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Nanostructured Porous Silicon / Polymer Composites as Ophthalmic Implants

纳米结构多孔硅/聚合物复合材料作为眼科植入物

基本信息

批准号：
8549255
负责人：
JEFFERY L COFFER
金额：
$ 14.37万
依托单位：
TEXAS CHRISTIAN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-30 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8549255
关键词：
Address Adult Affect Allogenic Anterior eyeball segment structure Autologous Blindness Cell-Matrix Junction Cells Chemicals Chemistry Cornea Cytology DNA Debridement Disease Dyes Environment Epithelial Epithelial Cells Extracellular Matrix Eye Eye diseases Genomics Growth Growth Factor Histopathology Human Immune Implant Inbred Strain Inbred Strains Rats Inflammation Inflammatory Investigation Kinetics Location Mechanics Microscopy Modeling Oral mucous membrane structure Outcome Patients Phenotype Polymerase Chain Reaction Polymers Population Porosity Process Property Rattus Research Design Research Methodology Risk Route Shapes Silicon Staining method Stains Stem cells Structure Surface Testing Tissues Transplantation Variant adult stem cell base biomaterial compatibility caprolactone clinically relevant corneal epithelium effective therapy flexibility impression improved in vivo migration nanostructured novel ocular surface oxidation particle repaired research study scaffold soft tissue stem cell niche stemness

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of this project is to develop novel porous silicon-based ophthalmic implants as scaffolds for autologous cell transfer to the eye, for the treatment of human ocular surface disease. The proposed base component for such implants is nanostructured porous silicon in the form of microparticles. Porous silicon is a relatively non-toxic, completely biodegradable material that is easily prepared and modified, can be loaded efficiently with bioactives, shows excellent biocompatibility and supports the growth of mammalian ocular cells. The addition of a resorbable organic polymer component to the structure adds mechanical flexibility, ease of handling, and reduction of any possible deleterious effects based on shape of the porous silicon microparticles. Clinically relevant rat models of ocular surface disease will be used. This proposal addresses two specific aims: (1) to fabricate novel porous silicon/resorbable polymer composites, functionalize their surfaces, and load them with bioactive species, to generate supports for the transfer of expanded populations of rat oral mucosa-derived stem cells to the ocular surface, and to provide an artificial stem cell niche; and (2) to explore the potential of these implants carrying autologous cells to modulate ocular surface disease, following transfer to the eye of the rat in vivo. Research Design and Methods: (1) Composites of porous silicon microparticles and electrospun poly(¿-caprolactone) or other resorbable polymers will be fabricated, surface-derivatized, characterized, and loaded with bioactives such as soluble growth factors. The properties of these composite will be tuned by the composite structure but also by the properties of the porous silicon microparticles present. Variation of the porosity of the porous silicon component will alter the rate of silicon degradatio and lifetime of the matrix. Altering the surface chemistry will not only affect porous silicon degradation kinetics, but with judicious selection of appropriate biomolecules adsorbed on to the porous silicon will improve the attachment, survival and growth of epithelial cells. (2) Rat oral mucosal epithelial cells will be expanded on the composite materials and the differentiation status of cells examined by staining for phenotype specific markers. Ex vivo expanded populations or explants containing putative adult stem cells and transient amplifying cells will be transplanted to the rat ocular surface, to test their ability to repair a damaged ocular surface. Impression cytology of the central cornea followed by polymerase chain reaction will be used to detect donor cell genomic DNA on the ocular surface, and cell tracker dyes will be used to visualize migration of donor cells. The cell donors and recipient rats will be of the same inbred strain, so that no immunological rejection will occur.

描述（由申请人提供）：本项目的长期目标是开发新型多孔硅基眼科植入物，作为自体细胞转移至眼睛的支架，用于治疗人类眼表疾病。这种植入物的基础成分是微粒形式的纳米结构多孔硅。多孔硅是一种相对无毒、完全可生物降解的材料，易于制备和改性，可有效负载生物活性物质，显示出优异的生物相容性，并支持哺乳动物眼细胞的生长。将可再吸收的有机聚合物组分添加到结构中增加了机械柔性、易于处理，并且基于多孔硅微粒的形状减少了任何可能的有害影响。将使用眼表疾病的临床相关大鼠模型。本研究提出了两个具体目标：（1）制备新型多孔硅/可吸收聚合物复合材料，使其表面功能化，并负载生物活性物质，以产生用于将扩增的大鼠口腔粘膜来源的干细胞群转移到眼表面的支持物，并提供人工干细胞龛;和（2）探索这些携带自体细胞的植入物在体内转移到大鼠眼睛后调节眼表疾病的潜力。研究设计和方法：（1）多孔硅微粒和电纺聚（ε-己内酯）或其它可再吸收聚合物的复合物将被制造、表面衍生化、表征并负载生物活性剂如可溶性生长因子。这些复合材料的性质将通过复合材料结构以及存在的多孔硅微粒的性质来调节。多孔硅组分的孔隙率的变化将改变硅降解的速率和基质的寿命。改变表面化学不仅会影响多孔硅降解动力学，而且明智地选择吸附在多孔硅上的适当生物分子将改善上皮细胞的附着、存活和生长。(2)将大鼠口腔粘膜上皮细胞在复合材料上扩增，并通过表型特异性标记物染色检查细胞的分化状态。含有推定的成体干细胞和瞬时扩增细胞的离体扩增的群体或外植体将在体外培养。移植到大鼠眼表，以测试它们修复受损眼表的能力。将使用中央角膜的印模细胞学检查，然后进行聚合酶链反应，以检测眼表上的供体细胞基因组DNA，并使用细胞追踪染料观察供体细胞的迁移。细胞供体和受体大鼠将是相同的近交系，因此不会发生免疫排斥反应。