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

doi:10.3390/ma13194275

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.

Highlights

People frequently suffer from bone diseases associated with bone defects as a consequence of bone resorption and inactivation of the natural processes of bone remodeling [1]
NanoCliP-FD scaffold into the bone defect (Figure 1b)
Micrograph and SR-FTIR maps were obtained from a Several types of 3D scaffolds for bone tissue engineering have been reported in the literature [18,19], including hydroxyapatite bioceramics [20], collagen, atelocollagen, chitosan and alginate [21,22,23], polyethylene glycol [24], hydrogels [25,26], and other materials, such as carbon nanotubes [26,27]

Summary

Introduction

People frequently suffer from bone diseases associated with bone defects as a consequence of bone resorption and inactivation of the natural processes of bone remodeling [1]. In patients receiving biological medicine treatment, osteomyelitis sometimes results in osteonecrosis, especially in the jaw, which is known as medication-related osteonecrosis of the jaw (MRONJ) [2]. Periodontal diseases may cause tooth loss and alveolar bone defects that eventually lead to systemic infection, eating disorders, malnutrition, and dementia [3,4]. Large bone defects can be a consequence of the surgical removal of bone tumors. All of these diseases seriously reduce patient quality of life (QOL) and activities of daily living (ADLs). It is important to counteract bone loss with the preventive preparation of sufficient bone tissue for transplantation—this remains the most critical step involved in bone regeneration surgery

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Discussion

Conclusion