Methacrylated poly(glycerol sebacate) as a photocurable, biocompatible, and biodegradable polymer with tunable degradation and drug release kinetics

Abstract

Abstract Poly(glycerol sebacate) (PGS) is a biodegradable, elastomeric polymer that has been explored for applications ranging from tissue engineering to drug delivery and wound repair. Despite its promise, its biomedical utility is limited by its rapid, and largely fixed, degradation rate. Additionally, its preparation requires high temperatures for long periods of time, rendering it incompatible with heat-sensitive molecules, complex device geometries, and high-throughput production. In this study, we synthesized methacrylated PGS (PGS-M), imparting the ability to rapidly photocross-link the polymer. Increasing the degree of methacrylation was found to slow PGS-M degradation; PGS-M (5.5 kDa) disks with 21% methacrylation lost 43% of their mass over 11 weeks in vivo whereas 47% methacrylated disks lost just 14% of their mass over the same period. Increasing the methacrylation also extended the release of encapsulated daunorubicin by up to two orders of magnitude in vitro, releasing drug over months instead of one week. Like PGS, PGS-M exhibited good biocompatibility, eliciting limited inflammation and fibrous encapsulation when implanted subcutaneously. These studies are the first to perform long-term studies demonstrating the ability to tune PGS-M degradation rate, use PGS-M to release drug, demonstrate sustained release of drug from PGS-M, and evaluate PGS-M behavior in vivo. Taken together, these studies show that PGS-M offers several key advantages over PGS for drug delivery and tissue engineering, including rapid curing, facile loading of drugs without exposure to heat, tunable degradation rates, and tunable release kinetics, all while retaining the favorable biocompatibility of PGS.