Functional performance of a bi-layered chitosan-nano-hydroxyapatite osteochondral scaffold: a pre-clinical in vitro tribological study.

Osteochondral grafts are used for repair of focal osteochondral lesions. Autologous grafts are the gold standard treatment; however, limited graft availability and donor site morbidity restrict use. Therefore, there is a clinical need for different graft sources/materials which replicate natural cartilage function. Chitosan has been proposed for this application. The aim of this study was to assess the biomechanics and biotribology of a bioresorbable chitosan/chitosan-nano-hydroxyapatite osteochondral construct (OCC), implanted in an in vitro porcine knee experimental simulation model. The OCC implanted in different surgical positions (flush, proud and inverted) was compared to predicate grafts in current clinical use and a positive control consisting of a stainless steel graft implanted proud of the cartilage surface. After 3 h (10 800 cycles) wear simulation under a walking gait, subsidence occurred in all OCC samples irrespective of surgical positioning, but with no apparent loss of material and low meniscus wear. Half the predicate grafts exhibited delamination and scratching of the cartilage surfaces. No graft subsidence occurred in the positive controls but wear and deformation of the meniscus were apparent. Implanting a new chitosan-based OCC either optimally (flush), inverted or proud of the cartilage surface resulted in minimal wear, damage and deformation of the meniscus.

Is there a difference in the analgesic response to intra-articular bupivacaine injection in people with knee osteoarthritis pain with or without central sensitisation? Protocol of a feasibility randomised controlled trial.

INTRODUCTION: Pain is the main symptom of osteoarthritis (OA) with approximately 50% of patients reporting moderate-to-severe pain. Total knee replacement (TKR) is the ultimate treatment option to alleviate pain in knee OA. Nevertheless, TKR does not provide complete relief for all as approximately 20% of patients experience chronic postoperative pain. Painful peripheral stimuli may alter the central nociceptive pathways leading to central sensitisation that can influence treatment response in patients with OA. Currently, there is no objective protocol for detecting whether a patient will respond to a given treatment. Therefore, there is a need for a better mechanistic understanding of individual factors affecting pain relief, consequently informing personalised treatment guidelines. The purpose of this research is to examine the feasibility of conducting a full-scale mechanistic clinical trial in painful knee OA investigating the analgesic response to intra-articular bupivacaine between those with or without evidence of central sensitisation. METHODS AND ANALYSIS: The Understanding Pain mechanisms in KNEE osteoarthritis (UP-KNEE) study is a feasibility, double-blinded, placebo-controlled randomised parallel study in participants with radiographically defined knee OA and with self-reported chronic knee pain. The study involves the following assessments: (1) a suite of psychometric questionnaires; (2) quantitative sensory testing; (3) magnetic resonance imaging (MRI) scan of the knee and brain; (4) a 6-minute walk test; and (5) an intra-articular injection of bupivacaine or placebo (sodium chloride 0.9%) into the index knee. Assessments will be repeated post intra-articular injection apart from the MRI scan of the knee. Our aim is to provide proof of concept and descriptive statistics to power a future mechanistic trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Health Research Authority (HRA) (REC: 20/EM/0287). Results will be disseminated via peer-reviewed journals and scientific conferences. The results will also be shared with lay audiences through relevant channels, such as Pain Centre Versus Arthritis website and patient advocacy groups. TRIAL REGISTRATION NUMBER: NCT05561010.

Chronic postoperative pain after total knee arthroplasty: The potential contributions of synovitis, pain sensitization and pain catastrophizing-An explorative study.

