A Method to Generate Artificial Cornea Constructs

描述(由申请人提供)：组织工程学已经制造出临床上成功的相当于人类皮肤的东西(Integra)。类似的努力应用于角膜，一种无血管和相对无细胞的结缔组织，也应该会产生有益的结果。尽管已经生产了两种角膜结构，但它们在短期内用于临床的希望微乎其微，甚至作为临时支架也是如此。问题在于简单但高度组织的基质的复制。角膜入射光线、提供力量和产生光滑球面的能力关键取决于其纳米级的结构。在这个第一阶段的提案中，特殊目标1描述了一种新型胶原反应器的设计，该反应器能够生产排列整齐的胶原原纤维薄片。该系统基于定义明确的旋涂科学，旨在创造一个促进极薄薄片中胶原蛋白生成的微环境。在特定的目标2中，稍微修改一下，就可以将这些排列的纤维垂直堆叠起来，模仿原始的角膜基质。具体目标3建议通过将人类上皮和内皮细胞培养到工程基质上来创建基本的三层角膜结构。这种专注于基质的努力，对于最终产生适合用于角膜修复或替代疗法的生物材料至关重要。 拟议的商业应用：美国每年进行4万至5万例角膜置换手术，获取供体角膜的平均成本在1000美元至2000美元之间，市场规模为1亿美元。随着欧洲和第三世界市场更多地依赖美国的眼库，人口结构的变化限制了捐赠者池，以及角膜屈光手术变得更加普遍，捐赠者短缺预计将在未来加剧。人工角膜的市场是存在的，特别是一种可以潜在地与患者自己的细胞进行电镀的人工角膜，这将减少器官排斥的机会。

DESCRIPTION (provided by applicant): Tissue engineering has produced a clinically successful equivalent of human skin (Integra). Similar efforts, applied to the cornea, an avascular and relatively acellular connective tissue, should also yield beneficial results. Although two corneal constructs have been produced, there is little hope of their use in the clinic in the near term, even as temporary scaffolding. The problem lies in the reproduction of the simple but highly organized stroma. The ability of the cornea to admit light, provide strength and generate a smooth spherical surface depends critically on its nanoscale structure. In this Phase I proposal, specific aim 1 describes the design of a novel collagen reactor capable of producing thin sheets of aligned collagen fibrils. The system is based on the well-defined science of spin coating and is designed to create a microenvironment promoting collagen tibrillogenesis in extremely thin sheets. In specific aim 2, a slight modification allows the orthogonal stacking of these sheets of aligned fibrils, mimicking the primary corneal stroma. Specific aim 3 proposes to create a rudimentary three-layered corneal construct by culturing human epithelium and endothelium onto the engineered stroma. Such an effort, focused on the stroma, is critical to the eventual generation of a biomaterial suitable for use in corneal repair or replacement therapy. PROPOSED COMMERCIAL APPLICATION: Between 40,000 and 50,000 cornea replacement surgeries are performerd in the United States every year, with an average cost of harvesting donor corneas ranging between $1,000-$2,000, yielding a market of $100M. Donor shortages are expected to grow in the future, as European and third world markets depend more on US-based eye banks, demographic changes limit donor pools, and keratorefractive surgery becomes more prevalent. A market exists for an artificial cornea, particularly one that can potentially be plated with a patient's own cells, which will reduce the chances of organ rejection.