In vivo Evaluation of a Novel Chitosan/ HAp Composite Biomaterial as a Carrier of rhBMP-2

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  • Kashiwazaki Haruhiko
    Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University
  • Yamaguchi Keisuke
    Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University
  • Harada Naoki
    Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University
  • Akazawa Toshiyuki
    Industrial Research Institute, Industrial Technology Research Development, Hokkaido Research Organization
  • Murata Masaru
    Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido
  • Iizuka Tadashi
    Support Section for Education and Research, Graduate School of Dental Medicine, Hokkaido University
  • Ikoma Toshiyuki
    Department of Inorganic Materials, Tokyo Institute of Technology
  • Tanaka Junzo
    Department of Inorganic Materials, Tokyo Institute of Technology
  • Inoue Nobuo
    Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University

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Abstract

We developed a porous chitosan/ hydroxyapatite (HAp) composite, in which the HAp nanocrystals align along the chitosan molecules, and examined the biocompatibility, osteoinductive activity, and the ability to act as a carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2) of this novel biomaterial. The composite was subcutaneously implanted into the backs of 11-week-old SD rats, with or without rhBMP-2 (5 μg). At 2 and 8 weeks after the implantation, the composite was explanted for morphohistological evaluation. In the presence of rhBMP-2, ectopic bone formation was found at 2 weeks and maturation of the newly formed bone around the composite at 8 weeks. Chitosan/HAp composite alone caused little inflammation, and new blood vessel growth and multinucleated giant cells were found around the composite, accompanied with roughening of the surface due to degradation at 2 weeks; however, neither cartilage nor bone formation was found around the composite. With rhBMP-2, the bioabsorption of the composite was accelerated as the rhBMP-2-induced bone matured. Histomorphometrical analysis showed that the mean value of the composite areas with rhBMP-2 was significantly smaller than that without rhBMT-2 at 2 and 8 weeks after the implantation. These results suggested that the novel chitosan/ HAp composite was an effective bioabsorbable material as a carrier of rhBMP-2.

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