Promoted bone healing at a rabbit skull gap between autologous bone fragment and the surrounding intact bone with biodegradable microspheres containing transforming growth factor-beta 1

This study is a trial to promote repairing of the rabbit skull bone gap bet ween an autologous bone flap and the intact bone with biodegradable gelatin microspheres containing transforming growth factor-beta 1 (TGF-beta 1). A 10-mm diameter bone defect was prepared in rabbit skulls by drilling out a bone flap of 6 mm in diameter. After a surrounding gap defect of 2 mm was c reated and treated with 0.5 mu g of free TGF-beta 1 and gelatin microsphere s containing 0.5 mu g of free TGF-beta 1, the circular autologous bone flap was placed in the center. Significant bone healing at the gap defect was o bserved 3 weeks after implantation of the TGF-beta 1-containing gelatin mic rospheres. The bone mineral density (BMD) was significantly higher than tha t of other experimental groups. On the contrary, when applied with free TGF -beta 1, a fibrous tissue initially infiltrated into the gap defect, result ing in impairing bone healing. The tissue response was similar to that at t he defect implanted with empty gelatin microspheres and TGF-beta 1-free pho sphate-buffered saline solution alone. There was more space in the gap-fill ing bone in the 16-week view than the 3-week view. It is possible that this was an intermediate step along the way toward normal healing and formation of cancellous bone. We conclude that gelatin microspheres containing TGF-b eta 1 show promise as an agent to promote bone regeneration of subcritical size defects between surgically positioned autologous bone flaps and surrou nding host bone.