Nano Biomedicine
Calcified Honeycomb-shaped Collagen Maintains its Geometry in Vivo and Effectively Induces Vasculature and Osteogenesis

Yoshinori KUBOKI1, 2, 3, Shouhei IKU2, 3, Ryota YOSHIMOTO4, Tohru KAKU4, Hiroko TAKITA5, Dong LI6, Yasuo KOKAI6, Shunji YUNOKI7, Rachel L. SAMMONS8, Kazuhide OZEKI9, and Teruo MIYATA2

1Professor Emeritus, Hokkaido University, Sapporo, Japan
2Koken Institute, Koken Co., Ltd., Tokyo, Japan
3School of Medicine, Xinxiang Medical University, China
4School of Dentistry, Health Science University of Hokkaido, Hokkaido, Japan
5Graduate 5School Dental Medicine, Hokkaido University, Sapporo, Japan
6School of Medicine, Sapporo Medical University, Sapporo, Japan
7Tokyo Metropolitan Industrial Technology Research Institute, Tokyo, Japan
8School of Dentistry, Birmingham University, UK
9School of Mechanical Engineering, Ibaraki University, Hitachi, Japan

Nano Biomedicine 2009;1(2): 85-94, (Dec 30)

Honeycomb collagen (HC) with its unique geometric structure has been used in cell culture experiments to study the three-dimensional (3D) effects of the artificial matrix. When implanted in animal tissue however, HC was easily distorted and its geometric structure crushed. In order to elucidate the effect of 3D geometry of this scaffold in both in vitro and in vivo, we attempted to give it rigidity by calcifying and coating HC with hydroxyapatite. By using a calcifying solution with a high calcium (15 mM) and phosphate (9 mM) concentration, hydroxyapatite was evenly precipitated on the surface of HC, obtaining 10 times higher weight than the original HC. A mechanical strength test of the calcified HC showed a 4 times higher compression modulus than the original HC. Implantation of calcified HC into rats subcutaneously with BMP effectively induced bone, comparable with the HC and another conventional scaffold. Moreover, implantation of calcified HC without BMP induced vasculature along individual tunnels of the calcified HC, while the implantation of HC alone without BMP led to the degradation of the scaffold at 4-8 weeks.

Key words: honeycomb collagen, calcification, rigidity, vasculature, osteogenesis

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