Rational design of poly(peptide-ester) block copolymers for enzyme-specific surface resorption.

Abstract

Tissue resorption and remodeling are pivotal steps in successful healing and regeneration, and it is important to design biomaterials that are responsive to regenerative processes in native tissue. The cell types responsible for remodeling, such as macrophages in the soft tissue wound environment and osteoclasts in the bone environment, utilize a class of enzymes called proteases to degrade the organic matrix. Many hydrophobic thermoplastics used in tissue regeneration are designed to degrade and resorb passively through hydrolytic mechanisms, leaving the potential of proteolytic-guided degradation underutilized. Here, we report the design and synthesis of a tyrosol-derived peptide-polyester block copolymer where protease-mediated resorption is tuned through changing the chemistry of the base polymer backbone and protease specificity is imparted through incorporation of specific peptide sequences. Quartz crystal microbalance was used to quantify polymer surface resorption upon exposure to various enzymes. Aqueous solubility of the diacids and the thermal properties of the resulting polymer had a significant effect on enzyme-mediated polymer resorption. While peptide incorporation at 2 mol% had little effect on the final thermal and physical properties of the block copolymers, its incorporation improved polymer resorption significantly in a peptide sequence- and protease-specific manner. To our knowledge, this is the first example of a peptide-incorporated linear thermoplastic with protease-specific sensitivity reported in the literature. The product is a modular system for engineering specificity in how polyesters can resorb under physiological conditions, thus providing a potential framework for improving vascularization and integration of biomaterials used in tissue engineering.