Disability and slow return to sport and work after tendon rupture are major challenges. Platelet Rich Plasma (PRP) is an autologous supraphysiological concentration of platelets from whole blood that has demonstrated positive cellular and physiological effects on healing in laboratory conditions but evidence from adequately powered robust clinical trials is lacking. We aimed to determine the clinical efficacy of PRP for treatment of acute Achilles tendon rupture. In a placebo-controlled, participant- and assessor-blinded, trial at 19 NHS hospitals we randomly assigned 230 adults starting acute Achilles rupture non-surgical management to PRP injection or dry-needle insertion (placebo) to the rupture gap under local anaesthetic. Patients with confounding or contraindicated concurrent medical conditions were excluded. The primary outcome was muscle-tendon function, assessed by the limb symmetry index (LSI, uninjured limb/injured limb × 100, higher scores better) of the work (Joules) performed during the heel-rise endurance test at 24 weeks. Secondary outcomes were: Achilles Tendon Rupture Score (ATRS, 0–100, higher scores better), quality of life (SF-12), pain, and goal attainment. Trial registration: ISRCTN54992179Background
Methods
The objectives of the study were to investigate demographic, injury and surgery/treatment-associated factors that could influence clinical outcome, following Autologous Chondrocyte Implantation (ACI) in a large, “real-world”, 20 year longitudinally collected clinical data set. Multilevel modelling was conducted using R and 363 ACI procedures were suitable for model inclusion. All longitudinal post-operative Lysholm scores collected after ACI treatment and before a second procedure (such as knee arthroplasty but excluding minor procedures such as arthroscopy) were included. Any patients requiring a bone graft at the time of ACI were excluded. Potential predictors of ACI outcome explored were age at the time of ACI, gender, smoker status, pre-operative Lysholm score, time from surgery, defect location, number of defects, patch type, previous operations, undergoing parallel procedure(s) at the time of ACI, cell count prior to implantation and cell passage number. The best fit model demonstrated that for every yearly increase in age at the time of surgery, Lysholm scores decreased by 0.2 at 1-year post-surgery. Additionally, for every point increase in pre-operative Lysholm score, post-operative Lysholm score at 1 year increased by 0.5. The number of cells implanted also impacted on Lysholm score at 1-year post-op with every point increase in log cell number resulting in a 5.3 lower score. In addition, those patients with a defect on the lateral femoral condyle (LFC), had on average Lysholm scores that were 6.3 points higher one year after surgery compared to medial femoral condyle (MFC) defects. Defect grade and location was shown to affect long term Lysholm scores, those with grade 3 and patella defects having on average higher scores compared to patients with grade 4 or trochlea defects. Some of the predictors identified agree with previous reports, particularly that increased age, poorer pre-operative function and worse defect grades predicted poorer outcomes. Other findings were more novel, such as that a lower cell number implanted and that LFC defects were predicted to have higher Lysholm scores at 1 year and that patella lesions are associated with improved long-term outcomes cf. trochlea lesions.
