IN SITU CROSSLINKABLE SYNTHETIC EXTRACELLULAR MATRICES FOR TISSUE ENGINEERING AND REPAIR

Abstract

We recently developed a novel approach to the creation of a fully synthetic, covalently crosslinked extracellular matrix (sECM). This material may be crosslinked in situ in the presence of cells to provide an injectable cell-seeded hydrogel for tissue repair, or with drugs in a controlled-release format. Chemical modification of hyaluronan (HA), other glycosaminoglycans (GAGs), proteins, or other carboxylate-containing polymers with thiol residues creates macromonomers that can be crosslinked with biocompatible electrophiles. First, we show in vitro and in vivo growth of healthy cellularized tissues using films, sponges, and hydrogels based on the sECM technology. Second, we extend the use of the in situ crosslinkable sECM to the growth for the in vivo repair of cartilage and bone defects and for the healing of tympanic membrane perforations. Third, we describe the use of biointeractive, crosslinked heparin-containing GAG dressings for controlled release of bFGF and re-epithelializaion of full-thickness wounds in a diabetic mouse model of chronic wound healing. Finally, we illustrate the use of in situ crosslinkable HA-derived hydrogels, with and without covalently linked antiproliferatives, for prevention of abdominal surgical adhesions for scar-free healing following sinus surgery.