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.

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.

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.

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.

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.

ACL and meniscal injuries increase the risk of primary total knee replacement for osteoarthritis: a matched case-control study using the Clinical Practice Research Datalink (CPRD).

OBJECTIVES: The aim of this study was to investigate whether ACL injury (ACLi) or meniscal injury increases the risk of end-stage osteoarthritis (OA) resulting in total knee replacement (TKR). METHODS: A matched case-control study of all TKRs performed in the UK between January 1990 and July 2011 and recorded in the Clinical Practice Research Datalink (CPRD) was undertaken. The CPRD contains longitudinal data on approximately 3.6 million patients. Two controls were selected for each case of TKR, matched on age, sex and general practitioner location as a proxy for socioeconomic status. Individuals with inflammatory arthritis were excluded. The odds of having TKR for individuals with a CPRD-recorded ACLi were compared with those without ACLi using conditional logistic regression, after adjustment for body mass index, previous knee fracture and meniscal injury. The adjusted odds of TKR in individuals with a recorded meniscal injury compared with those without were calculated. RESULTS: After exclusion of individuals with inflammatory arthritis, there were 49 723 in the case group and 104 353 controls. 153 (0.31%) cases had a history of ACLi compared with 41 (0.04%) controls. The adjusted OR of TKR after ACLi was 6.96 (95% CI 4.73 to 10.31). 4217 (8.48%) individuals in the TKR group had a recorded meniscal injury compared with 669 (0.64%) controls. The adjusted OR of TKR after meniscal injury was 15.24 (95% CI 13.88 to 16.69). CONCLUSION: This study demonstrates that ACLi is associated with a sevenfold increased odds of TKR resulting from OA. Meniscal injury is associated with a 15-fold increase odds of TKR for OA.

Development and validation of self-reported line drawings of the modified Beighton score for the assessment of generalised joint hypermobility.

BACKGROUND: The impracticalities and comparative expense of carrying out a clinical assessment is an obstacle in many large epidemiological studies. The purpose of this study was to develop and validate a series of electronic self-reported line drawing instruments based on the modified Beighton scoring system for the assessment of self-reported generalised joint hypermobility. METHODS: Five sets of line drawings were created to depict the 9-point Beighton score criteria. Each instrument consisted of an explanatory question whereby participants were asked to select the line drawing which best represented their joints. Fifty participants completed the self-report online instrument on two occasions, before attending a clinical assessment. A blinded expert clinical observer then assessed participants' on two occasions, using a standardised goniometry measurement protocol. Validity of the instrument was assessed by participant-observer agreement and reliability by participant repeatability and observer repeatability using unweighted Cohen's kappa (k). Validity and reliability were assessed for each item in the self-reported instrument separately, and for the sum of the total scores. An aggregate score for generalised joint hypermobility was determined based on a Beighton score of 4 or more out of 9. RESULTS: Observer-repeatability between the two clinical assessments demonstrated perfect agreement (k 1.00; 95% CI 1.00, 1.00). Self-reported participant-repeatability was lower but it was still excellent (k 0.91; 95% CI 0.74, 1.00). The participant-observer agreement was excellent (k 0.96; 95% CI 0.87, 1.00). Validity was excellent for the self-report instrument, with a good sensitivity of 0.87 (95% CI 0.81, 0.91) and excellent specificity of 0.99 (95% CI 0.98, 1.00). CONCLUSIONS: The self-reported instrument provides a valid and reliable assessment of the presence of generalised joint hypermobility and may have practical use in epidemiological studies.

Home-based pre-surgical psychological intervention for knee osteoarthritis (HAPPiKNEES): a feasibility randomized controlled trial.

