Elastomeric high-mineral content hydrogel-hydroxyapatite composites for orthopedic applications

Abstract

The design of synthetic bone grafts that mimic the structure and composition of bone and possess good surgical handling characteristics remains a major challenge. We report the development of poly(2-hydroxyethyl methacry- late) (pHEMA)-hydroxyapatite (HA) composites termed "FlexBone" that possess osteoconductive mineral content approximating that of human bone yet exhibit elastomeric properties enabling the press-fitting into a defect site. The approach involves crosslinking pHEMA hydrogel in the presence of HA using viscous ethylene glycol as a solvent. The composites exhibit excellent structural integration between the apatite mineral component and the hydroxy- lated hydrogel matrix. The stiffness of the composite and the ability to withstand compressive stress correlate with the microstructure and content of the mineral component. The incorporation of porous aggregates of HA nanocrystals rather than compact micrometer-sized calcined HA effectively improved the resistance of the composite to crack propagation under compression. Freeze-dried FlexBone con-taining 50 wt % porous HA nanocrystals could withstand hundreds-of-megapascals compressive stress and <80% compressive strain without exhibiting brittle fractures. Upon equilibration with water, FlexBone retained good structural integration and withstood repetitive moderate (megapascals) compressive stress at body temperature. When subcutane- ously implanted in rats, FlexBone supported osteoblastic differentiation of the bone marrow stromal cells pre-seeded on FlexBone. Taken together, the combination of high osteocon- ductive mineral content, excellent organic-inorganic structural integration, elasticity, and the ability to support osteoblastic differentiation in vivo makes FlexBone a promising candidate for orthopedic applications. © 2008 Wiley Periodicals, Inc.