James B. Richardson

Autologous chondrocyte implantation for cartilage repair: monitoring its success by magnetic resonance imaging and histology

Autologous chondrocyte implantation is being used increasingly for the treatment of cartilage defects. In spite of this, there has been a paucity of objective, standardised assessment of the outcome and quality of repair tissue formed. We have investigated patients treated with autologous chondrocyte implantation (ACI), some in conjunction with mosaicplasty, and developed objective, semiquantitative scoring schemes to monitor the repair tissue using MRI and histology. Results indicate repair tissue to be on average 2.5 mm thick. It was of varying morphology ranging from predominantly hyaline in 22% of biopsy specimens, mixed in 48%, through to predominantly fibrocartilage, in 30%, apparently improving with increasing time postgraft. Repair tissue was well integrated with the host tissue in all aspects viewed. MRI scans provide a useful assessment of properties of the whole graft area and adjacent tissue and is a noninvasive technique for long-term follow-up. It correlated with histology (P = 0.02) in patients treated with ACI alone.

Articular cartilage: structure, injuries and review of management

INTRODUCTION Chondral and osteochondral injuries are commonly seen in todays clinical practice. Articular cartilage provides an ultimate low-friction gliding surface, which none of the artificial constructs have been able to replace successfully. Retrospective review of the knee arthroscopies has revealed an underestimated incidence of this complex problem. Cartilage injuries in the knee joint if left untreated lead to pre-mature early arthritis and affect the activities of daily living. Various different treatment methods of cartilage regeneration have shown encouraging results, but unfortunately none has proved to be the ultimate solution. SOURCES OF DATA This article re-visits the intricate structure of articular cartilage and reviews the different methods of regeneration described in the literature, based on evidence-based effectiveness. The methods described by their originators and their results are considered gold standards for those methods, as being the best available evidence. AREAS OF AGREEMENT Majority of the authors agree that cartilage injuries are complex and difficult to treat. If untreated, cartilage defects lead to early osteoarthritis. Great debate still persists about the best available treatment for symptomatic chondral or osteochondral defect(s). AREAS OF CONTROVERSY The controversy about the management outplays its aetiological theories. Several authors have reported good results with different techniques; however none has proved to be the solution for the problem. GROWING POINTS Up until 1990, marrow stimulation techniques were routine form of management for chondral defects. However, ever since autologous chondrocyte implantation was successfully introduced in humans, it has provided a new dimension for the treatment of chondral defects. AREAS TIMELY FOR DEVELOPING RESEARCH The success of any treatment lies in its longevity. The new minimally invasive techniques are being invented. However, timely research, on the basis of randomized controlled trial comparing different methods of cartilage reconstruction is necessary for decision-making in todays evidence-based medical world.

Updates on stem cells and their applications in regenerative medicine

Stem cells have the capacity for self‐renewal and capability of differentiation to various cell lineages. Thus, they represent an important building block for regenerative medicine and tissue engineering. These cells can be broadly classified into embryonic stem cells (ESCs) and non‐embryonic or adult stem cells. ESCs have great potential but their use is still limited by several ethical and scientific considerations. The use of bone marrow‐, umbilical cord‐, adipose tissue‐, skin‐ and amniotic fluid‐derived mesenchymal stem cells might be an adequate alternative for translational practice. In particular, bone marrow‐derived stem cells have been used successfully in the clinic for bone, cartilage, spinal cord, cardiac and bladder regeneration. Several preclinical experimental studies are under way for the application of stem cells in other conditions where current treatment options are inadequate. Stem cells can be used to improve healthcare by either augmenting the bodys own regenerative potential or developing new therapies. This review is not meant to be exhaustive but gives a brief outlook on the past, present and the future of stem cell‐based therapies in clinical practice. Copyright

A clinical review of cartilage repair techniques

Chondral injuries involving the knee are common. In a recent study of 993 consecutive arthroscopies scored using the International Cartilage Repair Society (ICRS) knee evaluation form,[1][1] articular cartilage pathology was found in 66% of patients, while 11% had localised, full-thickness lesions

Repair of human articular cartilage after implantation of autologous chondrocytes

Tissue engineering is an increasingly popular method of addressing pathological disorders of cartilage. Recent studies have demonstrated its clinical efficacy, but there is little information on the structural organisation and biochemical composition of the repair tissue and its relation to the adjacent normal tissue. We therefore analysed by polarised light microscopy and immunohistochemistry biopsies of repair tissue which had been taken 12 months after implantation of autologous chondrocytes in two patients with defects of articular cartilage. Our findings showed zonal heterogeneity throughout the repair tissue. The deeper zone resembled hyaline-like articular cartilage whereas the upper zone was more fibrocartilaginous. The results indicate that within 12 months autologous chondrocyte implantation successfully produces replacement cartilage tissue, a major part of which resembles normal hyaline cartilage.

