Research Project
6787514
DESCRIPTION (provided by applicant): Spinal fusion is the most common type of bone grafting procedure. Despite the continuing evolution of devices designed to aid in interbody fusion, nonunion remains problematic. Stability of vertebral segments relies on solid bony fusion across the fusion site. In a typical process, autologous bone, the "gold standard," is used to construct the fusion site. However, the sometimes limited supply of autograft and concerns over the safety of allograft have fueled the search for synthetics. It is the hypothesis of this grant application that a biopolymeric scaffold can add dimensional stability to autograft bone while maintaining the osteoinductive properties of the autograft and supporting the volume and shape of the fusion site. The proposed bone graft substitute is based on the biodegradable polymer poly(propylene fumarate-co-fumaric acid), "PPF." PPF, an unsaturated polyester, can be crosslinked in the presence of effervescent and osteoconductive fillers and cured in situ yielding a porous bone-like scaffold in intimate contact with host tissue. The use of a degradable biopolymeric scaffold could, at least, extend the working volume of autograft without compromising its osteoconductive properties and, at best, improve upon the mechanical and bioactive properties of the grafl material as graft consolidation occurs. This Phase I study will determine if it is feasible to develop a PPF biopolymeric-based bone graft substitute suitable for the support of spinal fusion with feasibility defined as mechanics appropriate for immediate stabilization at placement and then continuing stabilization of the polymer-bone construct over the course of the fusion process concomitant with the maintenance of a porosity permissive for cellular ingrowth PPF-based test materials will be evaluated in vitro based upon these initial and temporal morphological and mechanical outcomes in both static and dynamic modes. The formulation that best meets these Phase I in vitro outcomes will be evaluated in vivo in Phase II to evaluate osteointegration and stability using biomechanical histological, and histomorphometric techniques.
