Platelet-derived growth factor enhancement of two alloplastic bone matrices

Background: The use of alloplastic matrices that mimic the mineral phase of bone has become a viable alternative to current mainstream therapies in dentistry such as allografts and autogenous grafts. Because alloplastic bone substitutes generally have relatively poor osteogenic properties, analyzing their potential as vehicles to deliver growth factors is an important step in assessing methods to enhance their clinical efficacy. The aim of these studies was to treat beta-tricalcium phosphate (beta-TCP) and calcium sulfate (CaSO4) with platelet-derived growth factor (PDGF)-BB to enhance the osteogenic capabilities of these materials. Methods: In the beta-TCP studies, PDGF-BB adsorption and release were accomplished using 1251 radiolabeled growth factor and non-radioactive human recombinant PDGF at a ratio of 1:300M. For the adsorption studies, the radiolabeled PDGF-BB/ non-radioactive PDGF solutions with resultant PDGF concentrations of 10(-7) and 10(-8) M were incubated with beta-TCP from 1 to 120 minutes, and the amount of adsorbed I-125-PDGF-BB was measured using a gamma counter. Similar adsorption studies were conducted with a 30-minute incubation of beta-TCP with various PDGF concentrations. In vitro release studies were conducted with beta-TCP to which radiolabeled PDGF had been adsorbed as above. Release studies were also conducted with CaSO4 that was hydrated with the radioactive PDGF solution described above for the TCP studies. In vivo PDGF-BB release from beta-TCP and CaSO4 was evaluated in a mouse model, where the radioactive PDGF/nonradioactive PDGF-BB treated beta-TCP or CaSO4 sample was inserted subcutaneously and later removed for radioactive measurement. Proliferation of human osteoblastic cells in the presence of PDGF- treated beta-TCP or CaSO4 was assessed by H-3 thymidine incorporation. Results: The absorption studies revealed that PDGF-BB was absorbed in a concentration and time-dependent manner to beta-TCP. In the in vitro release studies, similar to 45% of the adsorbed PDGF-BB was released after 10 days. In vivo release from both materials occurred faster than in vitro release. Osteoblastic cells incubated with PDGF-BB-treated matrices showed significantly (P < 0.05, ANOVA) greater proliferation than with control matrices alone. Conclusion: These experiments demonstrate the feasibility of using PDGF-BB in combination with alloplastic materials such as beta-TCP or CaSO4 to serve as more effective bone graft materials with enhanced osteogenic properties.