Novel minimally-invasive in-situ 3D bioprinting platform for cardiac regeneration

据世卫组织称，目前心脏疾病（如梗死、心律失常、缺血等）是导致死亡的主要原因之一。在这个项目中，我的目标是使用跨学科的方法开发一种新的原位3D生物打印（insitubiopprint）平台，用于心脏再生，直接在宿主组织上制造患者特定的心脏贴片。这将产生新一代的3D打印自动植入方法，这将大大提高手术效果和患者的福祉。在本研究中，将设计一种微创生物3D打印平台，仅通过小切口进入组织，这完全概括了腹腔镜（锁眼手术）的概念。拟议的打印机将在打印过程中感知、学习和适应曲面，而不是遵循预先规划的打印路径，并且喷嘴-基材间隙的高度将通过阻抗光谱传感和机器学习（ML）促进的光谱分析来确定。基于该平台，导电共聚物将被合成并优化用于原位打印。最后，我将通过三种心脏模型：非活猪心脏（尺寸类似于人类心脏）、3D心肌细胞培养和冷冻损伤心律失常心肌切片模型来研究导电心脏贴片的治疗效果和再生潜力。该研究将验证临床相关的3D生物打印技术，以加速手术机器人和组织再生的转化，并最终使接受手术的患者受益。

Currently, cardiac disorders (e.g., infarction, arrythmia, ischemia, etc.) are one of the leading causes of death according to WHO. In this project I aim to use interdisciplinary approaches to develop a novel in-situ 3D bioprinting (inSituBioprint) platform for cardiac regeneration, to directly fabricate patient-specific cardiac patches on host tissue. This will produce a new generation of 3D printing method for automatic implantation, which will drastically improve the surgical outcomes and patients' well-being. In the proposed study, a minimally-invasive 3D bioprinting platform will be designed to access tissue only through small incision, which fully recapitulates the concept of laparoscopy (keyhole surgery). Rather than following pre-planned printing paths, the proposed printer will sense, learn, and adapt to the curved surface during printing, and the height of the nozzle-substrate gap will be determined via impedance spectroscopic sensing and machine learning (ML) facilitated spectra analysis. Based on this platform, the conductive copolymer will be synthesized and optimised for in situ printing. Finally, I will investigate the therapeutic efficacy and regenerative potential of the conductive cardiac patch using three cardiac models: nonviable porcine heart (dimensionally similar to human heart), 3D cardiomyocyte culture, and cryoinjured arrythmia myocardial slice model. The proposed study will validate a clinically-relevant 3D bioprinting technique to accelerate the translation of surgical robotics and tissue regeneration, and eventually to benefit patient undergoing surgeries.