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

这个I-Corps项目更广泛的影响/商业潜力是开发一种可植入的3D生物打印贴片设备，可以再生受损的心肌组织。 所提出的技术是用于恢复由称为ST段抬高型心肌梗死（STEMI）的严重心脏病发作引起的坏死心肌组织。 目前STEMI和心力衰竭治疗的方法主要集中在恢复心肌的血流，但对受损心肌的再生作用甚微。 在STEMI事件期间，流向心肌组织（心肌）的血流减少导致称为心肌细胞的心肌细胞死亡和心脏微结构的永久性重构。由于心肌固有的再生能力差，估计20%的初次STEMI患者将在5年内发生第二次STEMI，高达30%的初次STEMI患者将在1年内发生心力衰竭。 所提出的技术可能是心肌组织再生的一流介入方法，并可能通过降低后续心脏病发作和进展为心力衰竭的风险来改善STEMI患者的生活质量。此外，该技术可能会刺激其他基于贴片的技术的开发，用于治疗其他衰弱性纤维化疾病。I-Corps项目基于3D生物打印组织贴片技术的开发，该技术通过输送患者特定的心脏细胞来促进心肌组织的再生。 该提出的技术旨在治疗由称为ST段抬高型心肌梗死（STEMI）的严重形式的心脏病发作引起的坏死心肌组织，并采用三培养的细胞化贴片系统来诱导使用鼠慢性心肌梗死（MI）模型开发的心肌组织再生。 使用所提出的技术的初步结果表明，其结构设计和细胞组分促进了植入后4个月慢性MI模型的增强的细胞植入、血管化和增加的左心室射血分数。 在临床测试和批准后，所提出的技术可以作为辅助材料植入到经历标准冠状动脉旁路移植手术的个体的梗塞心肌上，以促进心肌组织再生和心输出量的恢复。另外，根据所提出的技术的多功能性，3D打印贴片还可以适于身体的其他纤维化组织的再生，以及在学术和商业环境中作为各种疾病研究和药物测试的支架材料。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准。

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.