To determine whether platelet-rich plasma (PRP) injection improves outcomes two years after acute Achilles tendon rupture. A randomized multicentre two-arm parallel-group, participant- and assessor-blinded superiority trial was undertaken. Recruitment commenced on 28 July 2015 and two-year follow-up was completed in 21 October 2019. Participants were 230 adults aged 18 years and over, with acute Achilles tendon rupture managed with non-surgical treatment from 19 UK hospitals. Exclusions were insertion or musculotendinous junction injuries, major leg injury or deformity, diabetes, platelet or haematological disorder, medication with systemic corticosteroids, anticoagulation therapy treatment, and other contraindicating conditions. Participants were randomized via a central online system 1:1 to PRP or placebo injection. The main outcome measure was Achilles Tendon Rupture Score (ATRS) at two years via postal questionnaire. Other outcomes were pain, recovery goal attainment, and quality of life. Analysis was by intention-to-treat.Aims
Methods
Tantalum trabecular metal components are increasingly used to reconstruct major bone defects in revision arthroplasty surgery. It is known that some metals such as silver have antibacterial properties. Recent reports have raised the question as to whether Tantalum components are protective against infection in revision surgery. This is based on a retrospective, single institution review, of revision cases comparing tantalum with titanium acetabular implants, which reported a lower incidence of subsequent infection in the tantalum group. This laboratory study aimed to establish if tantalum had any intrinsic antibacterial properties against planktonic bacteria or ability to inhibit biofilm formation. Equal sized pieces of tantalum (Trabecular metal, Zimmer UK) and titanium (Trilogy, Zimmer UK) were sterilised and then incubated with a low dose inoculum of either Staphylococcus aureus or Staphylococcus epidermidis for 24 hours. After serial dilution, colony forming units were quantified on MH agar plates. To establish the ability to inhibit biofilm formation these tantalum and titanium pieces were then washed twice, sonicated and washed again to remove loosely adhered planktonic bacteria. They were then re-incubated for 24 hours prior to quantifying colony forming units. All experiments were performed in triplicateIntroduction
Materials and methods
Randomised controlled study evaluating new bone formation Regenerating new bone by cell therapy could provide therapeutic options in many conditions such as fracture non-unions and osteo-chondral defect regeneration in advance OA. In this randomised controlled study we evaluated the efficacy of new bone formation by bone marrow derived stromal cells (BMSC) in patients with non-union.Summary
Introduction
To evaluate the efficacy of bone marrow derived stromal cells (BMSC) for the treatment of non-unions in fractures. An ethically approved single centre randomised control trial recruited 35 patients for treatment of non-unions with BMSC during 2006–2010. Autologous BMSC were culture expanded at the Good Manufacturing Practice (GMP) standard Oscell® laboratory in the hospital. Following Aim
Methods
Meniscus deficiency leads to the development of early arthritis. Total knee replacement may be the only available treatment option in certain situations. However it is generally best avoided in young patients. We hypothesized that a combination of the two procedures, Allograft Meniscal Transplantation (AMT) and Autologous Chondrocyte Implantation (ACI) would be a solution to treat bone-on-bone arthritis in meniscal deficient knees and postpone the need for a total knee replacement (TKR). 12 consecutive patients who underwent both ACI and AMT between 1998 and 2005 were followed up prospectively. The patients were assessed by a self-assessed Lysholm score prior to the procedure and yearly thereafter. All operations were performed by the senior author (JBR). ACI procedure was performed according to the standard technique. Frozen meniscal allograft with bone plugs at either ends secured by sutures in the bone tunnels. Post operatively all patients underwent a strict Oscell Rehabilitation protocol. A repeat procedure or progression to a TKR was taken as a failure.Introduction
Materials/Methods
Platelet-Rich Plasma (PRP), an autologous derivative of whole blood that contains a supraphysiological concentration of platelets and growth factors. Most published studies have investigated the effect of PRP-conditioned media on cell cultures. We are not aware of any study that has investigated whole PRP with its cellular components on human tissue cultures. This study aims to investigate the effect of PRP on cell migration from human Achilles tendon explants, and the subsequent cellular proliferative effects in culture. This is an Purpose
Methods