BACKGROUND: A subset of osteoarthritis patients will experience chronic postoperative pain after total knee arthroplasty (TKA), but the source of pain is unclear. The aim of this exploratory study was to assess patients with and without postoperative pain after TKA using magnetic resonance imaging (MRI), quantitative sensory testing (QST), clinical assessment of pain and assessments of catastrophizing thoughts. METHODS: Forty-six patients completed the 6-month postoperative assessment. MRI findings were scored according to the MRI Osteoarthritis Knee Score recommendation for Hoffa synovitis, effusion size and bone marrow lesions. QST included assessment of pressure pain thresholds (PPTs), temporal summation of pain (TSP) and conditioned pain modulation (CPM). Pain catastrophizing was assessed using the Pain Catastrophizing Scale (PCS). Clinical pain assessment was conducted using a visual analogue scale (VAS, 0-10 cm), and groups of moderate-to-severe (VAS > 3) and none-to-mild postoperative pain (VAS ≤ 3) were identified. RESULTS: Patients with moderate-to-severe postoperative pain (N = 15) demonstrated higher grades of Hoffa synovitis (p < 0.001) and effusion size (p < 0.001), lower PPTs (p = 0.039), higher TSP (p = 0.001) and lower CPM (p = 0.014) when compared with patients with none-to-mild postoperative pain (N = 31). No significant difference was found in PCS scores between the two groups. Multiple linear regression models found synovitis (p = 0.036), effusion size (p = 0.003), TSP (p = 0.013) and PCS (p < 0.001) as independent parameters contributing to the postoperative pain intensity. CONCLUSION: These exploratory findings could indicate that chronic postoperative pain after TKA is a combination of joint-related synovitis and effusion, sensitization of central pain mechanisms and potentially pain catastrophizing thoughts, but larger studies are needed to confirm this. SIGNIFICANCE: The end-stage treatment of knee osteoarthritis is total knee arthroplasty. Some patients experience chronic postoperative pain after total knee arthroplasty, but the mechanism for chronic postoperative pain is widely unknown. The current study indicates that higher levels postoperative of synovitis and effusion, higher temporal summation of pain and higher pain catastrophizing scores could be associated with higher chronic postoperative pain.

Implant and patient survival rates using Exeter Trauma Stem hemiarthroplasty in fracture neck of femur patients: The largest study to date.

INTRODUCTION: Exeter Trauma Stems (ETS) femoral hemiarthroplasties are based on Exeter THR stems with a few design changes. Little has been published on ETS survival rates to justify their high cost compared to other cheaper implants. This is the largest prospective study to assess ETS implant failure-free survival rates in fracture neck of femur patients (NOF). This non-developing-centre study examined whether these design differences have altered implant survival (compared with Exeter THR's published survival data). METHODS: Data were prospectively collected by independent audit officers. Dislocation, periprosthetic fracture, re-admission with severe hip pain, deep infection and revision surgery were considered events of interest in implant failure-free survival. RESULTS: This study assessed 1,123 ETS stems (36 patients received bilateral ETS) in NOF patients. The mean patient age at the time of operation was 83 years (range; 49 - 102 years). The mean observation period was 2.5 years (range; 0 days - 8 years). Only 29 implants failed. All failure events were reported within the first year. Stem failure-free survival was 97.2% at eight years (CI 95.9% - 98%). Dislocation occurred in 10 patients (1%), periprosthetic femoral fracture in 4 (0.4%), and deep infection in 11 patients (1.2%). Patient survival rates were 75% and 48% at one and five years respectively. CONCLUSION: ETS has high implant failure-free survival rates when used in hip fractures. ETS design changes have not altered ETS survival when used in hip fractures compared with the published literature of Exeter THR stem when used as a treatment for OA. Exeter Trauma Stems in NOF patients might last these elderly patients their entire short lifetime.

A comparative analysis of multidimensional computerized adaptive testing for the DASH and QuickDASH scores in Dupuytren's disease.

The QuickDASH is a short-form version of the DASH questionnaire, the most widely used patient-reported outcome measure in hand surgery. Multidimensional computerized adaptive testing (MCAT) can produce shorter and more precise testing than static short forms, like QuickDASH. We used DASH responses from 507 patients with Dupuytren's disease to develop a MCAT. The algorithm was evaluated in a Monte Carlo simulation, where the standard error of measurement (SEm) of scores obtained from the 11-item QuickDASH was compared with scores obtained from an MCAT that could administer up to 11 items from the full 30-item DASH. The MCAT asked a mean of 8.51 items (SD 2.93) and 265/1000 simulated respondents needed to complete ≤five items. Median SEms were better for DASH MCAT: 0.299 (hand function) and 0.256 (sensory symptoms) versus 0.320 and 0.290, respectively, for QuickDASH. Our study showed that the DASH MCAT can produce more precise DASH measurement than the QuickDASH, from fewer items.

Development and in vitro assessment of a bi-layered chitosan-nano-hydroxyapatite osteochondral scaffold.

