Lei Miao, Zhang Shaohua, Zhou Hang, Wan Haoran, Lu Yi, Lin Shaoliang, Sun Jianguo, Qu Xue, Liu Changsheng
Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
Eye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
ACS Nano. 2022 Jul 26;16(7):10632-10646. doi: 10.1021/acsnano.2c02291. Epub 2022 Jul 8.
Corneal transplantation is an effective treatment for reconstructing injured corneas but is very limited due to insufficient donors, which has led to a growing demand for development of artificial corneal substitutes (ACSs). Collagen is a potential building block for ACS fabrication, whereas technically there are limited capabilities to control the collagen assembly for creating highly transparent collagen ACSs. Here, we report an electro-assembly technique to kinetically control collagen assembly on the nanoscale that allows the yielding collagen ACSs with structure determined superior optics. Structurally, the kinetically electro-assembled collagen (KEA-Col) is composed of partially aligned microfibrils (∼10 nm in diameter) with compacted lamellar organization. Optical analysis reveals that such microstructure is directly responsible for its optimal light transmittance by reducing light scattering. Moreover, this method allows the creation of complex three-dimensional geometries and thus is convenient to customize collagen ACSs with specific curvatures to meet refractive power requirements. Available properties (e.g., optics and mechanics) of cross-linked KEA-Cols were studied to meet the clinical requirement as ACSs, and tests further proved their beneficial characteristics of cell growth and migration. An study established a rabbit lamellar keratectomy corneal wound model and demonstrated the customized collagen ACSs can adapt to the defective cornea and support epithelial healing as well as stroma integration and reconstruction with lower immunoreaction compared with commercial xenografts, which suggests its promising application prospects. More broadly, this work illustrates the potential for enlisting electrical signals to mediate collagen's assembly and microstructure organization for specific structural functionalization for regenerative medicine.
角膜移植是重建受损角膜的有效治疗方法，但由于供体不足，其应用非常有限，这导致对人工角膜替代品（ACS）开发的需求不断增长。胶原蛋白是制造ACS的潜在构建材料，然而在技术上，控制胶原蛋白组装以制造高度透明的胶原蛋白ACS的能力有限。在此，我们报告一种电组装技术，可在纳米尺度上动态控制胶原蛋白组装，从而生产出具有结构确定的优异光学性能的胶原蛋白ACS。在结构上，动态电组装的胶原蛋白（KEA-Col）由部分排列的微原纤维（直径约10纳米）组成，具有紧密的层状结构。光学分析表明，这种微观结构通过减少光散射直接导致其最佳透光率。此外，该方法允许创建复杂的三维几何形状，因此便于定制具有特定曲率的胶原蛋白ACS，以满足屈光力要求。研究了交联KEA-Col的可用特性（如光学和力学性能）以满足作为ACS的临床要求，测试进一步证明了它们在细胞生长和迁移方面的有益特性。一项研究建立了兔板层角膜切除术角膜伤口模型，并证明定制的胶原蛋白ACS可以适应角膜缺损，支持上皮愈合以及基质整合和重建，与商业异种移植物相比免疫反应更低，这表明其具有广阔的应用前景。更广泛地说，这项工作说明了利用电信号介导胶原蛋白组装和微观结构组织以实现再生医学特定结构功能化的潜力。
