层状结构仿生角膜修复材料的制备及其研究

Keratopathy is one of the main blindness causing diseases in China and about 4 million patients lose their sight due to a variety of corneal diseases. Clinically, due to the increasing maturity of corneal repair and transplantation technology, corneal repair materials which have high biological activity, biocompatibility as well as physiological function similar to corneal are therefore in a great demand. In this study, corneal repair materials with high bioactivity and function, which processes bionic composition, structure and surface to corneal were developed. The corneal repair materials were based on biodegradable polymer materials, such as collagen etc, with layered structure and surface modified using the biomimetic functional technology to regulate and mediate cell-specific recognition. This study investigated the material structure, biological functions of the surface and the interaction between the materials and corneal epithelial cells. These results have suggested that the materials developed in this study have clinical potential to repair corneal.

角膜病是我国主要的致盲眼病之一。目前，我国约有400万因各种角膜病致盲的患者，国内外尚无在临床上应用的角膜修复材料产品，而角膜修复和移植术等技术日趋成熟，迫切需要既具高生物活性、高生物相容性，又兼具角膜生理功能的修复材料。本项目基于对角膜生理功能与结构之间关系的认识，通过成分、结构和表面的多手段仿生开发出具有高度生物活性和功能的角膜修复材料。针对具有较大临床应用前景的胶原、多糖等可降解高分子材料进行层状结构的仿生构建，发展表面仿生功能化技术赋予其调控与介导细胞特异性识别的生物学功能，最终实现结构和性能与角膜组织相匹配的新型修复材料。系统研究构建类似角膜层状结构的过程机理及其性能，探讨表面仿生功能化的规律，研究修复材料与角膜上皮细胞的分化生长之间相互作用机制，通过揭示上述关键科学问题，为发展新型角膜组织缺损修复材料提供基础。

胶原作为角膜基质的主要成分，拥有着良好的生物相容性，是理想的角膜修复材料。我们通过不同的制备工艺，制备出了具有层状结构的不同成分与功能的胶原基角膜修复材料，并实现了抗菌功能，抗菌药物缓释可达一周以上，并且其理化性能如光学性能、含水率、离子透过率、力学性能特别是耐手术线缝合性能都满足角膜修复材料的临床需求。体外细胞实验表明，这些材料均具有良好的生物相容性，角膜上皮细胞可以在其表面粘附与增殖并保持细胞正常的形态。动物实验结果表明，材料均具有良好的体内生物相容性并，可以快速完成上皮化并使角膜恢复透明与平整，体现出良好的组织修复效果。在成果转化方面，已建立产品标准和主要技术要求体系，且已初步建立了符合GMP管理规范的生产线与正在开展型式检验。