Artificial Cornea Based on Photolithographically Patterned, Biomimetic Hydrogels

基于光刻图案仿生水凝胶的人工角膜

• 批准号: 7498148
• 负责人: CHRISTOPHER N TA
• 金额: $ 9.5万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7498148
• 关键词: 2-hydroxyethyl methacrylate; Acrylates; Address; Adhesions; Adsorption; Affect; Amino Acids; Antibodies; Architecture; Area; Biocompatible Materials; Biological; Biological Assay; Biomechanics; Biomedical Engineering; Biomimetics; Caliber; Cell Adhesion; Cell Density; Cell Proliferation; Cell Survival; Cell-Cell Adhesion; Cells; Chemicals; Cicatrix; Clinical; Collagen; Collagen Type I; Color; Condition; Contact Lenses; Cornea; Corneal Diseases; Coupled; Crosslinker; Cues; D Cells; Data; Dental Inlays; Deposition; Development; Devices; Dimensions; Economics; Electrostatics; Engineering; Epithelial; Epithelial Cells; Ethylene Glycols; Evaluation; Event; Exhibits; Extracellular Matrix; Eye; Fibroblasts; Film; Friction; Glass; Goals; Harvest; Health; Heating; Histologic; Human; Hydrogels; Hydrogen Bonding; Immunohistochemistry; Implant; In Vitro; Infection; Investigation; Keratoplasty; Kinetics; Laboratories; Lamellar Keratoplasty; Life; Measurement; Measures; Mechanics; Metabolic; Microscopy; Modification; Molecular; Molecular Conformation; Monitor; Morphology; Myofibroblast; Nutrient; One-Step dentin bonding system; Optics; Oryctolagus cuniculus; Pattern; Peripheral; Permeability; Phenotype; Physiological; Polyhydroxyethyl Methacrylate; Principal Investigator; Process; Property; Prosthesis; Protein Analysis; Protein Binding; Proteins; Quartz; Relative (related person); Reporting; Research; Research Personnel; Resistance; Sampling; Silicon Dioxide; Site; Source; Spectrum Analysis; Staining method; Stains; Structure; Supporting Cell; Surface; Techniques; Testing; Tissue Donors; Tissue Engineering; Tissues; Visually Impaired Persons; Weight-Bearing state; Work; Wound Healing; acrylate; acrylic acid; base; biomaterial compatibility; blind; calcification; cell growth; cell motility; citrate carrier; density; design; ethylene glycol; follow-up; hydrophilicity; implantation; improved; in vivo; indexing; innovation; interfacial; light microscopy; migration; next generation; photopolymerization; poly(2-hydroxyethyl acrylate); programs; prototype; repaired; research clinical testing; response; restoration; scaffold; size; wound

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.

人造角膜有可能使全世界数百万因角膜疾病失明的人受益。虽然 角膜！多年来，假肢已以各种形式出现，其广泛应用已 受到其不透明或挤压倾向的限制。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，产生具有改善体内稳定性的人造角膜 对表面上皮化和周围组织整合的吸附和支持。我们假设 为特定位点细胞生长而设计的本质上具有蛋白质抗性的材料将会形成 可持续人造角膜的基础。拟议的工作是对创新、 光刻制造的结构专门设计用于解决当前的主要缺陷 角膜假体。我们的设计由机械增强的聚（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体积 蛋白质吸附，以及互穿微图案聚（丙烯酸羟乙酯）（PHEA）“裙子” 将促进强健的基质组织整合。这种设计策略很有吸引力，因为 1) PEG/PAA 是一种 由于其透明度、强度、渗透性、 和对蛋白质吸附的抵抗力，2) PHEA 是一种亲水性、细胞相容性和快速 光聚合网络，可以高保真地图案化，并且可以与 PEG 互穿 PAA，和3)光刻技术可用于促进位点特异性表面上皮化和 这些水凝胶中的大量组织以微米级的精度整合。结合体外和体内 原型材料的机械和分子/细胞界面特性的评估， 具体目标是： 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、蛋白质吸附测定和体内角膜分析成分材料 植入。 2. 体外表征和控制 PEG/PAA 中心光学器件的表面上皮化 表面生物活性、细胞迁移和粘附的测量以及体内上皮化研究。 3. 通过评估体外和体内基质，确定最佳基质组织整合的裙子设计 光刻图案微穿孔水凝胶阵列内的伤口愈合。