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）：人造角膜有潜力使全世界数百万因角膜疾病而失明的人受益。虽然角膜假体已经以各种形式出现了许多年，但它们的广泛应用受到其不透明或挤压的倾向的限制。本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和支持表面上皮化和外周组织整合，提高其体内稳定性。我们假设，针对特定部位细胞生长而设计的内在蛋白抗性材料将构成可持续人工角膜的基础。提出的工作是对一种创新的、光刻制造的结构进行综合评估，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的聚乙二醇/聚丙烯酸（PEG/PAA）双网络“核心”光学组件，它将支持表面上皮化，但抵抗大量蛋白质吸附，以及一个互穿的微图案聚丙烯酸羟乙酯（PHEA）“裙”，它将促进强大的基质组织整合。这种设计策略很有吸引力，因为1)PEG/PAA是一种优秀的中心光学材料，由于其独特的透明度、强度、渗透性和抗蛋白质吸附的组合，2)PHEA是一种亲水性、细胞相容性和快速光聚合的网络，可以以高保真度绘制图案，并可以与PEG和PAA相互渗透。3)光刻技术可用于在这些水凝胶中以微米级精度促进部位特异性表面上皮化和大块组织整合。结合原型材料的力学和分子/细胞界面特性的体外和体内评估，具体目标是：1。通过动态力学分析、蛋白质吸附实验和活体角膜植入等研究人工角膜材料的生物力学和界面特性。2. 通过体外测量表面生物活性、细胞迁移和粘附以及体内上皮化研究，表征和控制PEG/PAA中心光学表面上皮化。3. 通过评估光刻图案、微穿孔水凝胶阵列的体外和体内基质伤口愈合情况，确定最佳基质组织整合的裙边设计。