Regenerative medicine is a rapidly expanding discipline. However due to a lack of validated outcome measures, clinical trials have been far few. This study aims to assess the validity, inter-observer reliability and intra-observer reproducibility of experimental fracture healing assessment on plain radiographies. This technique involves implantation of mesenchymal stem cell (MSC) seeded constructs on only one side of the fracture after randomisation. We examined inter/intraobserver agreement on the area and “bridging length” of callus formed on opposite sides of the fracture. Among 16 orthopaedic surgeons with trauma commitments (8 consultants, 8 registrars) on two separate occasions (average 52 days apart). They independently assessed the radiographs (AP or lateral) of 28 patients with fractures of the tibial or femoral shaft. The fractures chosen included non-unions treated with MSC/constructs and fresh fractures at 4–9 months. For each radiograph the assessor assigned which side (medial or lateral) is there more callus. Chase-corrected agreement using Fleiss kappa was used to compare opinions. Digital analysis software (Image-J) was used to quantify extent/bridging callus and correlate it with surgeons opinion.Introduction
Methods
Platelet Rich Plasma (PRP) has been shown to have positive effect in tendon regeneration in in-vitro and limited in-vivo animal studies. We aim to study PRP use in acute Achilles tendon rupture (ATR) regeneration in a purposely designed clinical trial. This is a prospective double-arm patient-blinded randomized controlled trial. ATR patients were randomized into PRP treatment or control groups. Non-operatively treated patients received PRP or control injection in clinic. In operatively treated patients, PRP gel was applied in the ruptured gap during percutaneous repair. Standard rehabilitation protocol was used and patients were followed up for 24 weeks. ATR, VISA-A and FAOS scores were used as subjective outcome measures. Functional ultrasound Elastography (FUSE) was performed at each follow-up to assess the mechanical properties of tendons. PRP analysis and tendon needle-biopsy were performed to study the histological differences during healing in both groups.Purpose
Methods
Autologous Chondrocyte Implantation (ACI) is frequently used to treat chondral defects in the knee with a good long-term outcome. This is contraindicatd in meniscal deficient knees. Allogenic Menicsal Transplantation (AMT) has been shown to give good symptomatic relief in meniscus deficient knees. However this is contraindicated in advanced cartilage degeneration. We hypothesized that combination of these two might be a solution for bone-on-bone arthritis in young individuals. We studied a consecutive series of 12 patients who underwent combined ACI and AMT between 1998 and 2005. Pre operative and post operative comparisons of lysholm scores were recorded. Magnetic Resonance Imaging was performed to assess the integration ACI & AMT. Arthroscopy was performed at one year for assessment and obtain biopsy for histological examination.Background
Methods
Autologous Chondrocyte Implantation (ACI) is a procedure which is gaining acceptance for the treatment of cartilage defects in the knee with good results and a long term durable outcome. Its use in other joints has been limited, mainly to the ankle. We aimed to assess the outcome of ACI in the treatment of chondral and osteochondral defects in the hip. Fifteen patients underwent ACI for chondral or osteochondral defects in the femoral head with a follow up of upto 8 years (mean of 2 years) in our institution with a mean age of 37 years at the time of operation. Pre-operatively hip function was assessed by using the Harris Hip Score and MRI. Post-operatively these were repeated at 1 year and hip scores repeated annually. Failure was defined as a second ACI to the operated lesion or a conversion to a hip resurfacing or replacement.Background
Methods
A new surgical hybrid technique involving the combination of autologous bone plug(s) and autologous chondrocyte implantation (AOsP-ACI) was used and evaluated as a treatment option in 15 patients for repair of large osteochondral defects in knee (N=12) and hip joints (N=3). Autologous Osplugs were used to contour the articular surface and the autologous chondrocytes were injected underneath a biological membrane covering the plug. The average size of the osteochondral defects treated was 4.5cm2. The average depth of the bone defect was 26mm. The patients had a significant improvement in their clinical symptoms at 12 months with significant increase in the Lysholm Score and Harris Hip Score (p = 0.031). The repaired tissue was evaluated using Magnetic Resonance Imaging, Computerised Tomography, arthroscopy, histology and immunohistochemistry (for expression of type I and II collagen). Magnetic Resonance Imaging, Computerised Tomography and histology at 12 months revealed that the bone plug became well integrated with the host bone and repair cartilage. Arthroscopic examination at 12 months revealed good lateral integration of the AOsP-ACI with the surrounding cartilage. Immunohistochemistry revealed mixed fibro-hyaline cartilage. We conclude that the hybrid AOsP-ACI technique provides a promising surgical approach for the treatment of patients with large osteochondral defects. This study highlights the use of this procedure in two different weightbearing joints and demonstrates good early results which are encouraging. The long term results need to be evaluated.
