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Fast Automated Approach for the Derivation of Acellular Extracellular Matrix Scaffolds from Porcine Soft Tissues
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2020-06-15 , DOI: 10.1021/acsbiomaterials.0c00265
Andreea Badileanu 1, 2 , Camilo Mora-Navarro 1, 2 , Ana M. Gracioso Martins 1, 2 , Mario E. Garcia 1 , Daphne Sze 1, 2 , Emily W. Ozpinar 1, 2 , Lewis Gaffney 1, 2 , Jeffrey R. Enders 3, 4 , Ryan C. Branski 5 , Donald O. Freytes 1, 2
Affiliation  

Decellularized extracellular matrix (ECM) scaffolds derived from tissues and organs are complex biomaterials 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 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 adds 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 aimed 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 was a closed semibatch bioreactor system with automated dosing of decellularization reagents capable of deriving ECM material from pretreated 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.

中文翻译:

快速自动化的方法从猪软组织衍生脱细胞的细胞外基质支架。

来源于组织和器官的脱细胞细胞外基质(ECM)支架是用于临床和研究应用的复杂生物材料。已经描述了许多用于ECM生物材料衍生的脱细胞方案,每种方案适用于特定的组织和用途,从而限制了材料之间的比较。ECM产品变异性的主要来源之一是组织来源和动物年龄。尽管可以使用已建立的组织来源将这种可变性减至最小,但其他来源也来自脱细胞过程本身。总体而言,当前的方案需要人工操作,并且在试剂的选择,添加的顺序和暴露时间方面标准化较差。这些因素的组合增加了影响批次之间最终产品均匀性的可变性。此外,需要针对每种组织和组织来源优化每种方案,从而难以进行组织之间的比较。ECM支架开发的自动化和标准化构成了对当前生物制造技术的重大改进,但探索程度仍然很低。这项研究的目的是开发一种生物加工方法,以快速,自动地推导用于ECM水凝胶生产的原料,同时保留ECM组成并控制批次之间的差异。主要结果是一个封闭的半间歇式生物反应器系统,该系统具有自动计量的脱细胞试剂,能够从预处理的软组织中提取ECM材料。将ECM进一步加工成水凝胶,以证明其凝胶化和细胞相容性。这项工作提出了一种多功能,可扩展的,
更新日期:2020-07-13
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