Biodegradable hydrogels by physical and enzymatic crosslinking of biomacromolecules

Abstract

Cartilage can be damaged due to trauma or diseases like osteoarthritis. These damages cause pain and impair normal articulation of the joint. Current strategies like microfracture, mosaicplasty and autologous chondrocyte implantation for cartilage repair relieve pain and improve joint function but it has been shown that these procedures only lead to a temporary solution. The newly formed tissue often lacks the properties of native cartilage and shows signs of deterioration after 1 year. An alternative approach to cartilage repair is tissue engineering. Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences towards the reconstruction or development of biological substitutes that restore, maintain or improve tissue functions 1. In tissue engineering generally scaffolds are used to provide a stable temporary matrix for cells in order to grow new tissue. Since a hydrogel is a material that closely resembles the natural environment of cells in cartilage, research in tissue engineering of cartilage has mainly focused on these materials to act as a temporary matrix. Although many materials have been designed and prepared to form hydrogels several issues still have to be tackled. One of these issues is the adhesion of hydrogels to the surrounding tissue at the implant site. Hereto we have performed a fundamental study of the effects of incorporating positively charged moieties in amphiphilic block copolymers on their aggregation and (thermo-reversible) gelation behavior and on the formation of physically crosslinked hydrogels. The rationale is to increase the adhesion properties of physically crosslinked hydrogels to soft tissues like cartilage that have an ECM that is negatively charged. Furthermore, we have studied the influence of the chemical structure and aggregation behavior of tyramine substituted synthetic and natural polymers on their enzymatic crosslinking, an ongoing research subject in our group. Research was aimed at developing injectable and biodegradable scaffolds with controlled degradation times, which support chondrocyte survival and matrix production