A pH-Triggered, Self-Assembled, and Bioprintable Hybrid Hydrogel Scaffold for Mesenchymal Stem Cell Based Bone Tissue Engineering.
A pH-Triggered, Self-Assembled, and Bioprintable Hybrid Hydrogel Scaffold for Mesenchymal Stem Cell Based Bone Tissue Engineering.
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一种 pH 触发、自组装、可生物打印的混合水凝胶支架，用于基于间充质干细胞的骨组织工程。
DOI：
10.1021/acsami.8b19094
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Che
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文献类型：
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作者：
Zhao Chen;Qazvini Nader Taheri;Sadati Monirosadat;Zeng Zongyue;Huang Shifeng;De La Lastra Ana Losada;Zhang Linghuan;Feng Yixiao;Liu Wei;Huang Bo;Zhang Bo;Dai Zhengyu;Shen Yi;Wang Xi;Luo Wenping;Liu Bo;Lei Yan;Ye Zhenyu;Zhao Ling;Cao Daigui;Yang Lijuan;Che
有效的骨组织工程可以恢复因创伤和/或某些疾病而受损的骨和骨骼功能。骨是一种复杂的组织，通过细胞、生物力学力和生物因子之间的协调相互作用来发挥功能。为了确定有效的间充质干细胞（MSC）为基础的骨组织再生的理想支架材料，在这里，我们开发和表征复合纳米水凝胶结合羧甲基壳聚糖（CMCh）和无定形磷酸钙（ACP）（指定为CMCh-ACP水凝胶）。我们证明了CMCh-ACP水凝胶可以通过将β-δ-内酯（GDL）掺入到水性分散体中或以pH触发的受控组装方式再水化酸性冻干纳米颗粒来容易地制备。CMCh-ACP水凝胶具有优异的生物相容性，并有效地支持MSC增殖和细胞粘附。此外，在增强BMP 9诱导的成骨分化的同时，CMCh-ACP水凝胶本身具有骨诱导性，并在体外诱导MSC中成骨细胞调节因子和骨标记物的表达。CMCh-ACP支架在体内显著增强BMP 9诱导的骨形成的效率和成熟度，同时抑制长期异位成骨中发生的骨吸收。因此，这些结果表明，pH响应性自组装CMCh-ACP可注射和生物打印水凝胶可以进一步开发作为一种新的支架骨祖细胞为基础的骨组织再生。
Effective bone tissue engineering can restore bone and skeletal functions that are impaired by traumas and/or certain medical conditions. Bone is a complex tissue and functions through orchestrated interactions between cells, biomechanical forces, and biofactors. To identify ideal scaffold materials for effective mesenchymal stem cell (MSC)-based bone tissue regeneration, here we develop and characterize a composite nanoparticle hydrogel by combining carboxymethyl chitosan (CMCh) and amorphous calcium phosphate (ACP) (designated as CMCh-ACP hydrogel). We demonstrate that the CMCh-ACP hydrogel is readily prepared by incorporating glucono δ-lactone (GDL) into an aqueous dispersion or rehydrating the acidic freeze-dried nanoparticles in a pH-triggered controlled-assembly fashion. The CMCh-ACP hydrogel exhibits excellent biocompatibility and effectively supports MSC proliferation and cell adhesion. Moreover, while augmenting BMP9-induced osteogenic differentiation, the CMCh-ACP hydrogel itself is osteoinductive and induces the expression of osteoblastic regulators and bone markers in MSCs in vitro. The CMCh-ACP scaffold markedly enhances the efficiency and maturity of BMP9-induced bone formation in vivo, while suppressing bone resorption occurred in long-term ectopic osteogenesis. Thus, these results suggest that the pH-responsive self-assembled CMCh-ACP injectable and bioprintable hydrogel may be further exploited as a novel scaffold for osteoprogenitor-cell-based bone tissue regeneration.