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

开发心脏组织和可生物降解电子器件的混合体，用于具有在线监测和刺激功能的心脏植入物

• 批准号: 9757761
• 负责人: Cunjiang Yu
• 金额: $ 20.66万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9757761
• 关键词: 3-Dimensional; Adopted; Anastomosis - action; Biologic Development; Biology; Blood; Blood Vessels; Cardiac; Cardiac Myocytes; Electric Stimulation; Electrodes; Electronics; Endothelial Cells; Engineering; Ensure; Exhibits; Generations; Goals; Heart; Heart Diseases; Histocompatibility; Human; Human body; Hybrids; Implant; In Situ; In Vitro; Metabolic Pump; Methods; Microfluidics; Monitor; Myocardial tissue; Natural regeneration; Nature; Nutrient; Organ; Oxygen; Pattern; Recovery; Regenerative Medicine; Research Personnel; Scheme; Signal Transduction; Stretching; Technology; Thick; Time; Tissue Engineering; Tissues; Vascular System; Vascularization; Waste Products; base; bioprinting; cardiac tissue engineering; design; extracellular; flexibility; flexible electronics; heart damage; heart function; implantation; improved; improved functioning; induced pluripotent stem cell; injured; innovation; multi-electrode arrays; multidisciplinary; non-compliance; novel; oxygen transport; prevent; sensor

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.

摘要 心脏作为人体最重要的器官之一，发挥着强大的生物泵的作用， 通过血管系统向/从所有其他器官输送/回收血液。因此， 再生受伤或患病心脏的能力一直是组织工程学和 再生医学。在过去的几十年里，心脏组织工程领域已经看到了 在构建功能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特性， 但挑战依然存在，包括心肌细胞的排列和它们的组织成束 将微血管网络引入工程厚壁心脏组织。《节拍》 心肌细胞是另一个主要障碍。当心肌细胞在心脏中同步跳动时， 在体外操作过程中，能力很容易丧失。基于电刺激和包含的方法 改善工程心脏自发性和同步性的导电材料 已经提出了组织，这些组织对于成功整合这些工程心脏至关重要 组织与宿主实现功能性再生。然而，最常用的方法 应用成对电极或多电极阵列等电刺激的能力受到限制 与工程心脏组织整合，用于再生，由于僵硬，不合规 这些电极的性质。软性、柔性和可伸缩电子产品领域的最新进展 提供了将兼容的电子设备与包括心脏的人体器官接口的有效手段， 它们很少被改装成与工程组织结合以改善功能。的总目标是 这项拟议的项目是开发一种软性可伸展网络成型的电子产品和生物打印的混合体 心脏组织，用于适形、原位电刺激和记录心脏信号，其中 可伸缩网络格式化电子产品将设计为可生物降解，以匹配 再生和心脏组织与嵌入的血管系统对齐将使用一种新的 微流控生物打印策略。

项目成果

Micropore‐Forming Gelatin Methacryloyl (GelMA) Bioink Toolbox 2.0: Designable Tunability and Adaptability for 3D Bioprinting Applications

Micropore™ 形成明胶甲基丙烯酰 (GelMA) Bioink Toolbox 2.0：针对 3D 生物打印应用的可设计可调性和适应性

• DOI: 10.1002/smll.202106357
• 发表时间: 2022
• 期刊: Small
• 影响因子: 13.3
• 作者: Yi, Sili;Liu, Qiong;Luo, Zeyu;He, Jacqueline Jialu;Ma, Hui‐Lin;Li, Wanlu;Wang, Di;Zhou, Cuiping;Garciamendez, Carlos Ezio;Hou, Linxi
• 通讯作者: Hou, Linxi

A wireless spinal stimulation system for ventral activation of the rat cervical spinal cord.

• DOI: 10.1038/s41598-021-94047-1
• 发表时间: 2021-07-21
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Hogan MK;Barber SM;Rao Z;Kondiles BR;Huang M;Steele WJ;Yu C;Horner PJ
• 通讯作者: Horner PJ