Artificial Cornea Based on Photolithographically Patterned, Biomimetic Hydrogels

人工角膜有可能使全世界数百万因角膜疾病而失明的人受益。虽然 角膜！修复术已经以各种形式存在了许多年，它们的广泛应用 受到其不透明或挤出倾向的限制。这项研究的总体目标是开发下一个 通过增强对蛋白质的抗性产生具有改进的体内稳定性的人工角膜 吸附和支持表面上皮化和外周组织整合。我们假设 为特定位点细胞生长而设计的内在抗蛋白质材料将形成， 可持续人工角膜的基础拟议的工作是一个创新的综合评价， 专门设计用于解决当前 角膜假体我们的设计包括机械增强的聚（乙二醇）/聚（丙烯酸） (PEG/PAA）双网络“芯”光学组件，其将支持表面上皮化但抵抗体积 蛋白质吸附，以及一种互穿的微图案化聚（丙烯酸羟乙酯）（PHEA）“裙”， 将促进稳健的基质组织整合。这种设计策略是有吸引力的，因为1）PEG/PAA是一种 由于其独特的透明度、强度、渗透性 和抗蛋白质吸附，2）PHEA是一种亲水性、细胞相容性和快速的 - 可以高保真度图案化并且可以与PEG互穿的光聚合网络， PAA，和3）可使用微生物技术促进位点特异性表面上皮形成， 在这些水凝胶中以微米级的精度实现大体积组织整合。体内外结合 原型材料的机械和分子/细胞界面性质的评估， 具体目标是：1.人工角膜的生物力学和界面特性 通过动态力学分析、蛋白质吸附测定和体内角膜移植， 置入2.通过体外表征和控制PEG/PAA中央光学器件上的表面上皮化 表面生物活性、细胞迁移和粘附的测量，以及体内上皮形成研究。 3.通过评价体外和体内基质，确定最佳基质组织整合的裙缘设计 伤口愈合在微穿孔的水凝胶阵列内。

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.