SBIR-STTR Award

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.

Thesaurus Terms:
biomaterial development /preparation, calcium, orthopedics, physiologic bone resorption, polymer, vegetable oil bioengineering /biomedical engineering, biomaterial compatibility, biomaterial evaluation, bone prosthesis, gluconate histology, laboratory ratNATIONAL INSTITUTE OF DENTAL RESEARCH

Trauma, oncologic surgery, and congenital disorders often leave patients with large bony defects that require reconstruction. Autografts and allografts are used in current bone graft procedures to repair defects. However, each has clinical drawbacks. The proposed bioresorbable bone graft substitute is made from the unsaturated polyester, poly(propylene glycol-co-fumaric acid), which can be cross-linked in the presence of soluble and insoluble calcium filler salts and grouted directly into a bony void. This graft substitute provides an osteoconductive pathway for bone ingrowth. In Phase I the technical objective was to demonstrate the feasibility of a degradable grout to encourage bony ingrowth and void filling by the use of soluble fillers. Following this demonstration of a relationship between salt-promoted porosity of the bone graft substitute and cell ingrowth in Phase I, the investigators now propose in Phase II the in vivo evaluation of grouts which encourage optimal ingrowth of bone cells and organized deposition of new bone. It is projected that the work will result in a grout formulation using a mixture of calcium salts that will leach from the graft substitute at a rate supportive of the overall structural integrity of the repairing site, while optimum rates of bone ingrowth and polymer degradation are maintained. PROPOSED COMMERCIAL APPLICATION: There are over 450,000 bone graft procedures annually in the U.S. (2.2 million worldwide) with a market potential of $400 to $600 million. The approved synthetic grafts are considered to be inferior to the use of autograft or allograft materials. Bioresorbable bone void fillers could provide a viable alternative to autografts and allografts used in current bone graft procedures to repair defects caused by surgery, tumors, trauma, implant revisions and infecctions and also for joint fusion.