Lipase-resistant poly(glycerol sebacate) via bulk physical entrapment of orlistat

Poly(glycerol sebacate) (PGS) has become one of the most promising new tissue engineering scaffold materials-of-construction. We hypothesized that the lipase inhibitor Orlistat might be suitable for inhibiting lipase-mediated PGS degradation. Here we investigated whether Orlistat can: (1) be physically transported into PGS using 70% (v/v) ethanol in water as a carrier, (2) be stably entrapped within the PGS bulk upon exchange of alcohol for water, and (3) inhibit PGS degradation by lipases. Control 5×5×0.25mm PGS scaffolds comprised of 50 μm struts and identical scaffolds loaded with Orlistat were challenged in vitro by a lipase solution (2000 U/ml). Scaffolds were incubated at 37°C for 1.5, 2, or 3 hours and then assessed by scanning electron microscopy. While evidence of control degradation was apparent after 1.5 h, little degradation was seen in the Orlistat-loaded scaffolds. By 3 hours, while Orlistat-loaded scaffolds began to exhibit modest degradation, controls had undergone rupture of structural elements. Of note, we observed that the path of lipase-mediated degradation was not homogeneous, but appeared to follow pre-existing imperfections in the PGS struts. Results will help guide the design of PGS scaffolds with controllable lipase-resistance.