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）：人造角膜有可能使全球因角膜疾病而盲目的数百万人受益。尽管角膜假肢已经以多种形式获得了多年，但它们的广泛应用受到其欺骗或挤出的倾向的限制。这项研究的总体目标是通过增强对蛋白质吸附的耐药性和对表面上皮化和外周组织整合的支持，从而发展下一代人造角膜，并改善体内稳定性。我们假设为特定地点细胞生长设计的本质上具有抗蛋白质的材料将构成可持续人造角膜的基础。拟议的工作是针对专门针对当前角膜假体的主要缺陷而设计的创新，光刻构造的综合评估。 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.这种设计策略很有吸引力，因为1）PEG/PAA是透明度，强度，强度，渗透性和对蛋白质吸附的耐药性的独特组合，是一种理想的材料，2）PHEA是一种亲水性，细胞增强的，细胞增强的，并且可以迅速与PETERIQUENT和PEG ATERATIES一起使用，并且可以迅速地促进PEG和PEG的技术，并可以促进PEG和PAAA，并在3中散布PEG和PAAA，并可以触发和Paaa，并在3个网络中构成33这些水凝胶中的位点特异性表面上皮化和块状组织整合，具有微观阶的精度。特定的目的是结合原型材料的机械和分子/细胞界面特性的原型材料的体内和体内评估，是：1。通过动态机械分析，蛋白质吸附鉴定和体内角膜毛层植入。 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来表征和控制PEG/PAA中心光学上的表面上皮化。 3。通过评估光刻图案化的，微孔孔的水凝胶阵列中的体外和体内基质伤口愈合来确定最佳基质组织整合的裙子设计。

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

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

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