MODIFICATION OF CORNEAL TISSUE ENGINEERED SCAFFOLDS TO PROMOTE EPITHELIALIZATION

改良角膜组织工程支架以促进上皮化

• 批准号: 7381342
• 负责人: Huiguang Zhu
• 金额: $ 6.9万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381342
• 关键词: MODIFICATION; CORNEAL; TISSUE; ENGINEERED; SCAFFOLDS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Attempts to augment and replace the cornea with synthetic materials have met with limited succeass, primarily because these devices have been unable to support and maintain a normal stratified epithelium. The fundamental problem is that the host epithelial cells recognize the polymer surface as other than stroma or "self" and, therefore, a degree of foreign body response is present throughout the life of the implant. Although natural materials often have good biocompatibility, they lack the strength to support tissue regeneration and the ability to withstand the natural wound remodeling process. It is advantageous, therefore, to consider combination strategies for leveraging the advantages of synthetic and natural materials for tissue engineering applications. For corneal material construction, a minimum 2-layer microstructured scaffold is specifically required to separate the epithelial layer from the stromal cell layer. The central part of the scaffold material must support infiltration and growth of stromal cells, whereas the outer surface of the scaffold must allow the adhesion and maintenance of the epithelial layer. Extracellular matrix proteins (ECMPs) and peptides covalently tethered to the scaffold surfaces are also needed to enhance cell growth. We propose to integrate novel chemistry, micro/nanofabrication, and cell biology methods to first understand and then control corneal both epithelial and stromal cell-material interactions as a method to engineer an effective corneal replacement/augmentation material. Our specific aims are as follows: Specific Aim I: To develop and characterize 3-dimensional scaffolds of silicone hydrogels, collagen, and chitosan (and/or copolymers thereof), as the framework for an optimal corneal replacement/augmentation material. Specific Aim II: To increase optimal cellular response to the developed polymer scaffold materials by modifying their surfaces with tethered ECMPs and peptides using novel micro/nanofabrication techniques. Specific Aim III: To quantify and analyze the cellular response to the developed polymer scaffolds using primary rabbit epithelial and keratocyte cell culture and corneal organ culture.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。用合成材料增强和取代角膜的尝试取得了有限的成功，主要是因为这些设备无法支持和维持正常的复层上皮。根本的问题是，宿主上皮细胞将聚合物表面识别为不同于基质或“自身”的表面，因此，在植入物的整个生命周期中，存在一定程度的异物反应。虽然天然材料往往具有良好的生物相容性，但它们缺乏支持组织再生的强度和承受自然伤口重塑过程的能力。因此，考虑利用合成材料和天然材料的优点用于组织工程应用的组合策略是有利的。对于角膜材料的构建，至少需要两层微结构支架来分隔上皮层和基质细胞层。支架材料的中心部分必须支持基质细胞的渗透和生长，而支架的外表面必须允许上皮层的黏附和维护。细胞外基质蛋白(ECMP)和共价连接到支架表面的多肽也是促进细胞生长所必需的。我们建议将新的化学、微/纳米制造和细胞生物学方法结合起来，首先了解并控制角膜上皮细胞和基质细胞-材料的相互作用，作为设计有效的角膜替代/增强材料的方法。我们的具体目标如下：具体目标I：开发和表征有机硅水凝胶、胶原和壳聚糖(和/或它们的共聚物)的三维支架，作为理想的角膜替代/增强材料的框架。具体目标II：通过使用新的微/纳米制造技术，用拴系的ECMP和多肽来修饰其表面，从而提高对所开发的聚合物支架材料的最佳细胞响应。具体目的III：利用原代培养的兔上皮细胞和角质形成细胞以及角膜器官培养来量化和分析所开发的聚合物支架的细胞反应。