An innovative approach was developed to engineer a multi-layered chitosan scaffold for osteochondral defect repair. A combination of freeze drying and porogen-leaching out methods produced a porous, bioresorbable scaffold with a distinct gradient of pore size (mean = 160-275 µm). Incorporation of 70 wt% nano-hydroxyapatite (nHA) provided additional strength to the bone-like layer. The scaffold showed instantaneous mechanical recovery under compressive loading and did not delaminate under tensile loading. The scaffold supported the attachment and proliferation of human mesenchymal stem cells (MSCs), with typical adherent cell morphology found on the bone layer compared to a rounded cell morphology on the chondrogenic layer. Osteogenic and chondrogenic differentiation of MSCs preferentially occurred in selected layers of the scaffold in vitro, driven by the distinct pore gradient and material composition. This scaffold is a suitable candidate for minimally invasive arthroscopic delivery in the clinic with potential to regenerate damaged cartilage and bone.

Feedback to support examiners' understanding of the standard-setting process and the performance of students: AMEE Guide No. 145.

The ratings that judges or examiners use for determining pass marks and students' performance on OSCEs serve a number of essential functions in medical education assessment, and their validity is a pivotal issue. However, some types of errors often occur in ratings that require special efforts to minimise. Rater characteristics (e.g. generosity error, severity error, central tendency error or halo error) may present a source of performance irrelevant variance. Prior literature shows the fundamental problems in student performance measurement attached to judges' or examiners' errors. It also indicates that the control of such errors supports a robust and credible pass mark and thus, accurate student marks. Therefore, for a standard-setter who identifies the pass mark and an examiner who rates student performance in OSCEs, proper, user-friendly feedback on their standard-setting and ratings is essential for reducing bias. This feedback provides useful avenues for understanding why performance ratings may be irregular and how to improve the quality of ratings. This AMEE Guide discusses various methods of feedback to support examiners' understanding of the performance of students and the standard-setting process with an effort to make inferences from assessments fair, valid and reliable.

What Is Important to Patients Who Are Recovering From an Open Tibial Fracture? A Qualitative Study.

BACKGROUND: Open tibial fracture research has traditionally focused on surgical techniques; however, despite technological advances, outcomes from these injuries remain poor, with patients facing a sustained reduced quality of life. Research has rarely asked patients what is important to them after an open tibial fracture, and this question could potentially offer great insight into how to support patients. A qualitative study may assist in our understanding of this subject. QUESTIONS/PURPOSES: We asked: (1) What common themes did patients who have experienced open tibial fractures share? (2) What stresses and coping strategies did those patients articulate? (3) What sources for acquiring coping strategies did patients say they benefited from? METHODS: Semistructured interviews were conducted with patients who had sustained an open tibial fracture between January 1, 2016 and January 1, 2019. All participants were recruited from a Level 1 trauma center in England, and 26 participants were included. The mean age was 44 ± 17 years, and 77% (20 of 26) were men. The patients' injuries ranged in severity, and they had a range of treatments and complications. Transcripts were analyzed using framework analysis, with codes subsequently organized into themes and subthemes. RESULTS: Four themes were identified, which included recouping physical mobility, values around treatment, fears about poor recovery, and coping strategies to reduce psychological burden. Coping strategies were important in mitigating the psychological burden of injury. Task-focused coping strategies were preferred by patients and perceived as taking a proactive approach to recovery. Healthcare practitioners, and others with lived experience were able to educate patients on coping, but such resources were scant and therefore probably less accessible to those with the greatest need. CONCLUSION: Most individuals fail to return to previous activities, and it is unlikely that improvements in surgical techniques will make major improvements in patient outcomes in the near future. Investment in psychosocial support could potentially improve patient experience and outcomes. Digital information platforms and group rehabilitation clinics were identified as potential avenues for development that could offer individuals better psychosocial support with minimal additional burden for surgeons. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Short-Term Evaluation of Cellular Fate in an Ovine Bone Formation Model.

