Engineering biomimetic corneal constructs

工程仿生角膜结构

• 批准号: 7123606
• 负责人: Jeffrey W Ruberti
• 金额: $ 14万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123606
• 关键词: Engineering; biomimetic; corneal; constructs

DESCRIPTION (provided by applicant): Every year in the United States, over 45000 corneal transplants are performed. The success rate for this procedure, owing to the relatively modest immune response in corneal tissue, is fairly high (90% after two years). Currently, access to donor tissue is adequate, however, the quality of donor tissue varies significantly, affecting surgical outcomes. In addition, the proliferation of LASIK procedures, which disqualifies a cornea for transplantation purposes, threatens to reduce the availability of donor corneas in the future. Finally, access to donor tissue elsewhere in the world, where there are over six million cases of corneal blindness, is severely limited. In recent years, laudable attempts have been made to produce corneal equivalents by tissue engineering. These constructs have proven the concept that three layers of cells, resembling the epithelium, keratocytes and endothelium may be cultured onto and within a collagen matrix for extended periods. However, such constructs cannot be used in the clinic primarily because the stromal matrix, which provides the cornea with mechanical strength and transparency cannot be reproduced, This proposal takes a stromal centric approach to generation of an artificial corneal construct. The corneal stroma comprises multiple layers (lamellae) of aligned 35 nm collagen fibrils stacked one upon another with fiber orientation rotating 90 degrees in each successive lamella. Recently, using microfluidics methods, artificial de novo "lamellae" have been generated by self-assembling collagen fibrils on a surface over which there is an extremely thin flowing film of collagen monomers. Using this technique alone or as a template for tissue engineering, the generation of a suitable stromal scaffolding for use in corneal repair or replacement, will be attempted. The first approach proposes to generate a stromal scaffolding by stacking many artificially generated, de novo "lamellae" orthogonally to one another to produce a thick stromal construct. The second approach uses a few of these de novo lamellae to influence, through contact guidance, the structure of matrix produced by ascorbic acid stimulated corneal fibroblasts. Following generation of thick stromal scaffolds by each method, epithelium and endothelium will be cultured on to the engineered stroma to produce an artificial cornea. The two constructs will be tested to determine their potential utility as corneal replacements.

描述（申请人提供）：在美国，每年有超过45000例角膜移植手术。由于角膜组织的免疫反应相对温和，这种手术的成功率相当高（两年后达到90%）。目前，供体组织的获取是充分的，然而，供体组织的质量差异很大，影响手术结果。此外，LASIK手术的普及，使角膜不符合移植目的，可能会减少未来角膜供体的可用性。最后，在世界其他地方，有超过600万例角膜失明，获得捐赠组织的机会受到严重限制。