Synergistic effect of gelatin microspheres incorporating TGF-beta1 and a physical barrier for fibrous tissue infiltration on skull bone formation

The objective of this study is to examine whether or not bone formation at a skull bone defect induced by gelatin microspheres incorporating transforming growth factor (TGF)-beta1 is promoted by prevention of fibrous tissues into the defect. The 6-mm diameter bone defect of rabbit skulls was applied with gelatin microspheres incorporating TGF-beta1 or free TGF-beta1 and physically covered by a barrier membrane. When the bone formation at the defect was assessed 6 weeks postoperatively, combinational application of gelatin microspheres incorporating 0.1 microg of TGF-beta1 with the barrier membrane induced bone formation at the skull defect, in marked contrast to that of 0.1 microg of free TGF-beta1 and empty gelatin microspheres. Complete defect closure was histologically observed by the newly formed bone tissue. Without the barrier membrane, gelatin microspheres incorporating TGF-beta1 were less effective in inducing bone formation, whereas free TGF-beta1 and empty gelatin microspheres were ineffective. The skull defect was occupied by fibrous tissue infiltrated in place of bone tissue. The bone mineral density at the skull defect applied with gelatin microspheres incorporating TGF-beta1 plus the membrane was significantly higher than that of gelatin microspheres incorporating TGF-beta1 alone. The present data indicated that physical protection from the soft tissue infiltration enabled gelatin microspheres incorporating TGF-beta1 to synergistically enhance the osteoinductive ability at the skull defect.