人心脏组织芯片构建的新方法及在药物评估应用中的研究

Organ-on-a-chip is a recently developed new research direction in biomedical engineering, aiming at construction of human organoids to mimic the physiological or pathological characteristics of human tissues/organs through integration of stem cells, biomaterials, tissue engineering, microfluidics and microfabrication techniques. The technical development of the organ-on-a-chip is of great significance in drug research & development as well as in basic medical investigations. The heart-on-a-chip is the most core part of human organ-on-a-chip. This proposal will construct multiple functional microfluidic chip system that includes electrostimulation, electric signal and force signal detections. In the chip, a variety of cell types will be implanted step by step in the three-dimensional gradient biomimic hydrogel scafolds, which is stimulated with electric signals in situ to facilitate the formation of functional myocardium. Furthermore, the constructed human heart tissue chip will be applied for evaluating drug safety and for establishing animal models of heart diseases to test drug effectiveness. The results to be obtained from this study will provide novel insights for heart chip construction, and new technology for achieving low-cost drug testing platform with high efficiency. This study will establish a foundation for future drug development and research, as well as for studying the pathogenesis of serious diseases.

器官芯片是近年来生物医学工程的一个新兴的研究方向，其目标是通过干细胞、生物材料、组织工程、微流控和微加工等技术的交叉融合，在芯片上构建可模拟人体组织器官的生理或病理特性的人体类器官。器官芯片技术的发展，对新药研发和医学基础研究具有重要意义。心脏芯片是人体器官芯片中的最核心部分。本项目将构建集电刺激及电信号和力信号检测于一体的多功能微流控芯片系统，在芯片内模拟人体心脏微环境和心肌组织结构，将多种细胞分步植入芯片内三维梯度交联水凝胶仿生支架，原位施加电刺激促进功能性心肌组织形成。利用所构建的人心脏组织芯片对药物进行安全性评估，并在芯片系统内建立心脏疾病模型，实现对药物疗效的评价。研究结果将为心脏芯片的构建提供新思路，为获得低成本高效的药物检测平台提供新技术。该研究将为未来新药研发和重大疾病发病机制的研究奠定基础。

器官芯片是当前生物医学工程的一个新兴的研究方向，其目标是通过干细胞、生物材料、组织工程、微流控和微加工等技术的交叉融合，在芯片上构建可模拟人体组织器官的生理或病理特性的人体类器官。器官芯片技术的发展，对新药研发和医学基础研究具有重要意义。心脏芯片是人体器官芯片中的核心部分。本项目构建了集电刺激及电信号和力信号检测于一体的多功能微流控心脏芯片系统，在芯片内模拟人体心脏微环境和心肌组织结构，将人iPSCs分化的心肌细胞等多种细胞植入芯片内的水凝胶仿生支架进行动态培养，原位施加电刺激促进了心肌细胞成熟和功能性心肌组织形成，并实现了对心肌收缩功能和电生理功能的原位实时检测。利用已知药物验证了该芯片平台用于药物疗效检测和心脏毒性评估的可靠性。在芯片系统内通过改变组织微环境或者采用疾病特异性iPSCs分化的心肌细胞获得了具有病理特性的心脏组织，建立了体现疾病表型特征的心脏疾病模型。研究结果为获得低成本高效的药物检测平台提供了新技术，为未来新药研发和重大疾病发病机制的研究奠定基础。