Immunohistochemical study of collagen types I and II and procollagen IIA in human cartilage repair tissue following autologous chondrocyte implantation

This study has assessed the relative proportions of type I and II collagens and IIA procollagen in full depth biopsies of repair tissue in a large sample of patients treated with autologous chondrocyte implantation (ACI). Sixty five full depth biopsies were obtained from knees of 58 patients 8–60 months after treatment by ACI alone (n = 55) or in combination with mosaicplasty (n = 10). In addition articular cartilage was examined from eight individuals (aged 10–50) as controls. Morphology and semi-quantitative immunohistochemistry for collagen types I and II and procollagen IIA in the repair tissue were studied. Repair cartilage thickness was 2.89 ± 1.5 mm and there was good basal integration between the repair cartilage, calcified cartilage and subchondral bone. Sixty five percent of the biopsies were predominantly fibrocartilage (mostly type I collagen and IIA procollagen), 15% were hyaline cartilage (mostly type II collagen), 17% were of mixed morphology and 3% were fibrous tissue (mostly type I collagen). Type II collagen and IIA procollagen were usually found in the lower regions near the bone and most type II collagen was present 30–60 months after treatment. The presence of type IIA procollagen in the repair tissue supports our hypothesis that this is indicative of a developing cartilage, with the ratio of type II collagen:procollagen IIA increasing from < 2% in the first two years post-treatment to 30% three to five years after treatment. This suggests that cartilage repair tissue produced following ACI treatment, is likely to take some years to mature.

Birmingham hip resurfacing: THE PREVALENCE OF FAILURE

Despite the increasing interest and subsequent published literature on hip resurfacing arthroplasty, little is known about the prevalence of its complications and in particular the less common modes of failure. The aim of this study was to identify the prevalence of failure of hip resurfacing arthroplasty and to analyse the reasons for it. From a multi-surgeon series (141 surgeons) of 5000 Birmingham hip resurfacings we have analysed the modes, prevalence, gender differences and times to failure of any hip requiring revision. To date 182 hips have been revised (3.6%). The most common cause for revision was a fracture of the neck of the femur (54 hips, prevalence 1.1%), followed by loosening of the acetabular component (32 hips, 0.6%), collapse of the femoral head/avascular necrosis (30 hips, 0.6%), loosening of the femoral component (19 hips, 0.4%), infection (17 hips, 0.3%), pain with aseptic lymphocytic vascular and associated lesions (ALVAL)/metallosis (15 hips, 0.3%), loosening of both components (five hips, 0.1%), dislocation (five hips, 0.1%) and malposition of the acetabular component (three hips, 0.1%). In two cases the cause of failure was unknown. Comparing men with women, we found the prevalence of revision to be significantly higher in women (women = 5.7%; men = 2.6%, p < 0.001). When analysing the individual modes of failure women had significantly more revisions for loosening of the acetabular component, dislocation, infection and pain/ALVAL/metallosis (p < 0.001, p = 0.004, p = 0.008, p = 0.01 respectively). The mean time to failure was 2.9 years (0.003 to 11.0) for all causes, with revision for fracture of the neck of the femur occurring earlier than other causes (mean 1.5 years, 0.02 to 11.0). There was a significantly shorter time to failure in men (mean 2.1 years, 0.4 to 8.7) compared with women (mean 3.6 years, 0.003 to 11.0) (p < 0.001).

Autologous chondrocyte implantation with bone grafting for osteochondral defect due to posttraumatic osteonecrosis of the hip- : a case report

Copyright© Taylor & Francis 2006. ISSN 1745–3674. Printed in Sweden – all rights reserved. DOI 10.1080/17453670610046208 A 31-year-old man sustained a severe fracture dislocation of the left hip as a result of a road traffic accident in 2001. There was a subcapital fracture of the femoral head with complete separation of the head from the femoral neck, and posterior wall fracture of the acetabulum (Figure 1). The initial management was open reduction and internal fixation, and the immediate postoperative radiograph showed the screws to be in a satisfactory position within the femoral head. After 1 year, the patient was walking with one crutch and the range of movement of the left hip was restricted due to severe pain. At this time, his hip score (HS) was 52 of a possible 100 (Harris 1969). Radiography demonstrated a united femoral fracture, but the fixation screws had penetrated the hip joint due to collapse of the osteonecrotic femoral head, and there was narrowing of the joint space (Figure 2). Taking the young age of the patient into account, we decided to proceed with autologous chondrocyte implantation (ACI). The first stage was performed 21 months after the original injury. During an arthroscopy of the ipsilateral knee, 240 mg of macroscopically normal full depth cartilage was harvested from the low load area of the medial trochlea. The tissue was transported to a dedicated clinical cell culture laboratory for isolation and expansion of the chondrocytes as previously

Isolation and Characterisation of Mesenchymal Stem Cells from Different Regions of the Human Umbilical Cord

Umbilical cords as a source of stem cells are of increasing interest for cell therapies as they present little ethical consideration and are reported to contain immune privileged cells which may be suitable for allogeneic based therapies. Mesenchymal stem cells (MSCs) sourced from several different cord regions, including artery, vein, cord lining, and Whartons jelly, are described in the literature. However, no one study has yet isolated and characterised MSCs from all regions of the same cord to determine the most suitable cells for cell based therapeutics.

Fracture stiffness measurement in the assessment and management of tibial fractures.

Fracture stiffness results obtained from patients with tibial fractures treated with external skeletal fixation are reviewed. A threshold value of bending fracture stiffness at which removal of the external fixator and functional loading of the fracture can be prescribed is proposed to be 15 N m degree(-1). The logarithm of the bending stiffness was found to give a linear relationship with time post-fracture, thus implying that stiffness increases exponentially with time. From three previous studies of mechanical measurements of fracture healing, the fracture stiffnesses at which independent weight-bearing was permitted were determined and were found to be comparable with the threshold value of stiffness proposed in this paper. A review of previously published data for the in-vivo stiffness of intact tibiae showed that the stiffness required for functional healing of a tibial fracture is between 17 and 25% of that of the intact tibia.