In Vivo Regeneration of Large Bone Defects by Cross-Linked Porous Hydrogel: A Pilot Study in Mice Combining Micro Tomography, Histological Analyses, Raman Spectroscopy and Synchrotron Infrared Imaging
Tetsuya Adachi,
Francesco Boschetto,
Nao Miyamoto,
Toshiro Yamamoto,
Elia Marin,
Wenliang Zhu,
Narisato Kanamura,
Yoshiro Tahara,
Kazunari Akiyoshi,
Osam Mazda,
Ichiro Nishimura,
Giuseppe Pezzotti
Affiliations
Tetsuya Adachi
Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
Francesco Boschetto
Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
Nao Miyamoto
Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
Toshiro Yamamoto
Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
Elia Marin
Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
Wenliang Zhu
Ceramic Physics Laboratory, Kyoto Institute of Technology, Sakyo-ku, Matsugasaki, Kyoto 606-8585, Japan
Narisato Kanamura
Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
Yoshiro Tahara
Department of Chemical Engineering and Materials Science, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe-shi, Kyoto-fu 610-0394, Japan
Kazunari Akiyoshi
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Osam Mazda
Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, 465 Kajii-cho, Kyoto 602-8566, Japan
Ichiro Nishimura
Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, CA 90095, USA
Giuseppe Pezzotti
Ceramic Physics Laboratory, Kyoto Institute of Technology, Sakyo-ku, Matsugasaki, Kyoto 606-8585, Japan
The transplantation of engineered three-dimensional (3D) bone graft substitutes is a viable approach to the regeneration of severe bone defects. For large bone defects, an appropriate 3D scaffold may be necessary to support and stimulate bone regeneration, even when a sufficient number of cells and cell cytokines are available. In this study, we evaluated the in vivo performance of a nanogel tectonic 3D scaffold specifically developed for bone tissue engineering, referred to as nanogel cross-linked porous-freeze-dry (NanoCliP-FD) gel. Samples were characterized by a combination of micro-computed tomography scanning, Raman spectroscopy, histological analyses, and synchrotron radiation–based Fourier transform infrared spectroscopy. NanoCliP-FD gel is a modified version of a previously developed nanogel cross-linked porous (NanoCliP) gel and was designed to achieve highly improved functionality in bone mineralization. Spectroscopic imaging of the bone tissue grown in vivo upon application of NanoCliP-FD gel enables an evaluation of bone quality and can be employed to judge the feasibility of NanoCliP-FD gel scaffolding as a therapeutic modality for bone diseases associated with large bone defects.
