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: 7872896
• 负责人: CHRISTOPHER N TA
• 金额: $ 45.65万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7872896
• 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; 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; 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; 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); prototype; regenerative; repaired; research clinical testing; response; restoration; scaffold; 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）：人工角膜有可能使全球数百万因角膜疾病而失明的人受益。尽管角膜假体已经以各种形式存在多年，但是它们的广泛应用受到其不透明或挤出倾向的限制。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形成和外周组织整合来改善体内稳定性。我们假设，已经被工程化用于位点特异性细胞生长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，血管造影制造的结构，专门设计，以解决目前的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“核心”的光学组件，将支持表面上皮化，但抵抗大量的蛋白质吸附，和一个互穿的，微图案化的聚（丙烯酸羟乙酯）（PHEA）的“裙子”，将促进强大的基质组织整合。这种设计策略是有吸引力的，因为1）PEG/PAA由于其透明度、强度、渗透性和对蛋白质吸附的抗性的独特组合而成为用于中央光学器件的优异材料，2）PHEA是亲水性、细胞相容性和快速光聚合网络，其可以高保真度图案化并且可以与PEG和PAA互穿，和3）可使用微电泳技术以微米级精度促进这些水凝胶内的位点特异性表面上皮形成和大量组织整合。结合原型材料的机械和分子/细胞界面特性的体外和体内评估，具体目的是：1.通过动态力学分析、蛋白质吸附试验和体内角膜植入，阐明人工角膜组件材料的生物力学和界面特性。2.通过表面生物活性、细胞迁移和粘附的体外测量以及体内上皮形成研究，表征和控制PEG/PAA中央光学器件上的表面上皮形成。3.通过评价血管造影图案化微穿孔水凝胶阵列内的体外和体内基质伤口愈合，确定最佳基质组织整合的裙缘设计。

项目成果

Interpenetrating polymer network hydrogel scaffolds for artificial cornea periphery.

用于人工角膜周边的互穿聚合物网络水凝胶支架。

• DOI: 10.1007/s10856-015-5442-2
• 发表时间: 2015
• 期刊: Journal of materials science. Materials in medicine
• 作者: Parke-Houben,Rachel;Fox,CourtneyH;Zheng,LuoLuo;Waters,DaleJ;Cochran,JenniferR;Ta,ChristopherN;Frank,CurtisW
• 通讯作者: Frank,CurtisW

Bioactive interpenetrating polymer network hydrogels that support corneal epithelial wound healing.

支持角膜上皮伤口愈合的生物活性互穿聚合物网络水凝胶。

• DOI: 10.1002/jbm.a.32056
• 发表时间: 2009
• 期刊: Journal of biomedical materials research. Part A
• 作者: Myung,David;Farooqui,Nabeel;Zheng,LuoLuo;Koh,Wongun;Gupta,Sarita;Bakri,Amit;Noolandi,Jaan;Cochran,JenniferR;Frank,CurtisW;Ta,ChristopherN
• 通讯作者: Ta,ChristopherN

Hindered Diffusion of Oligosaccharides in High Strength Poly(ethylene glycol)/Poly(acrylic acid) Interpenetrating Network Hydrogels: Hydrodynamic Versus Obstruction Models.

• DOI: 10.1016/j.polymer.2009.05.034
• 发表时间: 2009-12-10
• 期刊: POLYMER
• 影响因子: 4.6
• 作者: Waters, Dale J.;Frank, Curtis W.
• 通讯作者: Frank, Curtis W.

Morphology of Photopolymerized End-linked Poly(ethylene glycol) Hydrogels by Small Angle X-ray Scattering.

• DOI: 10.1021/ma101070s
• 发表时间: 2010-08-24
• 期刊: Macromolecules
• 影响因子: 5.5
• 作者: Waters DJ;Engberg K;Parke-Houben R;Hartmann L;Ta CN;Toney MF;Frank CW
• 通讯作者: Frank CW

Biocompatibility of poly(ethylene glycol) and poly(acrylic acid) interpenetrating network hydrogel by intrastromal implantation in rabbit cornea.

兔角膜基质内植入聚乙二醇和聚丙烯酸互穿网络水凝胶的生物相容性。

• DOI: 10.1002/jbm.a.35453
• 发表时间: 2015
• 期刊: Journal of biomedical materials research. Part A
• 作者: Zheng,LuoLuo;Vanchinathan,Vijay;Dalal,Roopa;Noolandi,Jaan;Waters,DaleJ;Hartmann,Laura;Cochran,JenniferR;Frank,CurtisW;Yu,CharlesQ;Ta,ChristopherN
• 通讯作者: Ta,ChristopherN