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: 7210019
• 负责人: CHRISTOPHER N TA
• 金额: $ 47.65万
• 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/7210019
• 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

DESCRIPTION (provided by applicant): Artificial corneas have potential to benefit millions worldwide who are blind due to corneal disease. Although corneal 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 surface epithelialization 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 designed to address the 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(hydroxyethyl acrylate) (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.

描述(由申请人提供)：人工角膜有可能造福全球数百万因角膜疾病而失明的人。虽然角膜假体多年来一直以各种形式出现，但由于其混浊或突出的倾向，其广泛应用一直受到限制。这项研究的总体目标是开发下一代人工角膜，通过增强对蛋白质吸附的抵抗力以及对表面上皮化和周围组织整合的支持来提高体内稳定性。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构成可持续人工角膜的基础。这项拟议的工作是对一种创新的、采用光刻技术制造的结构的综合评估，该结构专门设计用于解决当前角膜假体的主要缺陷。我们的设计包括一个机械增强型聚乙二醇/聚丙烯酸(PEG/PAA)双网络“核心”光学组件，它将支持表面上皮化，但防止大量蛋白质吸附，以及一个相互穿透的微图案聚丙烯酸羟乙酯(PHEA)“裙子”，将促进强大的间质组织整合。这一设计策略之所以有吸引力，是因为1)由于其独特的透明度、强度、渗透性和抗蛋白质吸附能力，聚乙二醇胺/聚乙二醇胺是一种优秀的中央光学材料，2)PHEA是一种亲水性、细胞相容性和快速光聚合网络，可以高保真地构图，并且可以与聚乙二醇胺和聚乙二醇胺相互渗透，以及3)可以使用光刻技术以微米级的精度促进特定部位的表面上皮化和组织在这些水凝胶中的整合。结合体外和体内对原型材料的力学性能和分子/细胞界面性能的评价，具体目的是：1.通过动态力学分析、蛋白质吸附分析和体内角膜植入，阐明人工角膜组件材料的生物力学和界面性能。2.通过体外表面生物活性、细胞迁移和黏附的测定以及体内上皮化的研究，表征和控制聚乙二醇胺中心光学材料的表面上皮化。3.通过评估光刻图案化微穿孔水凝胶阵列中体外和体内基质伤口的愈合情况，确定最佳基质组织整合的裙子设计。