School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
J Mater Chem B. 2020 Sep 14;8(34):7571-7590. doi: 10.1039/d0tb01528h. Epub 2020 Jul 29.
Cardiovascular diseases, including myocardial infarction (MI), persist as the leading cause of mortality and morbidity worldwide. The limited regenerative capacity of the myocardium presents significant challenges specifically for the treatment of MI and, subsequently, heart failure (HF). Traditional therapeutic approaches mainly rely on limiting the induced damage or the stress on the remaining viable myocardium through pharmacological regulation of remodeling mechanisms, rather than replacement or regeneration of the injured tissue. The emerging alternative regenerative medicine-based approaches have focused on restoring the damaged myocardial tissue with newly engineered functional and bioinspired tissue units. Cardiac regenerative medicine approaches can be broadly categorized into three groups: cell-based therapies, scaffold-based cardiac tissue engineering, and scaffold-free cardiac tissue engineering. Despite significant advancements, however, the clinical translation of these approaches has been critically hindered by two key obstacles for successful structural and functional replacement of the damaged myocardium, namely: poor engraftment of engineered tissue into the damaged cardiac muscle and weak electromechanical coupling of transplanted cells with the native tissue. To that end, the integration of micro- and nanoscale technologies along with recent advancements in stem cell technologies have opened new avenues for engineering of structurally mature and highly functional scaffold-based (SB-CMTs) and scaffold-free cardiac microtissues (SF-CMTs) with enhanced cellular organization and electromechanical coupling for the treatment of MI and HF. In this review article, we will present the state-of-the-art approaches and recent advancements in the engineering of SF-CMTs for myocardial repair.
心血管疾病，包括心肌梗死（MI），仍然是全球死亡和发病的主要原因。心肌的有限再生能力对 MI 及随后的心衰（HF）的治疗提出了重大挑战。传统的治疗方法主要依赖于通过药理学调节重塑机制来限制诱导的损伤或对剩余存活心肌的压力，而不是损伤组织的替代或再生。新兴的基于再生医学的替代方法侧重于用新设计的具有功能性和仿生组织单元的组织来修复受损的心肌组织。心脏再生医学方法可大致分为三组：基于细胞的疗法、基于支架的心脏组织工程和无支架心脏组织工程。然而，尽管取得了重大进展，但这些方法的临床转化受到两个关键障碍的严重阻碍，即：工程组织在受损心肌中的植入效果差，以及移植细胞与原生组织的电机械耦合力弱。为此，微纳技术的结合以及干细胞技术的最新进展为基于支架的（SB-CMTs）和无支架心脏微组织（SF-CMTs）的结构成熟和高度功能性的工程设计开辟了新途径，具有增强的细胞组织和电机械耦合力，用于治疗 MI 和 HF。在这篇综述文章中，我们将介绍用于心肌修复的 SF-CMT 工程的最新进展和现状。