The ovine critical-sized defect model provides a robust preclinical model for testing tissue-engineered constructs for use in the treatment of non-union bone fractures and severe trauma. A critical question in cell-based therapies is understanding the optimal therapeutic cell dose. Key to defining the dose and ensuring successful outcomes is understanding the fate of implanted cells, e.g., viability, bio-distribution and exogenous infiltration post-implantation. This study evaluates such parameters in an ovine critical-sized defect model 2 and 7 days post-implantation. The fate of cell dose and behaviour post-implantation when combined with nanomedicine approaches for multi-model tracking and remote control using external magnetic fields is also addressed. Autologous STRO-4 selected mesenchymal stromal cells (MSCs) were labelled with a fluorescent lipophilic dye (CM-Dil), functionalised magnetic nanoparticles (MNPs) and delivered to the site within a naturally derived bone extracellular matrix (ECM) gel. Encapsulated cells were implanted within a critical-sized defect in an ovine medial femoral condyle and exposed to dynamic gradients of external magnetic fields for 1 h per day. Sheep were sacrificed at 2 and 7 days post-initial surgery where ECM was harvested. STRO-4-positive (STRO-4+) stromal cells expressed osteocalcin and survived within the harvested gels at day 2 and day 7 with a 50% loss at day 2 and a further 45% loss at 7 days. CD45-positive leucocytes were also observed in addition to endogenous stromal cells. No elevation in serum C-reactive protein (CRP) or non-haem iron levels was observed following implantation in groups containing MNPs with or without magnetic field gradients. The current study demonstrates how numbers of therapeutic cells reduce substantially after implantation in the repair site. Cell death is accompanied by enhanced leucocyte invasion, but not by inflammatory blood marker levels. Crucially, a proportion of implanted STRO-4+ stromal cells expressed osteocalcin, which is indicative of osteogenic differentiation. Furthermore, MNP labelling did not alter cell number or result in a further deleterious impact on stromal cells following implantation.

Comparison of rehabilitation interventions in nonoperatively treated distal radius fractures: a randomized controlled trial of effectiveness.

AIMS: Following cast removal for nonoperatively treated distal radius fractures, rehabilitation facilitated by advice leaflet and advice video were compared to a course of face-to-face therapy. METHODS: Adults with an isolated, nonoperatively treated distal radius fracture were included at six weeks post-cast removal. Participants were randomized to delivery of rehabilitation interventions in one of three ways: an advice leaflet; an advice video; or face-to-face therapy session(s). The primary outcome measure was the Disabilities of the Arm, Shoulder and Hand (DASH) score at six weeks post intervention and secondary outcome measures included DASH at one year, DASH work subscale, grip strength, and range of motion at six weeks and one year. RESULTS: A total of 116 (97%) of 120 enrolled participants commenced treatment. Of those, 21 were lost to follow-up, resulting in 30 participants in the advice leaflet, 32 in the advice video, and 33 face-to-face therapy arms, respectively at six weeks of follow-up. There was no significant difference between the treatment groups in the DASH at six weeks (advice leaflet vs face-to-face therapy, p = 0.69; advice video vs face-to-face therapy, p = 0.56; advice leaflet vs advice video, p = 0.37; advice leaflet vs advice video vs face-to-face therapy, p = 0.63). At six weeks, there were no differences in any secondary outcome measures except for the DASH work subscale, where face-to-face therapy conferred benefit over advice leaflet (p = 0.01). CONCLUSION: Following cast removal for nonoperatively treated distal radius fractures, offering an advice leaflet or advice video for rehabilitation gives equivalent patient-reported outcomes to a course of face-to-face therapy. Cite this article: Bone Joint J 2021;103-B(6):1033-1039.

Incidence and risk factors for poor ankle functional recovery, and the development and progression of posttraumatic ankle osteoarthritis after significant ankle ligament injury (SALI): the SALI cohort study protocol.

BACKGROUND: Ankle sprains are one of the most common musculoskeletal injuries, accounting for up to 5% of all Emergency Department visits in the United Kingdom. Ankle injury may be associated with future ankle osteoarthritis. Up to 70% of ankle osteoarthritis cases may be associated with previous ankle injury. There is limited research regarding the association between ankle sprain and ankle osteoarthritis development. The current study aims to phenotype those who suffer significant ankle ligament injuries, identify potential risk factors for ankle injuries and subsequent poor recovery, examine why individuals may develop osteoarthritis, and what factors influence this chance. METHODS: In this multicentre cohort study participants were recruited from nine Emergency Departments and two Urgent Care Centres in the United Kingdom. Participants (aged 18-70 years old) were defined as those who had suffered an isolated acute ankle sprain, which was Ottawa Ankle Rules positive, but negative for a significant ankle fracture on x-ray. Age and sex matched controls were also recruited. The controls were individuals who had not suffered a significant ankle injury, including ankle pain, function affected for more than 7 days, or the ankle caused them to report to an Emergency Department. Data is collected through a series of seven questionnaires (at baseline, 3 months, 1 year, 3 years, 5 years, 10 years, and 15 years later). The questionnaires include four sections (demographic questions; index injury, and injury history questions; functional assessment questions; and quality of life questions) and are designed to collect detailed information about the individual, their injury, potential risk factors for ankle sprains and ankle osteoarthritis, plus their medical history and any medication consumed. DISCUSSION: The Significant Ankle Ligament Injury (SALI) study aims to add to the limited knowledge regarding which factors can predict ankle sprains, complaints, and osteoarthritis. This is important because despite ankle sprains being regarded as a benign injury that resolves quickly, residual symptoms are not uncommon months and years after the injury.

