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自组装多肽水凝胶 SPG-178-Gel 促进牙髓干细胞的骨再生和三维成骨诱导的疗效。

Efficacy of a Self-Assembling Peptide Hydrogel, SPG-178-Gel, for Bone Regeneration and Three-Dimensional Osteogenic Induction of Dental Pulp Stem Cells.

机构信息

1 Division of Medical-Dental Regenerative Medicine, Center for Advanced Oral Science, Graduate of Dentistry, Aichi Gakuin University , Nagoya, Japan .

2 Menicon Co., Ltd. , Nagoya, Japan .

出版信息

Tissue Eng Part A. 2017 Dec;23(23-24):1394-1402. doi: 10.1089/ten.TEA.2017.0025. Epub 2017 Jul 24.

DOI:10.1089/ten.TEA.2017.0025
PMID:28530133
Abstract

The aim of this study was to assess the efficacy of a self-assembling peptide hydrogel as a scaffold for bone regeneration. We used a neutral and injectable self-assembling peptide hydrogel, SPG-178-Gel. Bone defects (5 mm in diameter) in rat calvarial bones were filled with a mixture of alpha-modified Eagle's medium and peptide hydrogel. Three weeks after surgery, soft X-ray and microcomputed tomography (micro-CT) images of the gel-treated bones showed new bone formations in the periphery and in central areas of the defects. Next, we evaluated the three-dimensional osteogenic induction of dental pulp stem cells (DPSCs), a type of mesenchymal stem cell, in SPG-178-Gel. We first confirmed that the osteogenic differentiation of DPSCs was significantly promoted by osteogenic induction medium containing recombinant human bone morphogenetic protein-4 (rhBMP-4) in a two-dimensional cell culture. Then, we verified DPSC proliferation and osteogenic differentiation in a three-dimensional cell culture using SPG-178-Gel. The gene expression levels of osteopontin, osteocalcin, and collagen type I were significantly increased when DPSCs were cultured in SPG-178-Gel with the osteogenic induction medium. Micro-CT observations showed the formation of widespread calcium deposition. In conclusion, SPG-178-Gel was adequately effective as a scaffold and can be a suitable tool for bone formation in vivo and in vitro. These findings suggest that the self-assembling peptide hydrogel, SPG-178-Gel, could be a promising tool for bone tissue engineering.

摘要

本研究旨在评估自组装肽水凝胶作为骨再生支架的疗效。我们使用了中性可注射自组装肽水凝胶 SPG-178-Gel。在大鼠颅骨骨缺损(直径 5mm)中填充了α-改良的 Eagle 培养基和肽水凝胶的混合物。手术后 3 周,凝胶处理过的骨骼的软 X 射线和微计算机断层扫描(micro-CT)图像显示在缺陷的外围和中央区域有新骨形成。接下来,我们评估了牙髓干细胞(DPSCs)在 SPG-178-Gel 中的三维成骨诱导作用,DPSCs 是一种间充质干细胞。我们首先证实,在二维细胞培养中,含有重组人骨形态发生蛋白-4(rhBMP-4)的成骨诱导培养基可显著促进 DPSCs 的成骨分化。然后,我们使用 SPG-178-Gel 验证了三维细胞培养中 DPSCs 的增殖和成骨分化。当 DPSCs 在含有成骨诱导培养基的 SPG-178-Gel 中培养时,骨桥蛋白、骨钙素和 I 型胶原的基因表达水平显著增加。微 CT 观察显示广泛的钙沉积形成。总之,SPG-178-Gel 作为支架是足够有效的,可以作为体内和体外骨形成的合适工具。这些发现表明,自组装肽水凝胶 SPG-178-Gel 可能是骨组织工程的一种有前途的工具。

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