Synthesis of a Porous, Biocompatible Tissue Engineering Scaffold Selectively Degraded by Cell-Generated Reactive Oxygen Species
Martin, John Robert
Biodegradable tissue engineering scaffolds are commonly fabricated from poly(lactide-co-glycolide) (PLGA) or similar polyesters that degrade by hydrolysis. PLGA hydrolysis generates acidic byproducts that trigger an accelerated, autocatalytic degradation mechanism that can create mismatched rates of biomaterial breakdown and tissue formation. Reactive oxygen species (ROS) are naturally produced by cells, and induction of inflammation and ROS is an inevitable in vivo response to biomaterial implantation. Thus, polymeric biomaterials that are selectively degraded by cell-generated ROS may have potential for creating scaffolds with better-matched rates of tissue in-growth and cell-mediated scaffold biodegradation. To explore this approach, a series of novel poly(thioketal) (PTK) urethane (PTK-UR) biomaterial scaffolds that degrade specifically by an ROS-dependent mechanism were synthesized. Unlike poly(ester-urethane) (PEUR) scaffolds, the PTK-UR scaffolds were stable under aqueous conditions out to 25 weeks but were selectively degraded by ROS. The in vitro oxidative degradation rates of the PTK-URs followed first-order degradation kinetics, were significantly dependent on PTK composition (p<0.05), and displayed dose-dependence with respect to ROS levels. In subcutaneous rat wounds, PTK-UR scaffolds supported cellular infiltration and granulation tissue formation, followed first-order degradation kinetics over 7 weeks, and produced significantly greater stenting of subcutaneous wounds compared to PEUR scaffolds. These combined results indicate that PTK-UR tissue engineering scaffolds have significant advantages over analogous polyester-based biomaterials and provide a robust, cell-degradable substrate for guiding new tissue formation.