Risk Factors for Knee Osteoarthritis in Retired Professional Footballers: A Cross-Sectional Study.

OBJECTIVE: To determine risk factors for 3 knee osteoarthritis (KOA) outcomes, knee pain (KP), radiographic KOA (RKOA), and total knee replacement (TKR) in professional footballers. DESIGN: This was a cross-sectional study involving a postal questionnaire, followed by radiographic assessment in a subcohort of responders. SETTINGS AND PARTICIPANTS: Four thousand seven hundred seventy-five questionnaires were sent to retired professional footballers, who had played in the English football league, and 1207 responded. Of these, 470 underwent knee radiographs. ASSESSMENT OF RISK FACTORS: Potential factors include age, body mass index (BMI), knee alignment, a history of football-related knee injury, and training hours (during career) were collected through the questionnaire. MAIN OUTCOME MEASURES: Knee osteoarthritis outcomes were current KP (pain for most days of the previous month), TKR (self-reported), and RKOA (observed through radiographs). RESULTS: Football-related injury was the strongest risk factor for KP [adjusted odds ratio (aOR), 4.22; 95% confidence interval (CI), 3.26-5.48], RKOA [aOR, 2.88; 95% CI, 1.81-4.59], and TKR [aOR, 4.83; 95% CI, 2.87-8.13]. Footballers had a 7% increased risk of RKOA for every 1000 hours trained. Although age and gout were associated with all 3 KOA outcomes, BMI, nodal osteoarthritis (OA), a family history of OA, knee malalignment, and 2D:4D ratio were associated with one or another of these 3 KOA outcomes. CONCLUSION: This study is the first to examine KOA risk factors in retired professional footballers. The study has identified several risk factors, both specific (eg, knee injury and training dose) and nonspecific (eg, age and gout) to footballers. This may be used to develop prevention strategies to reduce the risk of KOA in professional footballers after retirement.

Self-reported sports injuries and later-life health status in 3357 retired Olympians from 131 countries: a cross-sectional survey among those competing in the games between London 1948 and PyeongChang 2018.

OBJECTIVE: Describe the self-reported prevalence and nature of Olympic-career injury and general health and current residual symptoms in a self-selected sample of retired Olympians. METHODS: 3357 retired Olympians from 131 countries completed a cross-sectional online survey, distributed by direct email through World Olympians Association and National Olympian Associations databases. The survey captured Olympic sport exposure, significant training and competition injury history (lasting >1 month), general health (eg, depression) during the athlete's career, and current musculoskeletal pain and functional limitations. RESULTS: 55% were men (44% women, 1% unknown), representing 57 sports (42 Summer, 15 Winter), aged 44.7 years (range 16-97). A total of 3746 injuries were self-reported by 2116 Olympians. This equated, 63.0% (women 68.1%, men 59.2%) reporting at least one significant injury during their Olympic career. Injury prevalence was highest in handball (82.2%) and lowest in shooting (40.0%) for Summer Olympians; and highest in alpine skiing (82.4%) and lowest in biathlon (40.0%) for Winter Olympians. The knee was the most frequently injured anatomical region (20.6%, 120 median days severity), followed by the lumbar spine (13.1%, 100 days) and shoulder/clavicle (12.9%, 92 days). 6.6% of Olympians said they had experienced depression during their career. One-third of retired Olympians reported current pain (32.4%) and functional limitations (35.9%). CONCLUSIONS: Almost two-thirds of Olympians who completed the survey reported at least one Olympic-career significant injury. The knee, lumbar spine and shoulder/clavicle were the most commonly injured anatomical locations. One-third of this sample of Olympians attributed current pain and functional limitations to Olympic-career injury.

