Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-05-25 , DOI: 10.1016/j.actbio.2020.05.031 Michaela W McCrary 1 , Deanna Bousalis 1 , Sahba Mobini 2 , Young Hye Song 3 , Christine E Schmidt 1
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Biomedical engineers are at the forefront of developing novel treatments to improve human health, however, many products fail to translate to clinical implementation. In vivo pre-clinical animal models, although the current best approximation of complex disease conditions, are limited by reproducibility, ethical concerns, and poor accurate prediction of human response. Hence, there is a need to develop physiologically relevant, low cost, scalable, and reproducible in vitro platforms to provide reliable means for testing drugs, biomaterials, and tissue engineered products for successful clinical translation. One emerging approach of developing physiologically relevant in vitro models utilizes decellularized tissues/organs as biomaterial platforms for 2D and 3D models of healthy and diseased tissue. Decellularization is a process that removes cellular content and produces tissue-specific extracellular matrix scaffolds that can more accurately recapitulate an organ/tissue's native microenvironment compared to other natural or synthetic materials. Decellularized tissues hold enormous potential for in vitro modeling of various disease phenotypes and tissue responses to drugs or external conditions such as aging, toxin exposure, or even implantation. In this review, we highlight the need for in vitro models, the advantages and limitations of implementing decellularized tissues, and considerations of the decellularization process. We discuss current research efforts towards applying decellularized tissues as platforms to generate in vitro models of healthy and diseased tissues, and where we foresee the field progressing. A variety of organs/tissues are discussed, including brain, heart, kidney, large intestine, liver, lung, skeletal muscle, skin, and tongue.
Statement of Significance
Many biomedical products fail to reach clinical translation due to animal model limitations. Development of physiologically relevant in vitro models can provide a more economic, scalable, and reproducible means of testing drugs/therapeutics for successful clinical translation. The use of decellularized tissues as platforms for in vitro models holds promise, as these scaffolds can effectively replicate native tissue complexity, but is not widely explored. This review discusses the need for in vitro models, the promise of decellularized tissues as biomaterial substrates, and the current research applying decellularized tissues towards the creation of in vitro models. Further, this review provides insights into the current limitations and future of such in vitro models.
中文翻译：
去细胞组织作为健康和患病组织体外建模的平台。
生物医学工程师站在开发改善人类健康的新疗法的最前沿，但是，许多产品未能转化为临床应用。尽管目前对复杂疾病状况的最佳逼近度，体内临床前动物模型仍受到可重复性，道德问题和对人类反应的准确预测的限制。因此，需要开发生理相关的，低成本的，可扩展的和可再现的体外平台，以提供可靠的手段来测试药物，生物材料和组织工程产品以成功进行临床翻译。一种开发与生理相关的体外方法该模型利用脱细胞的组织/器官作为健康和患病组织的2D和3D模型的生物材料平台。去细胞化是去除细胞内容物并产生组织特异性细胞外基质支架的过程，与其他天然或合成材料相比，该支架可以更准确地概括器官/组织的天然微环境。去细胞的组织在各种疾病表型的体外建模以及组织对药物或外部条件（例如衰老，毒素暴露或什至植入）的反应方面具有巨大潜力。在这篇评论中，我们强调了体外的需求模型，实施脱细胞组织的优势和局限性以及对脱细胞过程的考虑。我们讨论了当前的研究工作，以应用脱细胞的组织为平台来生成健康和患病组织的体外模型，并预测了该领域的进展。讨论了多种器官/组织，包括脑，心脏，肾脏，大肠，肝，肺，骨骼肌，皮肤和舌头。
重要声明
由于动物模型的限制，许多生物医学产品无法实现临床翻译。生理相关的体外模型的开发可以提供更经济，可扩展且可重现的测试药物/疗法的方法，以成功进行临床翻译。使用脱细胞组织作为体外模型的平台有希望，因为这些支架可以有效地复制天然组织的复杂性，但并未得到广泛研究。这篇评论讨论了体外模型的需求，脱细胞组织作为生物材料基质的前景以及当前将脱细胞组织应用于体外创建的研究楷模。此外，本综述提供了对这种体外模型的当前局限性和未来的见解。
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