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

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Poly(glycerol sebacate) (PGS) is a biodegradable, elastomeric polymer that has been explored for applications including tissue engineering, 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 prolonged curing at high temperatures, 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 (5.5kDa) disks with 21% methacrylation lost 40.1 ± 11.8% of their mass over 11 weeks in vivo whereas 47% methacrylated disks lost just 14.3 ± 1.4% of their mass over the period. Daunorubicin release from PGS-M occurred in a linear fashion without a substantial initial burst. Further, increasing the degree of methacrylation extended the release of encapsulated drug. After 60 days, 21%, 27%, and 47% methacrylated disks with the same drug loading (w/w) released 56.8 ± 5.4%, 15.1 ± 0.4%, and 15.4 ± 0.3% of encapsulated drug, respectively. Importantly, the 27% and 47% methacrylated disks consistently released ~ 0.25% (w/w) of encapsulated drug per day with no burst release. Histological evaluation also suggested that PGS-M is biocompatible, eliciting limited inflammation and fibrous encapsulation when implanted subcutaneously. This report presents the first long-term in vitro studies and first in vivo studies using PGS-M and demonstrates the ability to tune PGS-M degradation rate, use PGS-M to encapsulate drug, and obtain sustained drug release over months.