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

目前，心脏疾病（例如，梗塞、心律失常、局部缺血等）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来开发一种新的原位3D生物打印（inSituBioprint）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。这将产生新一代用于自动植入的3D打印方法，这将大大改善手术结果和患者的健康。在拟议的研究中，将设计一个微创3D生物打印平台，仅通过小切口进入组织，这完全概括了腹腔镜（锁孔手术）的概念。不是遵循预先计划的打印路径，所提出的打印机将在打印期间感测、学习和适应弯曲表面，并且将经由阻抗光谱感测和机器学习（ML）促进的光谱分析来确定基板-基板间隙的高度。基于这个平台，导电共聚物将被合成并优化用于原位印刷。最后，我将使用三种心脏模型研究导电心脏贴片的治疗效果和再生潜力：无活力的猪心（尺寸类似于人类心脏），3D心肌细胞培养和冷冻损伤的心律失常心肌切片模型。这项拟议的研究将验证一种临床相关的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.