SBIR Phase I: Corneal Tissue Scaffold Using Synthetic Nonwoven Matrices

这份小型企业创新研究第一阶段的意见书建议设计和生产基于纳米纤维的角膜组织支架，以治疗角膜疾病，角膜疾病是全球第二大最常见的致盲原因，影响着1000-1500万人。这一创新方法使用了生物兼容聚合物的电纺垫，将对其机械和光学性能进行表征。候选垫子将使用独特的聚丙烯酸化学进行功能化，将细胞外基质蛋白质层粘连蛋白和纤维连接蛋白连接到高孔、高表面积的纳米纤维垫上。然后，垫子将被消毒，与培养的人角膜缘干细胞种植，并通过层粘连蛋白和纤维连接蛋白配体连接到支架上。将对细胞活性和粘附性进行研究，以确定植入眼内的最佳透明、生物兼容、无病原体的角膜支架。这项研究的更广泛影响包括其他眼移植需求，如角膜内皮细胞和视网膜色素上皮细胞移植(用于黄斑变性)，以及几乎所有身体组织的组织工程，从心脏瓣膜叶到肌腱修复。较新的部分角膜移植手术，如快速发展的后人S剥离内皮角膜移植(DSEK)，也将类似地受益于种植了人内皮细胞的透明组织支架。在世界范围内，对健康捐献组织的需求远远超过了可用的供应。全球角膜移植市场每年超过220亿美元。从眼部生物工程中获得的经验将转化为在纳米纤维支架上定制其他干细胞，用于人体不同领域的应用，扩大这项技术对老龄化人口的影响。

This Small Business Innovation Research Phase I submission proposes to design and produce nanofiber-based corneal tissue scaffolds to treat corneal diseases, the second most common cause of blindness worldwide, affecting 10-15 million people. This innovative approach uses electrospun mats from biocompatible polymers, which will be characterized for mechanical and optical properties. Candidate mats will be functionalized using a unique poly(acrylic) acid chemistry, conjugating extracellular matrix proteins laminin and fibronectin to the highly porous, high surface area nanofiber mats. Mats will then be sterilized, seeded with cultured human limbal stem cells, and attached to the scaffolds via laminin and fibronectin protein ligands. Cell viability and adhesion will be studied to determine the optimal transparent, biocompatible, pathogen-free, corneal scaffold for implantation in the eye. The broader impacts of this research include other ocular transplantation needs, such as corneal endothelial cell and retinal pigment epithelial cell transplantation (for macular degeneration), as well as tissue engineering for virtually all body tissues, from cardiac valve leaflets to tendon repair. Newer partial keratoplasty procedures, such as the rapidly evolving Descemet?s stripping endothelial keratoplasty (DSEK), would similarly benefit from a transparent tissue scaffold seeded with human endothelial cells. Worldwide, the need for healthy donor tissues far exceeds the available supply. This corneal transplant market is in excess of $22 billion annually worldwide. Experience gained from ocular bioengineering will translate into customization of other stem cells on nanofiber scaffolds for applications in diverse areas of the human body, broadening the impact of this technology for an aging population.