We aimed to assess the long term results of patients who underwent Autologous Chondrocyte Implantation (ACI) for osteochondral lesions of the talus. Between 1998 and 2006, 28 patients underwent ACI for osteochondral lesions of the talus. All these patients were prospectively reviewed and assessed for long term results. Outcomes were assessed using satisfaction scores, Mazur ankle score and the AOFAS score, and Lysholm knee score for donor site morbidity. The 28 patients who underwent the procedure included 18 males and 10 females. Follow up ranged from 1–9 years. In all patients, there was an improvement in the Mazur and AOFAS ankle scores and the Lysholm scores showed minimal donor site morbidity. Improvement in ankle score was independent of age and gender. The better the pre-op score the less the difference in post-op ankle scores. Patients were unlikely to benefit with pre-op ankle scores over 75. The mid to long term results of ACIs in the treatment of localised, contained cartilage defects of the talus are encouraging and prove that it is a satisfactory treatment modality for symptomatic osteochondral lesions of the talus. Complications are limited. However, in view of limited number of patients, a multi-centre randomised controlled study is required for further assessment.
The patients were admitted for harvesting of stromal stem cells by bone marrow aspiration from the iliac bone. BMSSC were expanded in tissue cultures for three weeks to an average of 5 x 106 cells. After successful culture the non-union site underwent decortication and BMSSC added to synthetic bone substitute (different types) on one side of the fracture (medial or lateral) according to randomisation. The side of treatment was blinded to patient, surgeons and radiologist. Standard radiographs were taken and evaluated independently by three experienced musculoskeletal radiologists. The extent of callus formation on each side was recorded. In equivocal cases computerized tomography (CT) was also obtained.
During the first stage knee arthroscopy using a superolateral approach, the cartilage specimens were taken from a minor load bearing area of either the central or superolateral trochlea using a 5mm gouge. Clinical outcomes were assessed using a patient satisfaction score and the Lysholm knee score, taken both pre- and post- operatively at 3 months and annually thereafter.
The mean Lysholm score preoperatively was 98/100. Postoperatively eight patients had a reduced score (mean reduction 14) at twelve months follow up. In those patients with new knee symptoms at one year, analysis of the Lysholm score components showed the Locking and Limp categories to be the most frequent cause of a reduced score. Two patients had repeat knee arthroscopy at 18 months and 2 years postoperatively for symptoms of catching, anterior knee pain and swelling.
The procedure of cartilage harvest from the trochlea of the knee has an associated donor site morbidity which is present at one year. Ninety two percent of patients were pleased or extremely pleased with their ACI procedure, despite the requirement of surgery on their knee and it would seem that the amount of early knee morbidity these patients experience is outweighed by the improvement in symptoms in the treated joint. Ideally to optimise cartilage repair less morbid techniques to obtain cartilage need to be identified or alternatively mesenchymal stem cells could be used as an alternative source, which has already had limited success in the knee and might also be applied to other joints.
Patients with osteochondral lesions of the talus have traditionally been difficult to treat. Autologous chondrocyte implantion (ACI) may provide predictable repair through restoring an articular surface. We reviewed our results of Ankle ACI in eight ACI plus two ACI and mosaicplasty combined with an average age of 40 years (32 to 62) performed over four years. The patients were assessed with a modified Mazur ankle score, patient satisfaction score and Lysholm knee score, pre- and post-operatively. Ankle arthroscopic assessment was performed in patients at 12 months post surgery. The average time to follow up was 24 months (range two to 52). The osteochondral lesions were post traumatic in seven cases, with seven lesions situated medially and three anterolaterally. The average size of the talar defects at surgery was 2.25cm (range 1 to 4 cm.) Patient satisfaction scores in eight patients were either “extremely pleased” or “pleased” with the operation which was sustained in the patients at up to four years follow up. The Mazur scores increased by 23 points at mean 24 months follow up. Six patients with over 12 months follow up maintained a markedly improved ankle score. Patients were noted to rehabilitate twice as quickly as patients receiving ACI to the knee. The Lysholm knee scores returned to the preoperative level in four patients, with the remaining six patients showing a reduced score (mean 12 points), suggesting there may be some donor site morbidity. Five had ankle arthroscopy at one year and were shown to have filled defects and stable cartilage. A biopsy taken from the graft site showed hyaline like cartilage and fibrocartilage to be present These early results suggest that ankle ACI is an appropriate treatment for large symptomatic osteochondral lesions in the talus.
