A Method to Generate Artificial Cornea Constructs

描述（由申请人提供）：组织工程已在临床上成功产生了人体皮肤的等效物（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，也应该产生有益的结果。虽然已经生产了两种角膜结构，但在短期内将其用于临床的希望很小，即使是作为临时支架。问题在于简单但高度组织化的基质的再生产。角膜吸收光线、提供强度和产生光滑球形表面的能力关键取决于其纳米级结构。在该阶段I提案中，具体目标1描述了能够产生排列的胶原原纤维的薄片的新型胶原反应器的设计。该系统基于旋涂的明确科学，旨在创造一个微环境，促进极薄的胶原蛋白胫骨发生。在具体目标2中，轻微的修改允许这些对齐的原纤维片的正交堆叠，模仿原代角膜基质。具体目标3提出通过在工程化基质上培养人上皮和内皮来创建基本的三层角膜构建体。这种专注于基质的努力对于最终产生适用于角膜修复或替代治疗的生物材料至关重要。 拟定商业应用：在美国，每年进行40，000至50，000次角膜置换手术，收获供体角膜的平均成本在1，000至2，000美元之间，产生1亿美元的市场。 由于欧洲和第三世界市场更加依赖美国的眼库，人口结构的变化限制了供体库，角膜屈光手术变得更加普遍，预计未来供体短缺将加剧。 人造角膜是有市场的，特别是那种可以植入病人自身细胞的人造角膜，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.