OBJECTIVE: To determine the feasibility of conducting a trial of a pre-surgical psychological intervention on pain, function, and mood in people with knee osteoarthritis listed for total knee arthroplasty. DESIGN: Multi-centre, mixed-methods feasibility randomized controlled trial of intervention plus usual care versus usual care. SETTING: Participants' homes or hospital. PARTICIPANTS: Patients with knee osteoarthritis listed for total knee arthroplasty and score >7 on either subscales of Hospital Anxiety and Depression Scale. INTERVENTION: Up-to 10 sessions of psychological intervention (based on cognitive behavioural therapy). MAIN MEASURES: Feasibility outcomes (recruitment and retention rates, acceptability of trial procedures and intervention, completion of outcome measures), and standardized questionnaires assessing pain, function, and mood at baseline, and four and six months post-randomisation. RESULTS: Of 222 people screened, 81 did not meet inclusion criteria, 64 did not wish to participate, 26 were excluded for other reasons, and 51 were randomized. A total of 30 completed 4-month outcomes and 25 completed 6-month outcomes. Modal number of intervention sessions completed was three (range 2-8). At 6-month follow-up, mood, pain, and physical function scores were consistent with clinically important benefits from intervention, with effect sizes ranging from small ( d = 0.005) to moderate ( d = 0.74), and significant differences in physical function between intervention and usual care groups ( d = 1.16). Feedback interviews suggested that participants understood the rationale for the study, found the information provided adequate, the measures comprehensive, and the intervention acceptable. CONCLUSION: A definitive trial is feasible, with a total sample size of 444 people. Pain is a suitable primary outcome, but best assessed 6 and 12 months post-surgery.

Factors associated with pain and osteoarthritis at the hip and knee in Great Britain's Olympians: a cross-sectional study.

BACKGROUND: Knowledge of the epidemiology and potentially modifiable factors associated with musculoskeletal disease is an important first step in injury prevention among elite athletes. AIM: This study investigated the prevalence and factors associated with pain and osteoarthritis (OA) at the hip and knee in Great Britain's (GB) Olympians aged 40 and older. METHODS: This is a cross-sectional study. A survey was distributed to 2742 GB Olympians living in 30 countries. Of the 714 (26.0%) who responded, 605 were eligible for analysis (ie, aged 40 and older). RESULTS: The prevalence of hip and knee pain was 22.4% and 26.1%, and of hip and knee OA was 11.1% and 14.2%, respectively. Using a multivariable model, injury was associated with OA at the hip (adjusted OR (aOR) 10.85; 95% CI 3.80 to 30.96) and knee (aOR 4.92; 95% CI 2.58 to 9.38), and pain at the hip (aOR 5.55; 95% CI 1.83 to 16.86) and knee (aOR 2.65; 95% CI 1.57 to 4.46). Widespread pain was associated with pain at the hip (aOR 7.63; 95% CI 1.84 to 31.72) and knee (aOR 4.77; 95% CI 1.58 to 14.41). Older age, obesity, knee malalignment, comorbidities, hypermobility and weight-bearing exercise were associated with hip and knee OA and/or pain. CONCLUSIONS: This study detected an association between several factors and hip and knee pain/OA in retired GB Olympic athletes. These associations require further substantiation in retired athletes from other National Olympic Committees, and through comparison with the general population. Longitudinal follow-up is needed to investigate the factors associated with the onset and progression of OA/pain, and to determine if modulation of such factors can reduce the prevalence of pain and OA in this population.

A web-based survey to identify current practice in skeletal pin site management.

Infections associated with percutaneous pins and wires are common complications which can have a significant impact on patient outcomes. A survey was undertaken to identify current practice and gain insight into variations of clinical practice. Invitations were sent by email to complete an electronic questionnaire using SurveyMonkey. The survey was left open for 100 days. The single largest group of respondents (37.4%, n = 120) cleansed pin sites daily, with significant differences identified between medical and nursing professions (P = 0.02), and country of practice (P < 0.001). Significant differences were also identified in the use of different cleansing solutions between medical and nursing professions (P < 0.001) and country (P < 0.001). The majority group preferences were saline 30% (n = 96) and alcoholic chlorhexidine 29.6% (n = 95). Pin site crusts were routinely removed by 57.9% (n = 186). Pin sites were left exposed by 50.3% (n = 160). Dry gauze was identified as the most common dressing used to dress pin sites, however, substantial variation was identified in the types of dressings used. Compression was not routinely applied to pin sites by 51.6% (n = 165). There remains considerable diversity of practice when caring for pin sites. Further research is required to identify the most effective methods in preventing pin site infection.

