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三维干细胞球体在大分子拥挤环境下制备的具有生物活性的去细胞细胞外基质可作为组织工程支架。

Bioactive Decellularized Extracellular Matrix Derived from 3D Stem Cell Spheroids under Macromolecular Crowding Serves as a Scaffold for Tissue Engineering.

机构信息

Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan.

Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

出版信息

Adv Healthc Mater. 2021 Jun;10(11):e2100024. doi: 10.1002/adhm.202100024. Epub 2021 Apr 22.

Abstract

Scaffolds for tissue engineering aim to mimic the native extracellular matrix (ECM) that provides physical support and biochemical signals to modulate multiple cell behaviors. However, the majority of currently used biomaterials are oversimplified and therefore fail to provide a niche required for the stimulation of tissue regeneration. In the present study, 3D decellularized ECM (dECM) scaffolds derived from mesenchymal stem cell (MSC) spheroids and with intricate matrix composition are developed. Specifically, application of macromolecular crowding (MMC) to MSC spheroid cultures facilitate ECM assembly in a 3D configuration, resulting in the accumulation of ECM and associated bioactive components. Decellularized 3D dECM constructs produced under MMC are able to adequately preserve the microarchitecture of structural ECM components and are characterized by higher retention of growth factors. This results in a stronger proangiogenic bioactivity as compared to constructs produced under uncrowded conditions. These dECM scaffolds can be homogenously populated by endothelial cells, which direct the macroassembly of the structures into larger cell-carrying constructs. Application of empty scaffolds enhances intrinsic revascularization in vivo, indicating that the 3D dECM scaffolds represent optimal proangiogenic bioactive blocks for the construction of larger engineered tissue constructs.

摘要

用于组织工程的支架旨在模拟提供物理支持和生化信号以调节多种细胞行为的天然细胞外基质 (ECM)。然而,目前大多数使用的生物材料过于简化,因此无法提供刺激组织再生所需的小生境。在本研究中,开发了源自间充质干细胞 (MSC) 球体的具有复杂基质组成的 3D 脱细胞 ECM (dECM) 支架。具体而言,将大分子拥挤 (MMC) 应用于 MSC 球体培养中,可促进 ECM 在 3D 配置中组装,导致 ECM 和相关生物活性成分的积累。在 MMC 下产生的脱细胞 3D dECM 构建体能够充分保留结构 ECM 成分的微观结构,并具有更高的生长因子保留率。与在非拥挤条件下产生的结构相比,这导致更强的促血管生成生物活性。这些 dECM 支架可以被内皮细胞均匀地填充,内皮细胞将结构的宏观组装成更大的细胞承载构建体。空支架的应用增强了体内的固有血管生成,表明 3D dECM 支架是构建更大工程组织构建体的最佳促血管生成生物活性块。

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