Introduction

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).

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.

Aim: Concerns have been expressed that DMARDS may interfere with bone healing. Previous studies give conflicting advise and no consensus exist in current practise especially with the newer DMARDS such as Leflunomide, Etanercept, and Infliximab. The aim of this study was to assess the in-vitro effect of DMARDS and cox-2 inhibitors on Osteoblast activity.

Method: Osteoblasts were cultured from femoral heads obtained from five young otherwise healthy patients undergoing total hip replacement The cells were cultured using techniques that have been previously described. A computer aided design of experiment was used as a model for setting up the experiment on samples obtained from the five patients. Normal therapeutic concentration of the various DMARDS was added alone and in combination to the media. The cell growth was estimated after two weeks using spectrophotometric technique using Roche Cell proliferation Kit. Multiple regression analysis was used to estimate the best predictor of the final result.

Results: The most significant factor (p< 0.001) in predicting the ultimate response was the patient themselves. Cox-2 inhibitor (Etoricoxib) was found to have the most consistent effect although always in combination with some other drug which varied amogst different patients. Etoricoxib in fact had a stimulatory effect (R=0.219) on the osteoblast growth.

Conclusion: Different patients respond differently to the drugs. None of the DMARDS tested inhibit osteoblast proliferation and differentiation in-vitro. If osteoblastic activity is considered to be the primary factor responsible for bone healing, then an inhibition should not result in patients who are on these drugs.

Introduction: Before proceeding to long-term studies, we studied early clinical results of combined Autologous Chondrocyte Implantation (ACI) and Allogenic Meniscus Transplantation (AMT). Meniscus deficient knees develop early osteo-arthritis (OA) of the knee joint. Autologous Cartilage Implantation (ACI) is contraindicated in case of meniscus deficient knees. And on contrary the Allogenic Meniscus Transplantation (AMT) is contraindicated in cartilage defects in the knee joint. But a combination of the two procedures for bone on bone OA might be a solution for this problem. This was the main purpose of our study.

Methods: We studied a consecutive series of eight patients (7 males and 1 female), with an average age= 43 years (29–58), presenting with painful secondary arthritis, due to premature loss of meniscus and chondral defect/s. Median size of the femoral defects was 8.16 cm2 and of the tibial side 2.69 cm2 All patients were treated with a combination of Autologous Chondrocyte implantation (ACI) and Allogenic Meniscus Transplantation (AMT). Chondral defects were covered with periosteum/ Chondroguide membrane, secured in place with in-vitro cultured autologous chondrocytes injected underneath the path. Meniscus placed as load-bearing washer on the surface of ACI of tibia. ACI rehabilitation protocol followed post-operatively. Assessment at the end of one year was done with self-assessed Lysholm score, histology and the MRI scan.

Results: Mean pre-operaive Lysholm score was 49 (17–75). This increased to a mean of 66 (26–87) at 1 year, an average increase of 16.4 points. Average one-year satisfaction score was 3 and they were back to all active life style. Five out of eight patients showed significant functional improvement at last post-operative follow-up (2 to 6 years; mean of 3.2 years). Complications were aseptic synovitis in 3 cases. Three failures were noted showig persistant pain and swelling in one, rupture of meniscus in second and third patient had a knee replacement. Arthroscopy at 1 year showed a stable meniscus with all healed peripheral margins in all except in one case with some thinning with no evidence of rejection. Histology of meniscus showed a fibrocartilage well populated with viable cells and the peripheral zone was well vascularised and integrated with capsule. Biopsy of ACI site was predominantly of fibrocartilage with good basal integration with subchondral bone. On MRI scan, allogenic meniscus was well integrated with capsule along the line of repair, showing foci of variable signal intensities within the meniscus. There was no evidence of meniscal subluxation in all but one case showing mild extrusion. ACI graft site showed a varied appearance, with 3 grafts showing focal grade 3to 4 changes.

Conclusion: Seven out of eight patients improved post-operatively at one year, in terms of pain relief and increased activity. It’s possible to combine these two techniques together. Short-term outcomes are satisfactory. We could not find any deleterious effects of combining these two techniques together. So we conclude that, this might act as a one step towards a biological knee replacement.

Background: Articular cartilage injuries are very common. Small defects don’t heal on their own and large defects can’t regenerate new cartilage. This would largely be due to the fact that chondrocytes are embedded in a firm and tough matrix and hence can’t migrate to the defect site to regenerate a new cartilage tissue. So ultimate fate is patient getting early osteoarthritis. Cartilage defects in the knee may be symptomatic and cause pain, swelling and catching. There are several different surgical procedures available to treat cartilage injuries, but no method has been judged superior. The ultimate aim of the treatment is restoration of normal knee function by regeneration of hyaline cartilage in the defect, and to achieve a complete integration to the surrounding cartilage and underlying bone. Arthroscopic debridement and lavage may give symptomatic relief for a limited time. Autologous Chondrocytes Implantation (ACI) was first described in 1994. Encouraging primary results were reported, and further research was promoted. Long-term results are encouraging. ACI is being done in Robert Jones & Agnes Hunt orthopaedic Hospital, Oswestry since last 8 years.