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.

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.

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.

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.

The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain.

BACKGROUND: Clinical studies of osteoarthritis (OA) suggest central sensitization may contribute to the chronic pain experienced. This preclinical study used the monosodium iodoacetate (MIA) model of OA joint pain to investigate the potential contribution of spinal sensitization, in particular spinal glial cell activation, to pain behaviour in this model. Experimental OA was induced in the rat by the intra-articular injection of MIA and pain behaviour (change in weight bearing and distal allodynia) was assessed. Spinal cord microglia (Iba1 staining) and astrocyte (GFAP immunofluorescence) activation were measured at 7, 14 and 28 days post MIA-treatment. The effects of two known inhibitors of glial activation, nimesulide and minocycline, on pain behaviour and activation of microglia and astrocytes were assessed. RESULTS: Seven days following intra-articular injection of MIA, microglia in the ipsilateral spinal cord were activated (p < 0.05, compared to contralateral levels and compared to saline controls). Levels of activated microglia were significantly elevated at day 14 and 21 post MIA-injection. At day 28, microglia activation was significantly correlated with distal allodynia (p < 0.05). Ipsilateral spinal GFAP immunofluorescence was significantly (p < 0.01) increased at day 28, but not at earlier timepoints, in the MIA model, compared to saline controls. Repeated oral dosing (days 14-20) with nimesulide attenuated pain behaviour and the activation of microglia in the ipsilateral spinal cord at day 21. This dosing regimen also significantly attenuated distal allodynia (p < 0.001) and numbers of activated microglia (p < 0.05) and GFAP immunofluorescence (p < 0.001) one week later in MIA-treated rats, compared to vehicle-treated rats. Repeated administration of minocycline also significantly attenuated pain behaviour and reduced the number of activated microglia and decreased GFAP immunofluorescence in ipsilateral spinal cord of MIA treated rats. CONCLUSIONS: Here we provide evidence for a contribution of spinal glial cells to pain behaviour, in particular distal allodynia, in this model of osteoarthritic pain. Our data suggest there is a potential role of glial cells in the central sensitization associated with OA, which may provide a novel analgesic target for the treatment of OA pain.

Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain.

OBJECTIVE: To investigate the impact of an experimental model of osteoarthritis (OA) on spinal nociceptive processing and the role of the inhibitory endocannabinoid system in regulating sensory processing at the spinal level. METHODS: Experimental OA was induced in rats by intraarticular injection of sodium mono-iodoacetate (MIA), and the development of pain behavior was assessed. Extracellular single-unit recordings of wide dynamic range (WDR) neurons in the dorsal horn were obtained in MIA-treated rats and saline-treated rats. The levels of endocannabinoids and the protein and messenger RNA levels of the main synthetic enzymes for the endocannabinoids (N-acyl phosphatidylethanolamine phospholipase D [NAPE-PLD] and diacylglycerol lipase α [DAGLα]) in the spinal cord were measured. RESULTS: Low-weight (10 gm) mechanically evoked responses of WDR neurons were significantly (P < 0.05) facilitated 28 days after MIA injection compared with the responses in saline-treated rats, and spinal cord levels of anandamide and 2-arachidonoyl glycerol (2-AG) were increased in MIA-treated rats. Protein levels of NAPE-PLD and DAGLα, which synthesize anandamide and 2-AG, respectively, were elevated in the spinal cords of MIA-treated rats. The functional role of endocannabinoids in the spinal cords of MIA-treated rats was increased via activation of cannabinoid 1 (CB(1) ) and CB(2) receptors, and blockade of the catabolism of anandamide had significantly greater inhibitory effects in MIA-treated rats compared with control rats. CONCLUSION: Our findings provide new evidence for altered spinal nociceptive processing indicative of central sensitization and for adaptive changes in the spinal cord endocannabinoid system in an experimental model of OA. The novel control of spinal cord neuronal responses by spinal cord CB(2) receptors suggests that this receptor system may be an important target for the modulation of pain in OA.