resolving inflammation processes at injury sites and reduce the impact of chronic inflammation- related diseases such as tendinopathies. The high prevalence, significant socio-economic burden and increasing recognition of dysregulated immune mediated pathways in tendon disease provide a compelling rationale for exploring inflammation-targeting strategies as novel treatments in this condition. By combining cationic polymers, miR species (e.g., miR 29a, miR155 antagonist), and magnetic nanoparticles in the form of magnetoplexes with highly efficient magnetofection procedures, we developed inexpensive, easy-to-fabricate, and biocompatible systems with competent miR-binding and fast cellular uptake into different types of human cells, namely macrophages and tendon-derived cells. The system was shown to be cell-compatible and to successfully modulate the expression and production of inflammatory markers in tendon cells, with evidence of functional pro-healing changes in immune cell phenotypes. Hence, magnetoplexes represent a simple, safe, and non-viral nanoplatform that enables contactless miR delivery and high- precision control to reprogram cell profiles toward improved pro-regenerative environments.

Acknowledgements: ERC CoG MagTendon No.772817; FCT Doctoral Grant SFRD/BD/144816/2019, and TERM

RES Hub (Norte-01-0145-FEDER-022190).

To analyse the efficacy and safety of cellular therapy utilizing Mesenchymal Stromal Cells (MSCs) in the management of rotator cuff(RC) tears from clinical studies available in the literature.

We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library on August 2021 for studies analyzing the efficacy and safety of cellular therapy (CT) utilizing MSCs in the management of RC tears. VAS for pain, ASES Score, DASH Score, Constant Score, radiological assessment of healing and complications and adverse events were the outcomes analyzed. Analysis was performed in R-platform using OpenMeta [Analyst] software.

Smartphones are often equipped with inertial sensors capable of measuring individuals' physical activities. Their role in monitoring the patients' physical activities in telemedicine, however, needs to be explored. The main objective of this study was to explore the correlation between a participant's daily step counts and the daily step counts reported by their smartphone. This prospective observational study was conducted on patients undergoing lower limb orthopedic surgery and a group of non-patients. The data collection period was from 2 weeks before until four weeks after the surgery for the patients and two weeks for the non-patients. The participants' daily steps were recorded by physical activity trackers employed 24/7, and an application recorded the number of daily steps registered by the participants' smartphones. We compared the cross-correlation between the daily steps time-series taken from the smartphones and physical activity trackers in different groups of participants. We also employed mixed modeling to estimate the total number of steps. Overall, 1067 days of data were collected from 21 patients (11 females) and 10 non-patients (6 females). The cross-correlation coefficient between the smartphone and physical activity tracker was 0.70 [0.53–0.83]. The correlation in the non-patients was slightly higher than in the patients (0.74 [0.60–0.90] and 0.69 [0.52–0.81], respectively). Considering the ubiquity, convenience, and practicality of smartphones, the high correlation between the smartphones and the total daily step time-series highlights the potential usefulness of smartphones in detecting the change in the step counts in remote monitoring of the patient's physical activity.

The effect of high-fat diet and testosterone replacement therapy upon bone remodelling was investigated in orchiectomised male APOE-/- mice.

Mice were split in to three groups: sham surgery + placebo treatment (control, n=9), orchiectomy plus placebo treatment (n=8) and orchiectomy plus testosterone treatment (n=10). Treatments were administered via intramuscular injection once a fortnight for 17 weeks before sacrifice at 25 weeks of age. Tibiae were scanned ex-vivo using µCT followed by post-analysis histology and immunohistochemistry.

Previously presented µCT data demonstrated orchiectomised, placebo treated mice exhibited significantly reduced trabecular bone volume, number, thickness and BMD compared to control mice despite no significant differences in body weight. Trabecular parameters were rescued back to control levels in orchiectomised mice treated with testosterone. No significant differences were observed in the cortical bone.

Assessment of TRAP stained FFPE sections revealed no significant differences in osteoclast or osteoblast number along the endocortical surface. IHC assessment of osteoprotegerin (OPG) expression in osteoblasts is to be quantified alongside markers of osteoclastogenesis including RANK and RANKL.