The predictive value of quantitative sensory testing: a systematic review on chronic postoperative pain and the analgesic effect of pharmacological therapies in patients with chronic pain.

Studies have suggested that quantitative sensory testing (QST) might hold a predictive value for the development of chronic postoperative pain and the response to pharmacological interventions. This review systematically summarizes the current evidence on the predictive value of QST for chronic postoperative pain and the effect of pharmacological interventions. The main outcome measures were posttreatment pain intensity, pain relief, presence of moderate-to-severe postoperative pain, responders of 30% and 50% pain relief, or validated questionnaires on pain and disability. A systematic search of MEDLINE and EMBASE yielded 25 studies on surgical interventions and 11 on pharmacological interventions. Seventeen surgical and 11 pharmacological studies reported an association between preoperative or pretreatment QST and chronic postoperative pain or analgesic effect. The most commonly assessed QST modalities were pressure stimuli (17 studies), temporal summation of pain (TSP, 14 studies), and conditioned pain modulation (CPM, 16 studies). Of those, the dynamic QST parameters TSP (50%) and CPM (44%) were most frequently associated with chronic postoperative pain and analgesic effects. A large heterogeneity in methods for assessing TSP (n = 4) and CPM (n = 7) was found. Overall, most studies demonstrated low-to-moderate levels of risk of bias in study design, attrition, prognostic factors, outcome, and statistical analyses. This systematic review demonstrates that TSP and CPM show the most consistent predictive values for chronic postoperative pain and analgesic effect, but the heterogeneous methodologies reduce the generalizability and hence call for methodological guidelines.

High mortality following revision hip arthroplasty for periprosthetic femoral fracture.

AIMS: To determine mortality risk after first revision total hip arthroplasty (THA) for periprosthetic femoral fracture (PFF), and to compare this to mortality risk after primary and first revision THA for other common indications. METHODS: The study cohort consisted of THAs recorded in the National Joint Registry between 2003 and 2015, linked to national mortality data. First revision THAs for PFF, infection, dislocation, and aseptic loosening were identified. We used a flexible parametric model to estimate the cumulative incidence function of death at 90 days, one year, and five years following first revision THA and primary THA, in the presence of further revision as a competing risk. Analysis covariates were age, sex, and American Society of Anesthesiologists (ASA) grade. RESULTS: A total of 675,078 primary and 74,223 first revision THAs were included (of which 6,131 were performed for PFF). Following revision for PFF, mortality ranged from 9% at 90 days, 21% at one year, and 60% at five years in the highest risk group (males, ≥ 75 years, ASA ≥ 3) to 0.6%, 1.4%, and 5.5%, respectively, for the lowest risk group (females, < 75 years, ASA ≤ 2). Mortality was greater in all groups following first revision THA for PFF than for primary THA. Compared to mortality risk after first revision THA for infection, dislocation, or aseptic loosening, revision for PFF was associated with higher five-year mortality in all groups except males < 75 years with an ASA ≤ 2. CONCLUSION: Mortality risk after revision THA for PFF is high, reaching 60% at five years in the highest risk patient group. In comparison to other common indications for revision, PFF demonstrated the highest overall risk of mortality at five years. These estimates can be used in the surgical decision-making process and when counselling patients and carers regarding surgical risk. Cite this article: Bone Joint J 2020;102-B(12):1670-1674.

Intra-articular Injection Administration in UK Ex-professional Footballers During Their Playing Careers and the Association with Post-career Knee Osteoarthritis.

