Engineered Extracellular Matrices as Biomaterials of Tunable Composition and Function
Engineered Extracellular Matrices as Biomaterials of Tunable Composition and Function
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DOI：
10.1002/adfm.201605486
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发表时间：
2017-02-17
影响因子：
19
通讯作者：
Martin, Ivan
中科院分区：
文献类型：
--
作者：
Bourgine, Paul Emile;Gaudiello, Emanuele;Martin, Ivan
工程化和脱细胞的细胞外基质（ECM）作为能够通过嵌入信号的生理表现来诱导细胞生长/分化和组织修复的材料，在再生医学中受到越来越多的关注。然而，ECM 生产/脱细胞工艺及其成分的控制仍然是主要挑战。本研究报告了具有定制特性的 ECM 材料的工程设计，其基础是对在灌注流下在 3D 多孔支架内培养的永生化和可诱导死亡的人间充质基质细胞 (hMSC) 进行基因操作。该策略允许强大的 ECM 沉积和随后通过有意的细胞凋亡诱导进行脱细胞化。与标准生产和冷冻/解冻处理相比，这可以更好地保存 ECM，从而在植入颅骨缺损时增强骨形成。 ECM 组成和功能的可调性通过修改细胞系以过表达血管内皮生长因子 α (VEGF) 来例证，这导致异位植入模型中选择性 ECM 富集和出色的脉管系统募集。灌注流下的 hMSC 系培养对于使用 ECM 实现均匀的支架装饰以及简化单个环境室中的不同工程/脱细胞阶段至关重要。研究结果概述了将合适的细胞系和生物反应器系统相结合以生成基于 ECM 的现成材料的范例，以及旨在激活内源再生过程的定制信号集。
Engineered and decellularized extracellular matrices (ECM) are receiving increasing interest in regenerative medicine as materials capable to induce cell growth/differentiation and tissue repair by physiological presentation of embedded cues. However, ECM production/decellularization processes and control over their composition remain primary challenges. This study reports engineering of ECM materials with customized properties, based on genetic manipulation of immortalized and death-inducible human mesenchymal stromal cells (hMSC), cultured within 3D porous scaffolds under perfusion flow. The strategy allows for robust ECM deposition and subsequent decellularization by deliberate cell-apoptosis induction. As compared to standard production and freeze/thaw treatment, this grants superior preservation of ECM, leading to enhanced bone formation upon implantation in calvarial defects. Tunability of ECM composition and function is exemplified by modification of the cell line to overexpress vascular endothelial growth factor alpha (VEGF), which results in selective ECM enrichment and superior vasculature recruitment in an ectopic implantation model. hMSC lines culture under perfusion-flow is pivotal to achieve uniform scaffold decoration with ECM and to streamline the different engineering/decellularization phases in a single environmental chamber. The findings outline the paradigm of combining suitable cell lines and bioreactor systems for generating ECM-based off-the-shelf materials, with custom set of signals designed to activate endogenous regenerative processes.