Polymeric Biomaterials with Degradation Sites for Proteases Involved in Cell Migration

Abstract

A new class of biodegradable polymeric biomaterials is described which exhibits degradation by specific enzymes that are localized near cell surfaces during cell migration. These materials are telechelic BAB block copolymers of the water-soluble biocompatible polymer poly(ethylene glycol) (the A block, abbreviated PEG hereafter) and short oligopeptides that are cleavage sequences for targeted enzymes (the B block). These copolymers are further capped at each end with reactive acrylate groups to allow polymerization to form cross-linked hydrogel networks. Two materials were synthesized, one specifically degraded by collagenase and the other by plasmin. The incorporation of peptides that induce cell adhesion to similar materials has been previously reported. The combination of these two types of bioactive signals (one for cell-mediated degradation, one for cell adhesion) into one material should achieve a biomimetic polymeric hydrogel with properties of natural extracellular matrix (also a polymeric hydrogel, although of biological origin), while still affording the advantages of a synthetic polymer. These materials are expected to have numerous applications in wound healing and tissue engineering.