Results support morphological analysis of cortical bone where no change in cortical bone volume or density between groups is in line with no significant change in osteoblast or osteoclast number and percentage across all three groups.

Future work will include further IHC assessment of bone remodelling and adiposity, as well as utilisation of mechanical testing to establish the effects of observed morphological differences in bone upon mechanical properties. Additionally, the effects of hormone treatments upon murine-derived bone cells will be investigated to provide mechanistic insights.

The aim of this study was to investigate the effect of different loading scenarios and foot positions on the configuration of the distal tibiofibular joint (DTFJ).

Fourteen paired human cadaveric lower legs were mounted in a loading frame. Computed tomography scans were obtained in unloaded state (75 N) and single-leg loaded stand (700 N) of each specimen in five foot positions: neutral, 15° external rotation, 15° internal rotation, 20° dorsiflexion, and 20° plantarflexion. An automated three-dimensional measurement protocol was used to assess clear space (diastasis), translational angle (rotation), and vertical offset (fibular shortening) in each foot position and loading condition.

Foot positions had a significant effect on the configuration of DTFJ. Largest effects were related to clear space increase by 0.46 mm (SD 0.21 mm) in loaded dorsal flexion and translation angle of 2.36° (SD 1.03°) in loaded external rotation, both versus loaded neutral position. Loading had no effect on clear space and vertical offset in any position. Translation angle was significantly influenced under loading by −0.81° (SD 0.69°) in internal rotation only.

Foot positioning noticeably influences the measurement when evaluating the configuration of DTFJ. The influence of the weightbearing seems to have no relevant effect on native ankles in neutral position.

Prosthetic joint infection (PJI) is a serious complication following joint replacement. Antiseptic solutions are often used for intraoperative wound irrigation particularly in cases of revision for PJI. Antiseptic irrigation is intended to eradicate residual bacteria which may be either free floating or in residual biofilm although there is no clear clinical efficacy for its use. Also, reviewing the scientific literature there is discordance in in vitro results where some studies questions antiseptic efficacy whilst others suggest that even at low concentration antiseptic agents are effective at eradicating bacterial biofilms.

The aim of this in vitro study was to establish the efficacy of undiluted antiseptic agents at eradication of a typical PJI forming biofilm and determine the importance of an antiseptic neutralisation step in this assessment.

Mature Staphylococcus epidermidis biofilms grown on TiAl6V4 discs were submerged in chlorohexidine (CHL) gluconate 4%, povidone-iodine (PI) 10% or phosphate-buffered saline (PBS) control solution. The discs were then rinsed, the biofilm bacteria suspended in solution using sonication and vortexing, and the viable count (CFU/ml) of the bacterial suspensions determined. The rinse/suspension solution was either (a) PBS or (b) Dey-Engley neutralization broth (NB).

When PBS was used to rinse/suspend the biofilm a highly significant, 7.5 and 4.1, mean log reduction in biofilm vitality was observed from the control, for CHL 4% and PI 10%, respectively. However, when NB was the rinse/suspension solution the apparent antiseptic biofilm eradication efficacy was replaced with a statistically significant but clinically irrelevant less the one log-reduction in biofilm vitality.

Clinical antiseptic agents are ineffective at eradicating S. epidermidis biofilm in an in vitro PJI model and absence of a neutralisation step gives the false impression of efficacy. Antiseptics alone are an ineffective treatment for biofilm related PJI and no substitute for meticulous debridement.

Several studies have evaluated the risk of peroneal nerve (PN) injuries in all-inside lateral meniscal repair using standard knee magnetic resonance imaging (MRI) with the 30 degrees flexed knee position which is different from the knee position during actual arthroscopic lateral meniscal repair. The point of concern is “Can the risk of PN injury using standard knee MRIs be accurately determined”.

To evaluate and compare the risk of PN injury in all-inside lateral meniscal repair in relation to both borders of the popliteus tendon (PT) using MRIs of the two knee positions in the same patients.

