Synthesis of Cell-responsive, Biodegradable Polyureas for Ligament Tissue Engineering

Abstract

An estimated 200,000 injuries to the anterior cruciate ligament (ACL) occur annually in the United States, with approximately 100,000 total ACL reconstructions performed each year. Due to inherent limitations with existing ACL reconstruction strategies, the development of tissue engineered ligaments is a key area of musculoskeletal research. Although great strides have been made in the scaffold design, current strategies are limited by the inability to replicate the mechanical behavior of native ligament tissue with synthetic polyesters or natural polymers. Poly(ester urethane)s have recently been investigated as possible scaffold materials because of their established biocompatibility, excellent mechanical properties, and exceptionally tunable structure. However, non-specific degradation makes it difficult to tailor polyurethane structure to complement ligament regeneration. In contrast, a biomaterial that features system-responsive degradation would integrate with native ligament remodeling and thus provide effective load transfer to newly formed tissue that is necessary to restore mechanical integrity. In this study, enzyme-labile peptide sequences were conjugated to ether-based polyols to form collagen-mimetic soft segments that feature cell-responsive degradation. Synthetic routes were first developed to functionalize these polyols with favorable end groups for peptide coupling. Upon successful conjugation, biodegradable soft segments were then incorporated into the structure of linear polyurea elastomers. By varying soft segment chemistry, soft segment molecular weight, and the hard to soft segment ratio, a library of cell-responsive, biodegradable polyureas was developed. This library can then be used to elucidate key structure-property relationships necessary to complement neotissue formation. Overall, synthesis of a novel biomaterial that combines the strength and tunability of synthetic elastomers with cell-responsive degradation will assist in the development of an improved tissue engineered graft for ACL reconstruction.