3D打印角膜基质透镜及其角膜基质内植入的研究

Previous studies in animal models and clinical patients have showed that the femtosecond laser-assisted intrastromal lenticule implantation can increase corneal stromal thickness and change corneal refractive power. The results indicated that intrastromal lenticule implantation could be a promising and effective procedure to correct high myopia, hyperopia, presbyopia and treat keratoconus without significant adverse effects. However, it is significant restrained by the sources of the corneal lenticules and many sources of deficiencies. The research and development of lenticules have not been reported so far. We intend to use 3D printing technology to print personalized lenticules, which can be used to correct high myopia, hyperopia, presbyopia and treat keratoconus. During preliminary work, we used polyethylene glycol diacrylate (PEGDA) and carboxymethyl cellulose (CMC) as main materials to print lenticule and implantated in the cornea of New Zealand rabbits. The result showed that these 3D printed lenticules were clear and no complications were observed. We will design lenticules according to the rhesus corneal refractive status and use 3D printer to print out personalized lenticules with these two main materials, which may provide a useful method for treatment of high myopia, hyperopia, presbyopia and keratoconus.

动物实验及临床研究表明飞秒激光辅助的角膜基质透镜植入术可增加角膜厚度、改变角膜的屈光状态及增加角膜的生物力学强度，能为超高度近视、远视、老视及圆锥角膜的治疗提供新的思路。但人的角膜基质透镜来源有限且存在诸多不足，其应用受限。基质透镜的研发，迄今国内外尚无报道。本课题组拟用3D打印技术打印个性化基质透镜，为临床超高度近视、远视、老视及圆锥角膜的治疗提供新的方法。预实验中，我们以聚乙二醇双丙烯酸酯（PEGDA）及羧甲基纤维素（CMC）为主原料打印基质透镜并进行新西兰兔眼角膜基质透镜植入，发现这两种原料打印出的基质透镜透明，植入兔眼角膜基质后无排斥反应且不与角膜基质融合等特点。本课题组将以这两种材料为主原料，根据恒河猴眼角膜屈光状态设计并用3D打印机打印出个性化的基质透镜，在基质透镜中负载角膜基质细胞，进行恒河猴角膜基质内植入，观察恒河猴眼角膜状态，为临床上屈光不正及圆锥角膜的治疗提供依据。

项目早期在完善基质透镜性能的基础上，成功将基质透镜植入兔角膜基质口袋中，早期并未出现排斥反应，并且在基质透镜上成功初步负载角膜基质细胞及角膜上皮细胞。但由于中美关系恶化等不可控因素，由美国加州大学圣地亚哥分校眼科研究所所长张康教授实验室提供的技术支持和基质透镜出现中断，之后不断寻找新的技术合作，目前尚未获得实质性进展。但在该项目的支持下，我们进行了屈光手术相关基础和临床研究，包括了全飞秒术后早期愈合反应研究、屈光手术术后视觉质量研究、圆锥角膜进行个性化切削联合角膜交联术后临床效果研究及采用人工智能辅助下进行圆锥角膜术前地形图筛查研究，共发表SCI论文12篇，其中人工智能相关文章已发表于JAMA Ophthalmology。同时，在该项目支持下，共培养博士5名，硕士1名。