Methods: We studied a cohort of first 118 patients who underwent ACI for knee joint in this institute, focussing on their mid-term results. Patients having chondral defects were offered ACI. They all were explained the procedure and informed written consent was obtained. Patients filled in a self-assessed Lysholm forms before the operation. They also underwent pre-operative MRI scan of knee joint. ACI procedure consisted of three stages— Stage I —Arthroscopic harvest biopsy of cartilage and chondrocytes culture in lab. Stage II—Arthrotomy of the knee. The defect edges were freshened, covered by periosteum or chondroguide, which was sutured to the cartilage with 6-0 vicryl. Chondrocytes were injected underneath this patch. Post-op CPM and Physiotherapy. Stage III—1-year arthroscopic surgery. Assessment was done with Lysholm score, MRI scan, histological and arthroscopic analysis. Patients were followed up clinically thereafter with yearly Lysholm scores.

Results: 118 patients with an average age of 35 years (15–59) underwent ACI for knee in last 8 years. 93 patients had single defect, 24 had multiple (> 1) chondral defects, with mean area 4.81 cm2. MRI showed a good integration of defect with surrounding cartilage with varied signal intensities. About 55–56% patients underwent some or other form of trimming, which improved immediate results. However only 50 % of these were symptomatic. Defects on MFC did well as compared to other sites, followed by on trochlea. Defects on patella showed poor results, though the number is less for comparison. Total 79 specimens of 1-year histology showed good healing with formation of fibrocartilage (40), mixed (20) and hyaline (8), fibrous tissue (6), bone in 1 case and inconclusive in 2 cases. Mean pre-op Lysholm score was 50.16. Average score at one year was found to be 69.52.

Conclusion: Results of ACI are encouraging. Patients continued to improve slowly over a period of time, achieving maximum function between one and 2 years post-surgery. Our study showed that there after their scores remained static.

Methotrexate and Cox-2 inhibitors are thought to interfere with bone healing. There have been controversial results published in the literature. The effect of newer antirheumatoids (Leflunomide, Etanercept, Infliximab) has not been studied. The aim of this study was to find the in-vitro effect of methotrexate, newer anti-rheumatoids, steroids and cox-2 inhibitors on Osteoblasts. Osteoblasts were cultured from femoral heads obtained from young otherwise healthy patients undergoing total hip replacement. The cells were cultured using techniques that have been previously described. A computer aided design of experiment was used as a model for setting up the experiment on samples obtained from five patients. Normal therapeutic concentration of the various antirheumatoids was added alone and in combination to the media. The cell growth was estimated after two weeks using spectrophotometric technique using Roche Cell proliferation Kit. Multiple regression analysis was done to estimate the best predictor of the final result. Patient was found to be the most significant factor (p< 0.001) in predicting the ultimate response. Cox-2 inhibitor (Etoricoxib) was found to be the next best predictor (p=0.043). Etoricoxib in fact had a stimulatory effect (R=0.219) on the osteoblast growth, which was accentuated in the presence of other agents that varied amongst different patients. Different patients respond differently to the drugs. None of the antirheumatoids inhibit osteoblast proliferation and differentiation in-vitro. If osteoblastic activity is considered to be the primary factor responsible for bone healing, then an inhibition should not result in patients who are on these drugs.

Background: Growth and development of the intervertebral disc and its adjacent vertebrae is regulated via relative levels of cell proliferation, cell death and hypertrophy, and through extracellular matrix synthesis or degradation [1]. The synthesis of matrix molecules in the growing spine of embryonic rats has been reported in some detail [2,3]. In addition, increased levels of apoptotic disc cell death have been described in normal ageing, disc degeneration and in a murine model of disc spondylosis [4,5]. However, levels of cell proliferation in the developing spine have not been formally investigated.

Methods/Results: BALB/c mice were injected with the thymidine analogue, bromodeoxyuridine (BrdU), at weeks 1–4 postnatally and killed 1 or 24 hours later. The lumbar spines were decalcified and tissue sections immunostained for BrdU-incorporation. The intervertebral disc was fully formed at weeks 1–4, consisting of a notochordal nucleus pulposus, lamellar anulus fibrosus, and cartilaginous endplates between the disc and vertebral growth-plates. BrdU-immunopositivity was most marked in 1 week old mice, particularly in the proliferative zone of the growth-plate and the apophyseal ring. By 4 weeks, few, if any, BrdU-labelled cells were present in the disc, but some positivity remained in the apophyses. There were more paired BrdU-labelled cells at 24 hours than 1 hour post-injection in all regions, indicating likely clonal growth of these cells.

Conclusions: Cell proliferation forms an important part of the growth of the vertebrae, but also features in the early postnatal growth of the murine intervertebral disc. An understanding of how proliferation in these cell populations is regulated will help augment repair and regenerative responses in damaged adult discs or scoliosis.

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.

We have measured the effect of age on the rate of outgrowth of cells from human trabecular bone, using a quantitative dye-binding technique. In cultures supplemented with autologous serum, there were significant negative correlations between the age of the donor and both the proportion of fragments from which outgrowths were seen after 7 days (r = -0.70; p < 0.001) and the total cell number after 14 days (r = -0.78; p < 0.005). The autologous serum supported greater cell proliferation than did fetal calf serum in all subjects regardless of age. Taken with previous observations that the in vitro growth kinetics of passaged human bone cells are independent of age, our results show that the number of proliferative precursor cells on trabecular-bone surfaces is higher in younger subjects. There is a marked decrease in precursor numbers in the second and third decades of life to a level which is maintained into old age.