Allograft mineralized bone particle/polyurethane composites for bone tissue engineering

Abstract

Healing of bone defects such as open fractures is a challenging clinical problem. An ideal treatment for bone defects would restore both form and function of the tissue. In this research, a two-component allograft bone particle/polyurethane system that can be compression molded or injected to treat bone defects has been developed. This biodegradable polyurethane (PUR) consists of lysine triisocyanate (LTI), polyester polyol, triethyldiamine (TEDA) catalyst, and allograft mineralized bone particles (AMBP). AMBP, which is bound to the PUR phase, is used as a filler to enhance mechanical properties and provide a resorbable pathway for cellular infiltration. Furthermore, pores can be incorporated in this system with the addition of water that reacts with isocyante groups, yielding carbon dioxide which functions as a blowing agent. For weight-bearing implant applications, non-porous composites have been fabricated by reactive compression molding. At volume fractions exceeding the random close-packing (RCP) limit, the particulated allograft component presented a nearly continuous osteoconductive pathway for cells. Furthermore, an injectable AMBP/PUR composite has been developed as a bone void filler (BVF) with tunable properties that supports rapid cellular infiltration and remodeling. The materials incorporate particulated allograft bone particles and have variable (e.g., 30 - 70%) porosities. When injected in femoral plug defects in athymic rats, the composites supported extensive cellular infiltration, allograft resorption, and new bone formation at three weeks. As a drug delivery system, recombinant human morphogenetic protein (rhBMP-2) was added prior to injection of the AMBP/PUR BVF. AMBP/PUR BVF with the incorporation of rhBMP-2 showed substantial new bone formation in a 15 mm NZW rabbit calvaria critical-size defect. Finally, an injectable AMBP/PUR putty (< 5% porosity) with the incorporation of rhBMP-2 was synthesized and studied in the rabbit distal femur model. Substantial bone remodeling was observed at rhBMP-2 levels less than standard dose, suggesting an efficient release of rhBMP-2. Results from this research suggest that both the AMBP/PUR composites are a promising, versatile biomaterial for bone regeneration in orthopaedic and craniofacial applications.