Electrospun thermosensitive hydrogel scaffold for enhanced chondrogenesis of human mesenchymal stem cells
Electrospun thermosensitive hydrogel scaffold for enhanced chondrogenesis of human mesenchymal stem cells
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DOI：
10.1016/j.actbio.2017.11.020
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发表时间：
2018-01-15
影响因子：
9.7
通讯作者：
Nam, Jin
中科院分区：
文献类型：
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作者：
Brunelle, Alexander R.;Horner, Christopher B.;Nam, Jin
由于水凝胶能够将细胞包裹在仿生的三维微环境中，因此在软骨组织工程应用中显示出巨大的潜力。然而，生产具有限定尺寸的细胞/支架构建体所必需的多步制造过程限制了它们的现成的平移使用。在这项研究中，我们已经开发了一种混合支架系统，它结合了一种热敏性水凝胶，聚（乙二醇）-聚（N-异丙基丙烯酰胺）（PEG-PNIPAAm），与一种可生物降解的聚合物，聚（ε-己内酯）（PCL），到一个复合材料，静电纺丝微纤维结构。一个明智的材料组合物和静电纺丝过程的优化产生了一个结构自支撑的混合支架。PEG-PNIPAAm的反向热敏性允许其在PCL微纤维网络内的细胞接种后溶解/水合，同时在室温下保持整体支架形状。随后的温度升高到37摄氏度诱导水凝胶的相变到凝胶状态，有效地将细胞包封在3D水凝胶中而不使用模具。我们证明了杂交支架增强了基于软骨细胞基因和蛋白表达的人间充质干细胞（hMSCs）的软骨分化，这导致细胞/支架构建物具有上级粘弹性。该混合支架能够实现简单的单步细胞接种过程，以将细胞接种在具有软骨组织工程潜力的3D水凝胶内。(C)2017 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Hydrogels have shown great potential for cartilage tissue engineering applications due to their capability to encapsulate cells within biomimetic, 3-dimensional (3D) microenvironments. However, the multi-step fabrication process that is necessary to produce cell/scaffold constructs with defined dimensions, limits their off-the-shelf translational usage. In this study, we have developed a hybrid scaffolding system which combines a thermosensitive hydrogel, poly(ethylene glycol)-poly(N-isopropylacrylamide) (PEG-PNIPAAm), with a biodegradable polymer, poly(epsilon-caprolactone) (PCL), into a composite, electrospun microfibrous structure. A judicious optimization of material composition and electrospinning process produced a structurally self-supporting hybrid scaffold. The reverse thermosensitivity of PEG-PNIPAAm allowed its dissolution/hydration upon cell seeding within a network of PCL microfibers while maintaining the overall scaffold shape at room temperature. A subsequent temperature elevation to 37 degrees C induced the hydrogel's phase transition to a gel state, effectively encapsulating cells in a 3D hydrogel without the use of a mold. We demonstrated that the hybrid scaffold enhanced chondrogenic differentiation of human mesenchymal stem cells (hMSCs) based on chondrocytic gene and protein expression, which resulted in superior viscoelastic properties of the cell/scaffold constructs. The hybrid scaffold enables a facile, single-step cell seeding process to inoculate cells within a 3D hydrogel with the potential for cartilage tissue engineering. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.