Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston Methodist, Houston, TX, USA; Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX, USA; Texas A&M MD/PhD Program, Texas A&M Health Science Center, College Station, TX, USA.
Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston Methodist, Houston, TX, USA; Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, (MI), Italy.
Nanomedicine. 2021 Apr;33:102367. doi: 10.1016/j.nano.2021.102367. Epub 2021 Feb 5.
Cardiovascular diseases are the number one killer in the world. Currently, there are no clinical treatments to regenerate damaged cardiac tissue, leaving patients to develop further life-threatening cardiac complications. Cardiac tissue has multiple functional demands including vascularization, contraction, and conduction that require many synergic components to properly work. Most of these functions are a direct result of the cardiac tissue structure and composition, and, for this reason, tissue engineering strongly proposed to develop substitute engineered heart tissues (EHTs). EHTs usually have combined pluripotent stem cells and supporting scaffolds with the final aim to repair or replace the damaged native tissue. However, as simple as this idea is, indeed, it resulted, after many attempts in the field, to be very challenging. Without design complexity, EHTs remain unable to mature fully and integrate into surrounding heart tissue resulting in minimal in vivo effects. Lately, there has been a growing body of evidence that a complex, multifunctional approach through implementing scaffold designs, cellularization, and molecular release appears to be essential in the development of a functional cardiac EHTs. This review covers the advancements in EHTs developments focusing on how to integrate contraction, conduction, and vascularization mimics and how combinations have resulted in improved designs thus warranting further investigation to develop a clinically applicable treatment.
心血管疾病是世界头号杀手。目前，临床上尚无治疗方法可修复受损的心脏组织，导致患者出现进一步危及生命的心脏并发症。心脏组织具有多种功能需求，包括血管生成、收缩和传导，这些功能需要许多协同成分才能正常工作。这些功能大多直接来自于心脏组织的结构和组成，因此，组织工程强烈建议开发替代工程心脏组织（EHT）。EHT 通常结合多能干细胞和支持性支架，最终目的是修复或替代受损的天然组织。然而，尽管这个想法很简单，但实际上，在该领域进行了许多尝试之后，发现这非常具有挑战性。如果没有设计的复杂性，EHT 仍然无法完全成熟并整合到周围的心脏组织中，导致体内效果很小。最近有越来越多的证据表明，通过实施支架设计、细胞化和分子释放的复杂多功能方法，对于开发功能性心脏 EHT 至关重要。本综述介绍了 EHT 发展方面的进展，重点介绍了如何整合收缩、传导和血管生成模拟，以及这些组合如何导致改进的设计，从而值得进一步研究以开发临床适用的治疗方法。
