thesis

A novel method of articular cartilage repair.

Abstract

Articular cartilage repair of post-traumatic articular cartilage defects and well-defined articular cartilage pathology is challenging in clinical practice and has been the focus of investigations for many years. In the present thesis a newly developed polymer system, based on poly-ethyl-methacrylate PEMA polymer and tetra-hydro-furfuryl methacrylate THFMA monomer has been exploited for the repair of large, full-thickness articular cartilage defects, created in a weight-bearing surface in the rabbit knee joint. The method of implantation is simple and easily reproducible and can be performed in one stage with open arthrotomy or arthroscopy in clinical applications. Intravenous administration of the monomer did not elicit significant cardiorespiratory side effects. The repair tissue in defects treated with PEMA/THFMA was compared to control defects that healed 'naturally'. Macroscopic and histological/histochemical evaluation using the newly developed Articular Cartilage Repair Scoring System, immunohistochemistry, electron microscopy, image analysis as well as biochemical analysis were used for the characterisation of the repair tissue. The results demonstrated that the PEMA/THFMA polymer enhanced significantly the quality of repair up to 1 year postoperatively. The repair tissue contained numerous chondrocytes producing large amounts of proteoglycans and collagen type II, and it was completely bonded to the adjacent normal articular cartilage in the vast majority of the specimens. The enhancing effect of PEMA/THFMA in articular cartilage defects was also demonstrated in three age groups of rabbits at 6 weeks, thus increasing the potential clinical applications of the polymer. Furthermore, PEMA/THFMA was compared to the conventional bone cement PMMA/MMA. At 6 weeks post-implantation PEMA/THFMA produced significantly superior repair tissue, compared to PMMA/MMA, confirming the importance of the properties of the new polymer. Finally, PEMA/THFMA was exploited as a potential drug delivery system in vivo by loading human growth hormone in the polymer. It was shown that the loaded polymer repaired the defects with a proliferative type of tissue, resembling immature articular cartilage

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