Artificial Cornea Based on Photolithographically Patterned, Biomimetic Hydrogels

人工角膜有可能造福全球数百万因角膜疾病而失明的人。虽然 眼角膜！假肢多年来一直以各种形式出现，它们的广泛应用 受到其不透明或突出的倾向的限制。这项研究的总体目标是开发下一代 通过增强对蛋白质的抵抗力来提高体内稳定性的人工角膜的生成 表面上皮化和外周组织整合的吸附和支持。我们假设 为特定部位的细胞生长而设计的固有的蛋白质抗性材料将形成 可持续人工角膜的基础。建议的工作是对一种创新的、 专门为解决电流的主要缺陷而设计的光刻制作结构 角膜假体。我们的设计由机械增强型聚乙二醇/聚丙烯酸组成。 (PEG/PAA)双网络“核心”光学组件，支持表面上皮化但抵抗块状 蛋白质吸附，以及相互穿透的、带有微图案的聚丙烯酸羟乙酯(PHEA)“裙子” 将促进强大的间质组织整合。这种设计策略很有吸引力，因为1)PEG/PAA是一种 由于其独特的透明性、强度、渗透性、 和抗蛋白质吸附，2)PHEA是一种亲水性、细胞相容性和快速 一种可高保真图案化、可与聚乙二醇组分互穿的光聚合网络 3)光刻技术可用于促进特定部位的表面上皮化和 这些水凝胶中的大量组织整合具有微米级的精度。体内外结合 评估原型材料的机械和分子/细胞界面特性， 具体目的是：1.阐明人工角膜的生物力学和界面特性 通过动态力学分析、蛋白质吸附分析和活体角膜的成分材料 植入。2.用体外方法表征和控制聚乙二醇胺中心光学材料的表面上皮化 表面生物活性、细胞迁移和黏附的测量，以及体内上皮化研究。 3.通过对体外和体内基质的评价，确定最佳基质组织整合的裙子设计。 在光刻图案化微穿孔水凝胶阵列中的伤口愈合。

Artificial corneas have potential to benefit millions worldwide who are blind due to corneal disease. Although cornea! prosthetics have been available for many years in various forms, their widespread application has been limited by their propensity to opacify or extrude. The overall goal of this research is to develop the next generation of artificial cornea with improved in vivo stability through enhanced resistance to protein adsorption and support for both surfaceepithelialization and peripheral tissue integration. We hypothesize that intrinsically protein-resistant materials that have been engineered for site-specific cell growth will form the basis of a sustainable artificial cornea. The proposed work is an integrated evaluation of an innovative, photolithographically fabricated construct specifically designedto addressthe major deficiencies of current corneal prostheses. Our design consists of a mechanically enhanced poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) double network "core" optic component that will support surface epithelialization but resist bulk protein adsorption, and an interpenetrating, micropatterned poly(hydroxyethylacrylate) (PHEA) "skirt" that will promote robust stromal tissue integration. This design strategy is attractive because 1) PEG/PAA is an excellent material for a central optic due to its unique combination of transparency, strength, permeability, and resistance to protein adsorption, 2) PHEA is a hydrophilic, cytocompatible, and rapidly photopolymerizing network that can be patterned with high fidelity and can interpenetrate with PEG and PAA, and 3) photolithographic techniques can be used to promote site-specific surface epithelialization and bulk tissue integration within these hydrogels with micron-order precision. Combining in vitro and in vivo assessments of the prototype materials' mechanical and molecular/cellular interfacial properties, the Specific Aims are to: 1. Elucidate the biomechanical and interfacial properties of artificial cornea component materials through dynamic mechanical analysis, protein adsorption assays, and in vivo corneal implantation. 2. Characterize and control surface epithelialization on PEG/PAA central optics by in vitro measurement of surface bioactivity, cell migration and adhesion, and in vivo epithelialization studies. 3. Determine the skirt design for optimal stromal tissue integration by evaluating in vitro and in vivo stromal wound healing within photolithographically patterned, microperforated hydrogel arrays.