Quantitative Measures of Osteoinductivity of a Porous Poly(propylene fumarate) Bone Graft Extender

Abstract

Bioresorbable bone graft substitutes could alleviate disadvantages associated with the use of autografts, allografts, and other synthetic materials. However, little is known about the minimum autograft/extender ratio for a given material at which a sufficient osteoinductive effect is still seen. Therefore, we investigated a bioresorbable bone graft substitute made from the unsaturated polyester poly(propylene fumarate), PPF, at various mixing ratios with autograft. The bone graft extender is cross-linked in the presence of a hydroxylapatite filler and effervescent foaming agents citric acid and sodium bicarbonate. The porous bone graft extender material develops porosity in vivo by generating carbon dioxide during the effervescent reaction, resulting in foam formation and expansion with respective pore sizes of 50 to 1000 μm. In an attempt to determine how much cancellous autograft bone could be extended with the poly(propylene fumarate) material and at which ratio the autograft/extender combination remained supportive of the overall structural integrity of the repairing defect site, we studied the amount of new bone formation on implantation of the materials in 3-mm holes made in the anteromedial tibial metaphysis of Sprague-Dawley rats. The extender formulation was analyzed at high autograft/extender (75% autograft/25% extender) and low autograft/extender (25% autograft/75% extender) mixing ratios and compared with negative (extender alone) and positive (autograft alone) controls. Animals from each of the formulations were killed in groups of eight at 6 weeks postoperatively. Hence, a total of 32 animals were included in this study. Histologic analysis of the healing process revealed enhanced in vivo osteoinduction with the bone graft extender regardless of the autograft loading. Histomorphometry did not show any statistically significant difference between the high and low autograft/extender ratios. All formulations maintained implant integrity and did not provoke sustained inflammatory responses. This study suggested that the presence of even a small amount of autograft within the polymer-based bone graft extender results in significant enhancement of osteoinduction. This finding has immediate applicability to the development of bone graft extender formulations for clinical use.