Fast Automated Approach for the Derivation of Acellular Extracellular Matrix Scaffolds from Porcine Soft Tissues.

Fast Automated Approach for the Derivation of Acellular Extracellular Matrix Scaffolds from Porcine Soft Tissues.
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DOI:
10.1021/acsbiomaterials.0c00265
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发表时间:
2020-07-13
影响因子:
5.8
通讯作者:
Freytes DO
Freytes DO
中科院分区:
工程技术2区
文献类型:
--
作者:
Badileanu A;Mora-Navarro C;Gracioso Martins AM;Garcia ME;Sze D;Ozpinar EW;Gaffney L;Enders JR;Branski RC;Freytes DO

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脱细胞细胞外基质(ECM)支架是源自临床和研究应用中使用的组织和器官的复杂生物材料。已经描述了许多用于 ECM 生物材料衍生的脱细胞化方案,每种方案都适合特定的组织和用途,限制了材料之间的比较。 ECM 产品变异的主要来源之一来自组织来源和动物年龄。尽管可以通过使用已建立的组织来源来最小化这种变异性,但其他来源是由脱细胞过程本身产生的。总体而言,当前的方案需要手动工作,并且在试剂的选择、添加顺序和暴露时间方面标准化较差。这些因素的结合增加了影响批次之间最终产品均匀性的可变性。此外,每个协议都需要针对每个组织和组织来源进行优化,这使得组织与组织之间的比较变得困难。 ECM 支架开发的自动化和标准化是对当前生物制造技术的重大改进,但仍缺乏探索。本研究旨在开发一种生物制造方法,用于快速、自动化地衍生 ECM 水凝胶生产原材料,同时保留 ECM 成分并控制批次间的变异性。主要结果是一个封闭的半间歇式生物反应器系统,具有自动计量脱细胞试剂的能力,能够从预处理的软组织中提取 ECM 材料。 ECM 进一步加工成水凝胶,以证明凝胶化和细胞相容性。这项工作为 ECM 支架的快速生产提供了一个多功能、可扩展和自动化的平台。
Decellularized extracellular matrix (ECM) scaffolds are complex biomaterials derived from tissues and organs used in clinical and research applications. A number of decellularization protocols have been described for ECM biomaterials derivation, each adapted to a particular tissue and use, restricting comparisons among materials. One of the major sources of variability in ECM products comes from the tissue source and animal age. Although this variability could be minimized by using established tissue sources, other sources arise from the decellularization process itself. Overall, current protocols require manual work and are poorly standardized with regard to the choice of reagents, the order by which they are added, and exposure times. The combination of these factors add variability affecting the uniformity of the final product between batches. Furthermore, each protocol needs to be optimized for each tissue and tissue source making tissue-to-tissue comparisons difficult. Automation and standardization of ECM scaffold development constitute a significant improvement to current biomanufacturing techniques but remains poorly explored. This study aims to develop a biofabrication method for fast and automated derivation of raw material for ECM hydrogel production while preserving ECM composition and controlling lot-to-lot variability. The main result is a closed semi-batch bioreactor system with automated dosing of decellularization reagents capable of deriving ECM material from pre-treated soft tissues. The ECM was further processed into hydrogels to demonstrate gelation and cytocompatibility. This work presents a versatile, scalable, and automated platform for the rapid production of ECM scaffolds.
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