Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705.
Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705.
ACS Biomater Sci Eng. 2020 May 11;6(5):2518-2532. doi: 10.1021/acsbiomaterials.9b01067. Epub 2019 Oct 29.
Once focused exclusively on the creation of tissues to repair or replace diseased or damaged organs, the field of tissue engineering has undergone an important evolution in recent years. Namely, tissue engineering techniques are increasingly being applied to intentionally generate pathological conditions. Motivated in part by the wide gap between 2D cultures and animal models in the current disease modeling continuum, disease-inspired tissue-engineered platforms have numerous potential applications, and may serve to advance our understanding and clinical treatment of various diseases. This review will focus on recent progress toward generating tissue-engineered models of cardiovascular diseases, including cardiac hypertrophy, fibrosis, and ischemia reperfusion injury, atherosclerosis, and calcific aortic valve disease, with an emphasis on how these disease-inspired platforms can be used to decipher disease etiology. Each pathology is discussed in the context of generating both disease-specific cells as well as disease-specific extracellular environments, with an eye toward future opportunities to integrate different tools to yield more complex and physiologically relevant culture platforms. Ultimately, the development of effective disease treatments relies upon our ability to develop appropriate experimental models; as cardiovascular diseases are the leading cause of death worldwide, the insights yielded by improved disease modeling could have substantial ramifications for public health and clinical care.
组织工程学领域最初专注于创建组织来修复或替代患病或受损的器官,但近年来发生了重要演变。也就是说,组织工程技术越来越多地被应用于有意产生病理状况。受到当前疾病建模连续体中 2D 培养和动物模型之间的巨大差距的部分推动,受疾病启发的组织工程平台具有许多潜在应用,并且可能有助于推进我们对各种疾病的理解和临床治疗。本综述将重点介绍近年来在生成心血管疾病的组织工程模型方面的进展,包括心肌肥厚、纤维化和缺血再灌注损伤、动脉粥样硬化和钙化主动脉瓣疾病,并强调这些受疾病启发的平台如何用于破译疾病病因。每种病理学都在生成特定疾病的细胞和特定疾病的细胞外环境的背景下进行讨论,着眼于未来整合不同工具以产生更复杂和更符合生理的培养平台的机会。最终,有效的疾病治疗的发展依赖于我们开发适当的实验模型的能力;由于心血管疾病是全球范围内的主要死亡原因,因此改进疾病建模所带来的见解可能对公共卫生和临床护理产生重大影响。