Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein

Masaya Yamamoto, Yoshitake Takahashi, Yasuhiko Tabata

Research output: Contribution to journalArticlepeer-review

305 Citations (Scopus)


The objective of this study is to develop a carrier for the controlled release of bone morphogenetic protein-2 (BMP-2) suitable for enhancement of the bone regeneration activity. Hydrogels with different water contents were prepared through glutaraldehyde crosslinking of gelatin with an isoelectric point of 9.0 under varied reaction conditions. Following subcutaneous implantation of the gelatin hydrogels incorporating 125I-labeled BMP-2 into the back of mice, the in vivo retention period of BMP-2 prolonged with a decrease in the water content of hydrogels used, although every time period was much longer than that of BMP-2 solution injection. Ectopic bone formation studies demonstrated that the alkaline phosphatase (ALP) activity and osteocalcin content around the implanted site of BMP-2-incorporated gelatin hydrogels were significantly high compared with those around the injected site of BMP-2 solution. The values became maximum for the gelatin hydrogel incorporating BMP-2 with a middle period of BMP-2 retention, while bone formation was histologically observed around the hydrogel incorporating BMP-2. The ALP activity was significantly higher than that of the collagen sponge incorporating BMP-2. We concluded that the controlled release technology of BMP-2 for a certain time period was essential to induce the potential activity for bone formation.

Original languageEnglish
Pages (from-to)4375-4383
Number of pages9
Issue number24
Publication statusPublished - 2003 Nov


  • Biodegradable gelatin hydrogel
  • Bone morphogenetic protein
  • Controlled release
  • Ectopic bone formation


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