Skull bone regeneration in nonhuman primates by controlled release of bone morphogenetic protein-2 from a biodegradable hydrogel.
The objective of this study was to investigate the feasibility of biodegradable gelatin hydrogels as the controlled-release carrier of bone morphogenetic protein-2 (BMP-2) to enhance bone regeneration at a skull defect of nonhuman primates. Hydrogels with 3 different water contents were prepared through glutaraldehyde crosslinking of gelatin with an isoelectric point of 9.0 under varied reaction conditions. A critical-sized defect (6 mm in diameter) was prepared at the skull bone of skeletally mature cynomolgus monkeys, and gelatin hydrogels incorporating various doses of BMP-2 were applied to the defects. When the bone regeneration was evaluated by soft radiography and bone mineral density (BMD) examinations, the gelatin hydrogel incorporating BMP-2 exhibited significantly higher osteoinduction activity than did an insoluble bone matrix that incorporated BMP-2 (one of the best osteoinduction systems), although the activity depended on the water content of hydrogels. BMD enhancement was highest for the gelatin hydrogel that had a water content of 97.8 wt% among all types of hydrogels. Moreover, the gelatin hydrogel enabled BMP-2 to induce the bone regeneration in nonhuman primates even at low doses. We conclude that the controlled release of BMP-2 for a certain time period was essential to inducing the osteoinductive potential of BMP-2.
Takahashi
Yoshitake
Y
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Yamamoto
Masaya
M
Yamada
Keisuke
K
Kawakami
Osamu
O
Tabata
Yasuhiko
Y
D020341:Absorbable Implants; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008252:Macaca fascicularis; D008297:Male; D011817:Rabbits; D012887:Skull Fractures / Q000188:drug therapy* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D016896:Treatment Outcome
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D016212:Transforming Growth Factor beta