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

目前，心脏疾病(如梗塞、心律失常、缺血等)根据世卫组织的说法，是主要的死亡原因之一。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型的原位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补片。这将产生用于自动植入的新一代3D打印方法，将极大地改善手术结果和患者的福祉。在这项拟议的研究中，一个微创的3D生物打印平台将被设计成只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。该打印机将在打印过程中感应、学习并适应曲面，而不是遵循预先规划的打印路径，喷嘴-基板间隙的高度将通过阻抗谱传感和机器学习(ML)促进的频谱分析来确定。在此平台的基础上，将合成导电共聚物，并对其进行优化以用于原位打印。最后，我将使用三种心脏模型：非存活的猪心(尺寸与人类心脏相似)、三维心肌细胞培养和冷冻损伤的心律失常心肌切片模型来研究导电心脏补片的治疗效果和再生潜力。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换，并最终使正在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.