Cell-Mediated, Oxidatively Degradable Polyurethane/Ceramic Tissue Scaffolds for Bone and Articular Joint Repair

Abstract

Polyurethanes (PURs) are an attractive material for tissue engineering bone graft substitutes since they can be formulated to be injectable, settable, and biocompatible, and their mechanical properties and degradation rates can be tuned for specific orthopedic applications. Recently, a novel poly(thioketal urethane) (PTKUR) bone graft was developed to address unpredictable resorption associated with hydrolytic degradation of ester groups in poly(ester urethane) bone grafts in vivo. In this work, nanocrystalline hydroxyapatite (nHA) was incorporated with PTKUR to exploit the osteogenic and mechanical benefits of nHA in a polymeric nHA-PTKUR bone graft. nHA was grafted with lysine triisocyanate (LTI) to enhance nHA dispersion in a lysine-based nHA-PTKUR hybrid polymer that exhibits a complementary combination of cell-mediated resorption mechanisms. In this work, we examine the capacity for translation to a manufacturing setting and the feasibility of an FDA submission. This includes a preclinical study evaluating in vivo bone cement remodeling by both intramembranous and endochondral ossification characterized in a rabbit femoral condyle defect model.