Bone regeneration by transforming growth factor beta1 released from a biodegradable hydrogel.
This paper describes the sustained release of transforming growth factor beta1 (TGF-beta1) from a biodegradable hydrogel based on polyion complexation for the enhancement of bone regeneration activity. Basic TGF-beta1 was adsorbed onto the biodegradable hydrogel of acidic gelatin with an isoelectric point of 5.0 by an electrostatic interaction. The TGF-beta1 could not be adsorbed onto basic gelatin. When acidic gelatin hydrogels incorporating 125I-labeled TGF-beta1 were implanted into the back subcutis of mice, the radioactivity decreased with time and the in vivo retention of TGF-beta1 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-beta1 correlated well with that of gelatin hydrogels, indicating that TGF-beta1 was released from the gelatin hydrogel as a result of hydrogel biodegradation. The ability of TGF-beta1-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-beta1. This indicates that the sustained release of TGF-beta1 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-beta1 which is too short to induce bone regeneration. It is possible that the slow degradation of the hydrogel physically blocked TGF-beta1-induced bone regeneration at the skull defect. It can be concluded that the gelatin hydrogel is a promising matrix of TGF-beta1 release to induce skull bone regeneration.
Yamamoto
M
M
Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto, Japan.
Tabata
Y
Y
Hong
L
L
Miyamoto
S
S
Hashimoto
N
N
Ikada
Y
Y
D020341:Absorbable Implants; D000287:Administration, Topical; D000818:Animals; D001673:Biodegradation, Environmental; D001861:Bone Regeneration / Q000187:drug effects*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005260:Female; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D051379:Mice; D010084:Oxidation-Reduction; D011817:Rabbits; D011994:Recombinant Proteins; D012886:Skull / Q000187:drug effects* / Q000473:pathology; D055672:Static Electricity; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D014867:Water / Q000378:metabolism
D003692:Delayed-Action Preparations; D020100:Hydrogels; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014867:Water; D005780:Gelatin