BACKGROUND: The long-term risk from knee intra-articular (KIA) injections in professional athletes such as ex-footballers remains unknown. The use of KIA injections is controversial and remains anecdotally prolific as it is perceived as being safe/beneficial. The aim of this study was to determine the number, type and frequency KIA injections administered to retired professional footballers during their playing careers and the associations with post-career knee osteoarthritis (KOA). METHODS: This is a cross-sectional study involving a postal questionnaire (n = 1207) and subsequent knee radiographs in a random sample of questionnaire responders (n = 470). Footballers self-reported in the questionnaire whether they had received KIA injections and the estimated total number over the course of their playing career. Participant characteristics and football career-related details were also recorded. KOA was measured as self-reported knee pain (KP), total knee replacement (TKR) and radiographic KOA (RKOA). RESULTS: 44.5% of footballers had received at least one KIA injection (mean: 7.5; SD ± 11.2) during their professional career. 71% of knee injections were cortisone/corticosteroid based. Multivariate logistic regression, adjusting for age, body mass index (BMI) and significant knee injury identified that footballers with injections were two times more likely to have KP (OR 1.81, 95% CI 1.40-2.34) and TKR (OR 2.21, 95% CI 1.43-3.42) than those without injections. However, there was no association with RKOA (OR 1.30, 95% CI 0.85-2.01). Given, the association with KP and TKR, we found a significant dose-response relationship as the more injections a player received (by dose-response groups), the greater the risk of KP and TKR outcomes after adjustment for knee injury and other confounders (p for trend < 0.01). CONCLUSION: On average, 8 KIA injections were given to the ex-footballers during their professional career. The most commonly administered injections were cortisone based. These injections associated with KP and TKR after they retired. The associations are independent of knee injuries and are dose dependent. The study suggests that there may have been excessive use of KIA injections to expedite return to play and this contributed to detrimental long-term outcomes such as KP and TKR post-retirement from professional football.

Formulating injectable pastes of porous calcium phosphate glass microspheres for bone regeneration applications.

Current trends in regenerative medicine treatments for bone repair applications focus on cell-based therapies. These aim to deliver the treatment via a minimally invasive injection to reduce patient trauma and to improve efficacy. This paper describes the injectability of porous calcium phosphate glass microspheres to be used for bone repair based on their formulation, rheology and flow behavior. The use of excipients (xanthan gum, methyl cellulose and carboxyl methyl cellulose) were investigated to improve flow performance. Based on our results, the flow characteristics of the glass microsphere pastes vary according to particle size, surface area, and solid to liquid ratio, as well as the concentration of viscosity modifiers used. The optimal flow characteristics of calcium phosphate glass microsphere pastes was found to contain 40 mg/mL of xanthan gum which increased viscosity whilst providing elastic properties (∼29,000 Pa) at shear rates that mirror the injection process and the resting period post injection, preventing the glass microspheres from both damage and dispersion. It was established that a base formulation must contain 1 g of glass microspheres (60-125 µm in size) per 1 mL of cell culture media, or 0.48 g of glass microspheres of sizes between 125 and 200 µm. Furthermore, the glass microsphere formulations with xanthan gum were readily injectable via a syringe-needle system (3-20 mL, 18G and 14G needles), and have the potential to be utilized as a cell (or other biologics) delivery vehicle for bone regeneration applications.

Porous Phosphate-Based Glass Microspheres Show Biocompatibility, Tissue Infiltration, and Osteogenic Onset in an Ovine Bone Defect Model.

Phosphate-based glasses (PBGs) are bioactive and fully degradable materials with tailorable degradation rates. PBGs can be produced as porous microspheres through a single-step process, using changes in their formulation and geometry to produce varying pore sizes and interconnectivity for use in a range of applications, including biomedical use. Calcium phosphate PBGs have recently been proposed as orthobiologics, based on their in vitro cytocompatibility and ion release profile. In this study, porous microspheres made of two PBG formulations either containing TiO2 (P40Ti) or without (P40) were implanted in vivo in a large animal model of bone defect. The biocompatibility and osteogenic potential of these porous materials were assessed 13 weeks postimplantation in sheep and compared to empty defects and autologous bone grafts used as negative and positive controls. Histological analysis showed marked differences between the two formulations, as lower trabeculae-like interconnection and higher fatty bone marrow content were observed in the faster degrading P40-implanted defects, while the slower degrading P40Ti material promoted dense interconnected tissue. Autologous bone marrow concentrate (BMC) was also incorporated within the P40 and P40Ti microspheres in some defects; however, no significant differences were observed in comparison to microspheres implanted alone. Both formulations induced the formation of a collagen-enriched matrix, from 20 to 40% for P40 and P40Ti2.5 groups, suggesting commitment toward the bone lineage. With the faster degrading P40 formulation, mineralization of the tissue matrix was observed both with and without BMC. Some lymphocyte-like cells and foreign body multinucleated giant cells were observed with P40Ti2.5, suggesting that this more durable formulation might be linked to an inflammatory response. In conclusion, these first in vivo results indicate that PBG microspheres could be useful candidates for bone repair and regenerative medicine strategies and highlight the role of material degradation in the process of tissue formation and maturation.