Developing Hybrids of Cardiac Tissue and Biodegradable Electronics Towards Heart Implants with On-line Monitoring and Stimulating Functions

摘要 作为人体最重要的器官之一，心脏作为一个有效的生物泵， 通过血管系统向/从所有其他器官输送/输送血液。结果导致 再生受伤或患病心脏的能力一直是组织工程的焦点， 再生医学在过去的几十年里，心脏组织工程领域已经看到 在制造功能性心脏组织方面取得了巨大进展，这些组织在很大程度上概括了心脏的生物学， 但挑战仍然存在，包括心肌细胞的排列和它们的组织成束 将微血管网络引入到工程化的厚心脏组织中。跳动 心肌细胞是另一个主要障碍。虽然心肌细胞在心脏中同步跳动， 在体外操作过程中，容量很容易损失。基于电刺激的方法， 促进工程心脏自发同步搏动的生物材料 组织已经提出，这是至关重要的成功整合这些工程心脏 组织与宿主实现功能性再生。然而，最常用的方法 施加诸如成对电极或多电极阵列的电刺激的能力有限 与工程化心脏组织整合，用于再生应用， 这些电极的性质。在柔软的柔性和可拉伸的电子器件领域中的最新进展 提供了将顺应性电子设备与包括心脏在内的人体器官连接的有效手段， 其很少适于与工程组织联合收割机结合以改善功能。的总目标 该项目旨在开发一种柔性可拉伸网络型电子产品和生物打印的混合物。 用于适形的、原位电刺激和记录心脏信号的心脏组织，其中， 可拉伸网络格式的电子产品将被设计成可生物降解的，以匹配生物降解的速率。 再生和心脏组织与嵌入的脉管系统对齐将使用一种新的 微流体生物打印策略。

Abstract As one of the most vital organs in the human body, the heart functions as a potent biological pump that actively delivers/recycles the blood towards/from all other organs through the vascular system. As a result, the capability to regenerate an injured or diseased heart has always been a focus in tissue engineering and regenerative medicine. Over the past few decades, the field of cardiac tissue engineering has seen tremendous progress in fabricating functional cardiac tissues that largely recapitulate the biology of the heart, but challenges remain, including the alignment of cardiomyocytes and their organization into bundles as well as the introduction of microvascular networks into engineered thick cardiac tissues. Beating of the cardiomyocytes poses another major obstacle. While cardiomyocytes beat synchronously in the heart, such capacity can be easily lost during in vitro manipulation. Methods based on electric stimulation and inclusion of electroconductive materials that improve the spontaneous and synchronous beating of engineered heart tissues have been proposed, which are critical to the successful integration of these engineered cardiac tissues with host to achieve functional regeneration. However, the most commonly used approaches for applying the electrical stimulation such as paired electrodes or multi-electrode arrays are limited in their ability to integrate with engineered cardiac tissues for applications in regeneration due to the stiff, non-compliant nature of these electrodes. Recent advances in the field of soft flexible and stretchable electronics have provided effective means to interface compliant electronic devices with human organs including the heart, which have rarely been adapted to combine with engineered tissues for improved functions. The overall goal of this proposed project is to develop a hybrid of soft stretchable network fashioned electronics and bioprinted cardiac tissue for conformal, in situ electrical stimulation and recording of cardiac signals, where the stretchable network formatted electronics will be designed to be biodegradable to match the rate of regeneration and the cardiac tissue aligned with embedded vasculature will be generated using a novel microfluidic bioprinting strategy.