Using axial MRI studies with standard knee MRIs and figure-of-4 with joint fluid dilatation actual arthroscopic lateral meniscal repair position MRIs, direct lines were drawn simulating a straight all-inside meniscal repair device from the anteromedial and anterolateral portals to the medial and lateral borders of the PT. The distance from the tip of each line to the PN was measured. If a line touched or passed the PN, a potential risk of iatrogenic injury was noted and a new line was drawn from the same portal to the border of the PN. The danger area was measured from the first line to the new direct line along the joint capsule.

In 28 adult patients, the closest distances from each line to the PN in standard knee MRI images were significantly shorter than arthroscopic position MRI images (all p-values < 0.05). All danger areas assessed in the actual arthroscopic position MRIs were included within the danger areas as assessed by the standard knee MRIs.

We found that the standard knee MRIs can be used to determine the risk of peroneal nerve injury in arthroscopic lateral meniscal repair, although the risks are slightly overestimated.

With an aging population and increase in total knee arthroplasty, periprosthetic distal femur fractures (PDFFs) have increased. The differences between these fractures and native distal femur fractures (NDFF) have not been comprehensively investigated. The purpose of this study was to compare the demographic, fracture, and treatment details of PDFFs compared to NDFFs.

A retrospective study of patients ≥ 18 years old who underwent surgical treatment for either a NDFF or a PDFF from 2010 to 2020 at a level 1 trauma center was performed. Demographics, AO/OTA fracture classification, quality of reduction, fixation constructs, and unplanned revision reoperation were compared between PDFF patients and NDFF patients using t-test and Fisher's exact test. 209 patients were identified with 70 patients having a PDFF and 139 patients having a NDFF. Of note, 48% of NDFF had a concomitant fracture of the ipsilateral knee (14%) or tibial plateau (15%). The most common AO/OTA classification for PDFFs was 33A3.3 (71%). NDFFs had two main AO/OTA classifications of 33C2.2 (28%) or 33A3.2. (25%). When controlling for patient age, bone quality, fracture classification, and fixation, the PDFF group had increased revision reoperation rate compared to NDFF (P < 0.05).

PDFFs tend to occur in elderly patients with low bone quality, have complete metaphyseal comminution, and be isolated; whereas, NDFF tend to occur in younger patients, have less metaphyseal comminution, and be associated with other fractures. When controlling for variables, PDFF are at increased risk of unplanned revision reoperation. Surgeons should be aware of these increased risks in PDFFs and future research should focus on these unique fracture characteristics to improve outcomes.

Neck of femur fractures are a common trauma presentation and patients with a history of malignancy are sent for long leg femur views (LLF), to exclude a distal lesion which would alter the management plan (Intra-medullary nail/Long stem Hemiarthroplasty). The aim of this is to identify incidence of malignancy on LLF views, the length of time in between each xray (XR) and to identify demographics.

Data was retrospectively collected from 01/01/2021 to 31/01/2021 from a single centre. All patients admitted to the Queen Elizabeth University Hospital had their electronic records (Bluespier, PACS, Clinical Portal) accessed. These confirmed if patients had a past medical history of malignancy, if they had LLF view and the time differences between diagnostic pelvis XR and LLF XR.

A total of 784 patients were identified in the specified time period. Of these, 138 were identified with a malignancy and there were 85 LLF views completed. LLF views diagnosed 1 patient with known prostate cancer that had a new distal femoral metastasis (Incidence = 1.28 cases per 1000). This patient underwent further imaging (MRI Femur) and received a long stem hip hemiarthroplasty. The average length of wait between the images was 9 hours 27 minutes.

LLF views can alter management of patients with malignancy and are therefore useful to perform. There can be a long delay between each image. Therefore we recommend imaging tumour with common bony metastasis (Renal, Thyroid, Breast, Prostrate, Lung) and other remaining tumours with known secondary metastasis. Imaging primary low risk (eg basal cell carcinoma) can lead to long delays in a frail patient cohort and consideration should be given to rationalise appropriate use of resources.

Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery.

To investigate temporal changes in synovial lymphatic system (SLS) drainage function after Anterior cruciate ligament (ACL) injury, a non-invasive ACL rupture model was used to induce the PTOA phenotype without altering the SLS structure.

We have created a non-invasive ACL rupture model in the right knee (single overload impact) of 12- week-old C57bl/6 male mice to mimic the ACL rupture-induced PTOA development. 70 kDa-TxRedDextran were injected into the right knee of the mice at 0, 1, 2, and 4 wks post modeling (n=5/group), and the fluorescence signal distribution and intensity were measured by the IVIS system at 1 and 6 hrs post-injection. After 24 hrs, the drainage lymph nodes and whole knee joint were harvested and subjected to ex vivo IVIS imaging and immunofluorescence detection respectively.

Manual ACL rupture was induced by 12N overloaded force and validated by a front drawer test. Intraarticular clearance of TxRed-Dextran detected by the IVIS was significantly reduced at 1, and 2 wks at a level of 43% and 55% respectively but was not significantly different from baseline levels at 4 wks (89%). TxRed-Dextran signal in draining lymph nodes was significantly reduced at 1 week at the level of but not for 2 and 4 wks compared to baseline levels (week 1–29%, week 2–50%, week 4–94%). TxRed-Dextran particle was significantly enriched in the synovium at 1, 2 wks but was not significantly different from baseline levels at 4 wks rupture-post ACL rupture (Particle numbers: Sham Ctrl-34 ±14, week 1, 113 ± 17; week 2, 89 ± 13; week 4, 46 ± 18; mean ± SD).

We observed the drainage function of SLS significantly decreased at 1 and 2 wks after the ACL rupture, and was slowly restored at 4 wks post-injury in a non-invasive ACL rupture model. Early impairment of SLS drainage function may lead to accumulation of inflammatory factors and promote PTOA progression.

Non-linear methods in statistical shape analysis have become increasingly important in orthopedic research as they allow for more accurate and robust analysis of complex shape data such as articulated joints, bony defects and cartilage loss. These methods involve the use of non-linear transformations to describe shapes, rather than the traditional linear approaches, and have been shown to improve the precision and sensitivity of shape analysis in a variety of applications. In orthopedic research, non-linear methods have been used to study a range of topics, including the analysis of bone shape and structure in relation to osteoarthritis, the assessment of joint deformities and their impact on joint function, and the prediction of patient outcomes following surgical interventions. Overall, the use of non-linear methods in statistical shape analysis has the potential to advance our understanding of the relationship between shape and function in the musculoskeletal system and improve the diagnosis and treatment of orthopedic conditions.

Bone infections due to fractures or implants are a big medical problem. In experimental medicine, many experimental models have been created on different animal species to simulate the disease condition and to do experience treatments. The aim of this paper was to present an antibacterial efficacy of using a bone allograft developed according to the Marburg system of bone bank on a model of chronic osteomyelitis induced in rabbits.

In research was used 54 rabbits. Osteomyelitis was induced in rabbits by a human strain of St. aureus ATCC 43300, in the rabbit femur. There have been created 3 groups of animals. In 1^st group used antibiotic impregnated biodegradable material “PerOssal”. In 2^nd group used antibiotic impregnated whole bone allograft. In 3^rd group used antibiotic impregnated perforated bone allograft. Evaluation of installation and evolution of the disease was done by microbiological. A separate study of microbiological data is presented here.

This study showed, in the 1^st and 3^rd groups there is a persistent decrease in CFU by 14 knocks to 120.4 in the 1^st group and to 3.5 in the 3^rd group, and in the 2^nd group, on the contrary, there is an increase in CFU to 237.33. This shows the lack of effectiveness of using a whole bone allograft.

The results showed, after 7 days there was no statistically significant difference between the groups. After 14 days the perforated bone allograft impregnated with antibiotic was better than the biodegradable material “PerOssal”.