Functional cardiac tissue engineering holds promise as a candidate therapy for myocardial infarction and heart failure. Generation of “strong-contracting and fast-conducting” cardiac tissue patches capable of electromechanical coupling with host myocardium could allow efficient improvement of heart function without increased arrhythmogenic risks. Towards that goal, we engineered highly functional 1 cm × 1 cm cardiac tissue patches made of neonatal rat ventricular cells which after 2 weeks of culture exhibited force of contraction of 18.0 ± 1.4 mN, conduction velocity (CV) of 32.3 ± 1.8 cm/s, and sustained chronic activation when paced at rates as high as 8.7 ± 0.8 Hz. Patches transduced with genetically-encoded calcium indicator (GCaMP6) were implanted onto adult rat ventricles and after 4–6 weeks assessed for action potential conduction and electrical integration by two-camera optical mapping of GCaMP6-reported Ca²⁺ transients in the patch and RH237-reported action potentials in the recipient heart. Of the 13 implanted patches, 11 (85%) engrafted, maintained structural integrity, and conducted action potentials with average CVs and Ca²⁺ transient durations comparable to those before implantation. Despite preserved graft electrical properties, no anterograde or retrograde conduction could be induced between the patch and host cardiomyocytes indicating lack of electrical integration. Electrical properties of the underlying myocardium were not changed by the engrafted patch. From immunostaining analyses, implanted patches were highly vascularized and expressed abundant electromechanical junctions, but remained separated from the epicardium by a non-myocyte layer. In summary, our studies demonstrate generation of highly functional cardiac tissue patches that can robustly engraft on the epicardial surface, vascularize, and maintain electrical function, but do not couple with host tissue. The lack of graft-host electrical integration is therefore a critical obstacle to development of efficient tissue engineering therapies for heart repair.

功能性心脏组织工程有望成为心肌梗塞和心力衰竭的候选疗法。能够与宿主心肌机电耦合的“强收缩且快速传导”的心脏组织贴片的产生，可以有效改善心脏功能，而不会增加致心律失常的风险。为了实现这个目标，我们设计了由新生大鼠心室细胞制成的功能强大的1 cm×1 cm心脏组织贴片，培养2周后其收缩力为18.0±1.4 mN，传导速度（CV）为32.3±1.8 cm / s ，并以8.7±0.8 Hz的频率跳动时持续持续的慢性激活。贴片中出现^2+次瞬变，RH237报告了受体心脏中的动作电位。在13个植入的贴片中，有11个（85％）被植入，保持结构完整性，并以平均CV和Ca ²⁺进行动作电位瞬时持续时间与植入前相当。尽管保留了移植物的电特性，但在贴片和宿主心肌细胞之间未诱导出顺行或逆行传导，表明缺乏电整合。植入的贴片未改变基础心肌的电学性质。通过免疫染色分析，植入的贴片高度血管化并表达丰富的机电连接，但仍通过非肌细胞层与心外膜分开。总而言之，我们的研究表明可以产生功能强大的心脏组织斑块，这些斑块可以牢固地植入心外膜表面，血管化并保持电功能，但不与宿主组织结合。