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

交联多孔水凝胶在体内修复大骨缺损:一项结合微断层扫描、组织学分析、拉曼光谱和同步红外成像的小鼠初步研究

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作者:Tetsuya Adachi, Francesco Boschetto, Nao Miyamoto, Toshiro Yamamoto, Elia Marin, Wenliang Zhu, Narisato Kanamura, Yoshiro Tahara, Kazunari Akiyoshi, Osam Mazda, Ichiro Nishimura, Giuseppe Pezzotti

Abstract

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.

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