Bone regeneration by transforming growth factor β1 released from a biodegradable hydrogel

This paper describes the sustained release of transforming growth factor beta 1 (TGF-beta 1) from a biodegradable hydrogel based on polyion complexation for the enhancement of bone regeneration activity. Basic TGF-beta 1 was adsorbed onto the biodegradable hydrogel of acidic gelatin with an isoelectric point of 5.0 by an electrostatic interaction. The TGF-beta 1 could not be adsorbed onto basic gelatin. When acidic gelatin hydrogels incorporating I-125-labeled TGF-beta 1 were implanted into the back subcutis of mice, the radioactivity decreased with time and the in vivo retention of TGF-beta 1 was prolonged with a decrease in the water content of hydrogels. The higher the water content of hydrogels, the faster their biodegradation. The in vivo retention of TGF-beta 1 correlated well with that of gelatin hydrogels, indicating that TGF-beta 1 was released from the gelatin hydrogel as a result of hydrogel biodegradation. The ability of TGF-beta 1-incorporated into acidic gelatin hydrogels to induce bone regeneration was evaluated in a rabbit calvarial defect model. Eight weeks after treatment, the gelatin hydrogels with water contents of 90 and 95 wt% induced significantly high bone regeneration compared with those with lower and higher water contents and free TGF-beta 1. This indicates that the sustained release of TGF-beta 1 from the hydrogel with suitable in vivo degradability is necessary to effectively enhance its osteoinductive function. Rapid hydrogel degradation will result in a retention time of TGF-beta 1 which is too short to induce bone regeneration. It is possible that the slow degradation of the hydrogel physically blocked TGF-beta 1-induced bone regeneration at the skull defect. It can be concluded that the gelatin hydrogel is a promising matrix of TGF-beta 1 release to induce skull bone regeneration. (C) 2000 Elsevier Science B.V. All rights reserved.