Development of biodegradable adhesives for meniscus repair

Abstract

Menisci are crucial structures in the knee joint as they play functions in load transfer, maintaining joint stability and in homeostasis of articular cartilage. Most injuries of the knee are associated with meniscus trauma; the meniscus tears which lead to pain, swelling and locking of the joint. Current treatment methods do not bring fully satisfactory results. The ultimate goal of the PhD project was to develop novel tissue adhesives (glues) for repair of meniscal tears. Such glues, once deposited in meniscal tear, fill the tear, bind to meniscus tissue and hold the torn region together during the healing period. Within this project, we have designed and developed biodegradable tissue adhesives composed of biocompatible polymers: trimethylene carbonate (TMC), polyethylene glycol (PEG) and citric acid (CA). These copolymers were finally end-functionalized with isocyanate groups in order to achieve strong covalent attachment of the glues to meniscus tissue as well as curing of the glue in the wet environment of the knee joint. The developed materials were tested in terms of both their chemical structure and physical, mechanical and adhesive properties. Moreover, their biocompatibility was evaluated in vitro in cellular assays and bovine meniscus explants culture. Furthermore, materials were implanted in rats, in order to evauate their biocompatibility and degradation profile in vivo. The obtained results showed satisfactory adhesive strength of the glues to meniscus tissue, which was significantly higher than that of adhesives used nowadays in clinics. In vitro cellular tests as well as explant tissue culture confirmed that the materials were not toxic to the cells. The results of the in vivo implantation are showed moderate inflammatory response, which is expected to be less prominent when applied in physiologically relevant amounts in a meniscus tissue. Moreover, the materials proved to be biodegradable with degradation profile suitable for meniscus repair application. The developed tissue glues hold great potentials to be applied for meniscal tear repair as a replace or support for sutures and staples. They have satisfactory both mechanical, adhesive, and biological properties.