Bone regeneration using a bone morphogenetic protein-2 saturated slow-release gelatin hydrogel sheet: Evaluation in a canine orbital floor fracture model

Shinichi Asamura, Yuichi Mochizuki, Masaya Yamamoto, Yasuhiko Tabata, Noritaka Isogai

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Bone regeneration methods using bone inductive cytokines show promise, however, due to early diffusion and absorption of single applications of these cytokines, the bone inductive effects are limited. In this study, such a system was applied, using gelatin hydrogel as a carrier to slowly release (bone morphogenetic proteins) BMP-2 over a relatively long period in vivo. By coupling this slow-release system with a biodegradable copolymer, this composite was evaluated by grafting into bone defect sites of a canine orbital floor fracture model. Radio-iodinated BMP-2 incorporated into the gelatin hydrogel carrier and subcutaneously implanted into nude mice showed a similar slow release (approximately, 60% at 3 days and 80% at 14 days) as the radiolabeled hydrogel carrier alone. In contrast, greater than 90% of fluid-injected BMP-2 was lost in the injection site within the first 8 hours. Using a dog model of orbital floor fracture, a complex of BMP-2-saturated gelatin hydrogel and a polylactide-based biodegradable copolymer was implanted into the orbital bone defect. Bone structural analysis, using radiography, histologic examination, and microfocus CT, showed greatly enhanced new bone formation and defect healing at 5 weeks in comparison to implanted biodegradable copolymer directly saturated with the same amount of BMP-2 (no slow-release hydrogel carrier). A trabecular structure resembling that normal bone tissue was restored in the new bone tissue generated by the slow-release constructs. Thus study demonstrates the potential of slow-release BMP-2 for bone healing of difficult defects.

Original languageEnglish
Pages (from-to)496-502
Number of pages7
JournalAnnals of Plastic Surgery
Volume64
Issue number4
DOIs
Publication statusPublished - 2010 Apr 1
Externally publishedYes

Keywords

  • BMP-2
  • Biodegradable polymer
  • Bone structural analysis
  • Gelatin hydrogel
  • Orbital floor fracture

ASJC Scopus subject areas

  • Surgery

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