胰岛的液滴微流体包裹和深度过冷保存的机理及其调控

I型糖尿病是威胁人类健康的重大慢性疾病，胰岛微胶囊是其最有前景的治疗途径之一，其核心挑战是胰岛微胶囊的安全制备及其在体外的长期保存。但现有的微包裹技术难以控制微包裹时的流场，胰岛的形态和活性容易被破坏；由于过冷生物样品中冰晶形成的限制，现有的胰岛保存温度高，保存时间短。因此，结合申请人在流体力学、热力学及生物医学工程中的研究基础，本项目拟：开发三维液滴微流体器件，调控微液滴中的流场分布和微胶囊的运动轨迹，实现胰岛在水凝胶微胶囊中安全高效的包裹；通过油相密封技术，揭示过冷胰岛中晶核形成的规律和机制；通过抑制胰岛过冷保存中晶核形成的机制，降低胰岛保存温度，实现胰岛的“深度过冷”保存；通过动物体内的胰岛移植实验，验证胰岛在液滴微流体中安全包裹及其在体外“深度过冷”长期保存的有效性。本项目的研究成果将发展胰岛的水凝胶微包裹和体外保存方法，为利用胰岛微胶囊治疗I型糖尿病提供关键的技术支撑。

Type 1 diabetes mellitus (T1DM) is a major chronic disease that threatens human health, and islet microcapsule is one of the most promising curing methods with two core challenges: islet safe microencapsulation and long-term in vitro preservation. Due to the difficulty of precise flow field control, current microencapsulation methods compromise the morphology and viability of encapsulated islets; due to the limitation of ice formation in supercooled biospecimens and high preservation temperatures, current preservation methods of islets have short preservation periods. Therefore, based on our research foundation on fluid mechanics, thermodynamics, and biomedical engineering, this project aims to: develop 3D droplet-based microfluidic devices, control the flow field and trajectory of microcapsules, and realize the safe and efficient hydrogel microencapsulation for islets; reveal mechanisms of ice nucleation in supercooled islets via oil sealing methods; decrease islet preservation temperatures by inhibiting ice nucleation mechanisms, and achieve islet "deep-supercooling" (DSC) preservation; perform in vivo islet allotransplantation trials to confirm the efficacy of hydrogel encapsulated and DSC preserved islets. The results of this project would develop the hydrogel encapsulation method and in vitro preservation method of islet, providing key technological supports for islet microcapsules to cue T1DM.