Development of Biodegradable Polyurethane Scaffolds Using Amino Acid and Dipeptide-Based Chain Extenders for Soft Tissue Engineering

Abstract

The inherent flexibility of polyurethane (PU) chemistry allows the incorporation of specific chemical moieties into the backbone structure conferring a unique biological function to these synthetic polymers. We describe here the synthesis and characterization of a PU containing a Gly-Leu linkage, the cleavage site of several matrix metalloproteinases. A Gly-Leu dipeptide was introduced into the chain extender of the polyurethane through the reaction with 1,4-cyclohexane dimethanol. PUs synthesized with the Gly-Leu-based chain extender had a high weight-average molecular weight (M(w) > 125 x 10(3)) and were phase segregated, semi-crystalline polymers with a low soft-segment glass-transition temperature (T(g) < -50 degrees C). Uniaxial tensile testing of PU films indicated that the polymer could withstand high ultimate tensile strengths (approx. 13 MPa) and were flexible with breaking strains of approx. 900%. The Gly-Leu PU had a significantly higher initial modulus, yield stress and ultimate stress compared to a PU previously developed in our laboratory containing a phenylalanine-based chain extender (Phe PU). The Gly-Leu-based chain extender allowed for better hard segment packing and hydrogen bonding leading to enhanced mechanical properties. Electrospinning was used to form scaffolds with randomly organized fibers and an average fiber diameter of approx. 3.6 mum for both the Gly-Leu and Phe PUs. Mouse embryonic fibroblasts were successfully cultured on the PU scaffolds out to 28 days. Further investigations into cell-mediated polymer degradation will help to identify the suitability of this new biomaterial as scaffolds for soft tissue applications.