ABSTRACT

Much research has been conducted on fabricating biomimetic biomaterials in vitro. Tissue engineering approaches are often conducted by combining cells, scaffolds, and growth factors. However, the degradation rate of scaffolds is difficult to control and the degradation byproducts occasionally limit tissue regeneration. To overcome these issues, we have developed a novel system using a thermo-responsive hydrogel that forms scaffold-free, three-dimensional (3D) cell constructs with arbitrary size and morphology. 3D cell constructs prepared using bone marrow-derived stromal stem cells (BMSCs) exhibited self-organizing ability and formed bone-like tissue with endochondral ossification. Endothelial cells were then introduced into the BMSC construct and a vessel-like structure was formed within the constructs. Additionally, the bone formation ability was promoted by endothelial cells and cell constructs could be freeze-dried to improve their clinical application. A pre-treatment with specific protein protectant allowed for the fabrication of novel bone substitutes composed only of cells. This 3D cell construct technology using thermo-responsive hydrogels was then applied to other cell species. Cell constructs composed of dental pulp stem cells were fabricated, and the resulting construct regenerated pulp-like tissue within a human pulpless tooth. In this review, we demonstrate the approaches for the in vitro fabrication of bone and dental pulp-like tissue using thermo-responsive hydrogels and their potential applications.

摘要

已经对体外制造仿生生物材料进行了大量研究。组织工程方法通常通过结合细胞、支架和生长因子来进行。然而，支架的降解速率难以控制，降解副产物有时会限制组织再生。为了克服这些问题，我们开发了一种使用热响应水凝胶的新型系统，该系统可形成具有任意尺寸和形态的无支架、三维 (3D) 细胞结构。使用骨髓来源的基质干细胞 (BMSC) 制备的 3D 细胞构建体表现出自组织能力并形成具有软骨内骨化的骨样组织。然后将内皮细胞引入 BMSC 构建体，并在构建体内形成血管样结构。此外，内皮细胞促进骨形成能力，细胞构建体可以冷冻干燥以改善其临床应用。用特定的蛋白质保护剂进行预处理可以制造仅由细胞组成的新型骨替代品。然后将这种使用热响应水凝胶的 3D 细胞构建技术应用于其他细胞种类。制造了由牙髓干细胞组成的细胞构建体，并且由此产生的构建体在人类无髓牙内再生了牙髓样组织。在这篇综述中，我们展示了使用热响应水凝胶体外制造骨和牙髓样组织的方法及其潜在应用。用特定的蛋白质保护剂进行预处理可以制造仅由细胞组成的新型骨替代品。然后将这种使用热响应水凝胶的 3D 细胞构建技术应用于其他细胞种类。制造了由牙髓干细胞组成的细胞构建体，并且由此产生的构建体在人类无髓牙内再生了牙髓样组织。在这篇综述中，我们展示了使用热响应水凝胶体外制造骨和牙髓样组织的方法及其潜在应用。用特定的蛋白质保护剂进行预处理可以制造仅由细胞组成的新型骨替代品。然后将这种使用热响应水凝胶的 3D 细胞构建技术应用于其他细胞种类。制造了由牙髓干细胞组成的细胞构建体，并且由此产生的构建体在人类无髓牙内再生了牙髓样组织。在这篇综述中，我们展示了使用热响应水凝胶体外制造骨和牙髓样组织的方法及其潜在应用。以及由此产生的构建体在人类无髓牙内再生了牙髓样组织。在这篇综述中，我们展示了使用热响应水凝胶体外制造骨和牙髓样组织的方法及其潜在应用。以及由此产生的构建体在人类无髓牙内再生了牙髓样组织。在这篇综述中，我们展示了使用热响应水凝胶体外制造骨和牙髓样组织的方法及其潜在应用。