I-Corps: 3D Bioprinted Cardiac Tissue Patch for Heart Repair

I-Corps：用于心脏修复的 3D 生物打印心脏组织补片

• 批准号: 2333048
• 负责人: Lijie Grace Zhang
• 金额: $ 5万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2333048&HistoricalAwards=false
• 关键词: Corps; 3D; Bioprinted; Cardiac; Tissue

The broader impact/commercial potential of this I-Corps project is the development of an implantable 3D bioprinted patch device that can regenerate damaged cardiac muscle tissues. The proposed technology is for the restoration of necrotic myocardial tissues resulting from a severe form of heart attack known as ST-elevated Myocardial Infarction (STEMI). Current approaches to STEMI and heart failure treatment focus primarily on restoring blood flow to the cardiac muscle, but do little to regenerate the myocardium once damaged. During a STEMI event, decreased blood flow to cardiac muscle tissue (myocardium) leads to the death of heart muscle cells known as cardiomyocytes and permanent restructuring of the heart’s microstructure. As a function of the poor inherent regenerative capacity of the myocardium, an estimated 20% of patients who suffer an initial STEMI will go on to have a second within 5 years, and up to 30% of primary-STEMI patients will develop heart failure within 1 year. The proposed technology may be a first-in-class interventionary method for the regeneration of myocardial tissues and may improve the quality of life for STEMI patients by lowering their risk of subsequent heart attacks and progression to heart failure. Moreover, the technology may spur the development of other patch-based technologies for the treatment of other debilitating fibrotic diseases.This I-Corps project is based on the development of a 3D bioprinted tissue patch technology that promotes the regeneration of cardiac muscle tissue through the delivery of patient-specific cardiac cells. This proposed technology is aimed treating necrotic myocardial tissues resulting from a severe form of heart attack known as ST-elevated Myocardial Infarction (STEMI) and employs a tri-cultured, cellularized patch system to induce myocardial tissue regeneration developed using a murine chronic myocardial infarction (MI) model. Initial results using the proposed technology demonstrated that its structural design and cellular components promoted enhanced cellular engraftment, vascularization, and increased left ventricular ejection fraction of the chronic MI model 4 months post-implantation. Upon clinical testing and approval, the proposed technology may be implanted as an adjunct material onto the infarcted myocardium of individuals undergoing a standard coronary artery bypass graft procedure to promote myocardial tissue regeneration and the restoration of cardiac output. Additionally, as a function of the versatility of the proposed technology, the 3D printed patches also may be adapted for the regeneration of other fibrotic tissues of the body, as well as function as scaffold materials for the study of various diseases and testing of pharmaceuticals in both academic and commercial settings.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该I-Corps项目的更广泛的影响/商业潜力是开发可植入的3D生物打印贴片装置，该装置可以再生受损的心肌受损。所提出的技术是为了恢复因严重的心脏病发作而被称为ST高出的心肌违规（STEMI）而导致的坏死心肌正时。当前对STEMI和心力衰竭治疗的方法主要集中在恢复流向心脏肌肉的血液流动，但一旦损坏就无法再生心肌。在STEMI事件中，流向心肌组织（心肌）的血液流量减少导致心脏肌肉细胞死亡，称为心肌细胞和心脏微观结构的永久性重组。随着心肌固有的再生能力较差的函数，估计有20％的初始STEMI患者将在5年内继续前进，并且高达30％的初级STEMI患者将在1年内发展心力衰竭。拟议的技术可能是心肌时机再生的第一类介入方法，可以通过降低其随后的心脏病发作的风险并发展为心力衰竭，从而改善STEMI患者的生活质量。此外，该技术可能会刺激其他基于斑块的技术来治疗其他令人衰弱的纤维化疾病。此I-Corps项目基于通过递送患者特异性心脏细胞的促进心肌组织的再生的3D生物打印组织贴片技术的开发。这项提出的技术的目的是治疗因严重的心脏病发作而导致的坏死性心肌时序，称为ST高出的心肌违规（STEMI）和员工使用三培养的，细胞化的贴剂系统，用于诱导使用鼠类慢性心肌intraction（MI）模型开发的心肌组织再生。使用该技术的最初结果表明，其结构设计和细胞成分促进了慢性MI模型在植入后4个月的慢性MI模型的增强的细胞植入，血管形成以及增加的左心室射血分数。经临床测试和批准后，提出的技术可以作为辅助材料植入梗塞的辅助材料，以梗塞的心肌，正在接受标准的冠状动脉搭桥移植手术，以促进心肌组织再生和心脏输出的恢复。此外，作为提出技术多功能性的函数，3D打印的贴片也可以适用于身体的其他纤维化组织的再生，以及作为脚手架材料的功能，用于研究各种疾病的研究和在学术环境中对药物进行测试的研究，以反映了NSF的范围，并反映了NSF的构建范围。影响审查标准。