Nanogel tectonic porous 3D scaffold for direct reprogramming fibroblasts into osteoblasts and bone regeneration.

Nanogel tectonic porous 3D scaffold for direct reprogramming fibroblasts into osteoblasts and bone regeneration.
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DOI:
10.1038/s41598-018-33892-z
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发表时间:
2018-10-25
期刊:
影响因子:
4.6
通讯作者:
Mazda O
Mazda O
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sato Y;Yamamoto K;Horiguchi S;Tahara Y;Nakai K;Kotani SI;Oseko F;Pezzotti G;Yamamoto T;Kishida T;Kanamura N;Akiyoshi K;Mazda O

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工程化三维(3D)骨组织移植可为各种骨疾病患者提供治疗益处。为了实现这一目标,需要合适的3D支架和细胞。在本研究中,我们设计了一种用于人工三维支架的新型纳米凝胶结构材料,即纳米凝胶-交联孔(NanoCliP)-冻干(FD)凝胶,并评估了其作为骨组织工程三维支架的潜力。作为成骨细胞,直接转化的成骨细胞(DOBS)被使用,因为可以从患者的成纤维细胞中诱导出大量高功能的成骨细胞,这种方法可以通过微创的方法进行。NanoCliP-FD凝胶具有高度的渗透性,凝胶表面的纤维连接蛋白涂层使细胞能够有效地黏附,培养7d后细胞几乎占据了孔壁的全部表面。成骨细胞大量产生钙化的骨基质,培养至少可持续28天。含有DOBS的NanoCliP-FD凝胶在移植到人工制造的小鼠骨缺损处后,显著促进了体内的骨再生。本研究结果提示,NanoCliP-FD凝胶与DOBS的结合可能为骨疾病提供一种可行的治疗方式。
Transplantation of engineered three-dimensional (3D) bone tissue may provide therapeutic benefits to patients with various bone diseases. To achieve this goal, appropriate 3D scaffolds and cells are required. In the present study, we devised a novel nanogel tectonic material for artificial 3D scaffold, namely the nanogel-cross-linked porous (NanoCliP)-freeze-dried (FD) gel, and estimated its potential as a 3D scaffold for bone tissue engineering. As the osteoblasts, directly converted osteoblasts (dOBs) were used, because a large number of highly functional osteoblasts could be induced from fibroblasts that can be collected from patients with a minimally invasive procedure. The NanoCliP-FD gel was highly porous, and fibronectin coating of the gel allowed efficient adhesion of the dOBs, so that the cells occupied the almost entire surface of the walls of the pores after culturing for 7 days. The dOBs massively produced calcified bone matrix, and the culture could be continued for at least 28 days. The NanoCliP-FD gel with dOBs remarkably promoted bone regeneration in vivo after having been grafted to bone defect lesions that were artificially created in mice. The present findings suggest that the combination of the NanoCliP-FD gel and dOBs may provide a feasible therapeutic modality for bone diseases.
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