Design of an osteoinductive biodegradable cell scaffold based on controlled release technology of bone morphogenetic protein

Biodegradable gelatin sponges with or without 50 wt% of β-tricalcium phosphate (β-TCP) incorporation were fabricated to design an osteoinductive scaffold that is capable of the controlled release of bone morphogenetic protein (BMP)-2. The sponges prepared had an interconnected pore structure with an average pore size of 200 μm, irrespective of the β-TCP incorporation. When seeded into the sponge by an agitated method, mesenchymal stem cells (MSC) isolated from rat bone marrow were homogeneously distributed throughout the sponge. Osteogenic differentiation experiments demonstrated that the in vitro differentiation and proliferation of MSC was enhanced by β-TCP incorporation. The in vivo osteoinduction activity of gelatin or β-TCP-incorporated gelatin sponges containing BMP-2 was studied in terms of histological and biochemical examinations following the implantation into the back subcutis of rats. As a result, homogeneous bone formation was histologically observed inside the sponge implanted, although the gelatin sponge exhibited significantly higher osteoinduction activity than that of the gelatin sponge incorporating β-TCP. The in vivo release test revealed that BMP-2 was released from the sponge in vivo, in a similar time period, whether or not β-TCP was incorporated. BMP-2 was retained for a time period longer than 28 days. These results suggest that the gelatin sponge with an ability to release BMP-2 is a promising cell scaffold for osteoinduction in vivo, although the effect of β-TCP incorporation on the osteoinductivity of sponges was different between the in vitro and in vivo systems.