Recent advances in tissue synthesis in vivo by use of collagen-glycosaminoglycan copolymers

Abstract

Biologically active analogues of the extracellular matrix (ECM) are synthesized by grafting glycosaminoglycan (GAG) chains onto type I collagen, and by controlling the physicochemical properties of the resulting graft copolymer. Collagen-GAG ECM analogues have previously been shown to induce regeneration of the dermis in humans and the guinea pig, and of the rat sciatic nerve. Current studies have emphasized elucidation of the molecular mechanism through which tissue-specific ECM analogues induce regeneration. The contribution of the GAGs to the biological activity of the skin regeneration template was confirmed by studying the contribution of several GAGs to the inhibition of wound contraction in guinea pigs. The interaction between cells and the porous structure of an ECM analogue was studied with emphasis on the deformation of pores which occurs during wound contraction. The synthesis of scar, as well as of partly regenerated tissue which has a morphology between that appropriate for scar and for normal dermis, was quantitatively assayed for the first time using a laser light scattering technique. An ECM analogue which has been shown to be capable of inducing regeneration of functional sciatic nerve in the rat over a gap larger than 10 mm was incorporated in the design of a biodegradable implant for peripheral nerve regeneration.