Research Project
2644771
Our preliminary studies on biodegradable bone cements were conducted on formulations containing insoluble fillers such as hydroxyapatite. Although mechanical strength diminished on exposure to water, mass loss occurred slowly. These are nonporous cements and inhibit bone ingrowth due to their lack of porosity. A bone cement is proposed herein based on the in situ crosslinking of poly(propylene fumarate) with a vinyl monomer using soluble organic calcium salts (e.g., calcium gluconate) as fillers. The rapid leaching of the filler develops a porosity which facilitates both bone ingrowth and hydrolysis of the polymeric matrix. Thus it acts as an osteoconductive path. The cement will be formulated with a high PPF/monomer ratio which minimizes homopolymerization of the monomer. Viscosity is controlled by incorporation of a biocompatible oil (e.g., peanut oil) which minimizes loss of monomer during cure. Based on continued pilot studies, Phase I in vitro studies include measurement of compressive strength and modulus, porosity and microstructure, mass loss and dimensional stability. the feasibility of this approach will be the observation of bony ingrowth with simultaneous matrix erosion of implants in a rat tibial defect model. Biocompatibility will be judged by periodic histological examination of the implant site and surrounding tissue. To be considered in Phase II is the incorporation of a growth factor (e.g., bone morphogenic protein) into the cement enabling it to serve in an osteoinductive capacity. PROPOSED COMMERCIAL APPLICATION: Our resorbable osteoconductive grout will offer substantial advantages: (1) because we use a pre-polymerized and fully characterized biopolymer, which requires only cross-linking to go from a hand-moldable putty to bone-like hardness in minutes, there is no potential for volatilization of monomer: (2) our use of soluble calcium organic salts uniquely provided for osteoconduction commensurate with bone wound healing by "designing" the appropriate porosity directly into the cement; and (3) because of the low temperature rise in our system, our cement will also serve as a vehicle for a selected osteoinductive bone regenerating protein.
