Tissue Engineering Cornea Replacements

描述（申请人提供）：角膜损伤会导致严重的视力下降，仅次于白内障。角膜置换术是一项发展中的技术，由于疾病（如疱疹感染）、LASIK并发症、遗传问题（如富氏病）和相关手术并发症（如白内障），对许多患者来说，角膜置换术正成为一种必需品。目前用于角膜移植的策略主要是使用合成材料或致敏材料。虽然这些策略部分有效，但缺点是它们会刺激宿主免疫反应，导致组织排斥或携带疾病从不健康的供体器官转移的风险。越来越多的眼科矫正手术使角膜不适合移植，进一步减少了可接受的过敏性供应，使这些并发症更加复杂。人类角膜替代物的发展，以减轻这些缺点是迫切需要的，这是拟议计划的目标。假设丝蛋白-生物材料板层系统与角膜特异性细胞结合可以通过生物工程来匹配体内角膜特性并满足功能要求。该系统将利用丝绸的新材料和生物特性，包括表面微图案来引导细胞和细胞外基质沉积，缓慢降解，生物相容性，光学透明度和机械耐久性，用于处理，缝合和耐受眼压。一种缓慢降解的角膜组织系统，允许宿主原生组织替代，将为角膜移植技术提供重要的新进展。结合角膜干细胞，我们期望优化细胞-丝相互作用首先在二维，然后作为三维板层结构。随后将对这些角膜组织系统（机械、光学）的性能进行功能评估，并优化手术方法和宿主整合。该计划的结果将是人类角膜替代物的体外优化和效用的体内评估。研究团队拥有支持项目计划所需的材料、细胞和研究系统的背景，并且在我们的R21项目中收集的数据为拟议研究的各个方面提供了支持文件。我们解决这一需求的方法是独特的，并提供新颖的方法来满足日益增长的角膜替代需求。体外来源的成功开发将改善目前的短缺，并为患者提供急需的替代方案。

DESCRIPTION (provided by applicant): Corneal damage causes significant vision loss, second only to cataracts. Corneal replacement is a developing technology that is becoming a necessity for many patients due to disease (e.g., herpes infection), complications from LASIK, hereditary problems (e.g., Fuch's disease) and complications from related surgeries (e.g., cataracts). Current strategies employed for corneal grafting primarily make use of synthetic or allergenic materials. While these strategies are partially effective, the downside is that they can stimulate host immune responses resulting in tissue rejection or carry the risk of transferring diseases from unhealthy donor organs. These complications are compounded by the growing use of corrective eye surgery which renders corneas unsuitable for grafting, further reducing the availability of acceptable allergenic supplies. The development of a human cornea replacement that alleviates these shortcomings is urgently needed and this is the goal of the proposed program. The hypothesis is that silk protein-biomaterial lamellar systems coupled with cornea- specific cells can be bioengineered to match in vivo corneal properties and meet functional requirements. The proposed system will exploit the novel material and biological features of silk, including surface micropatterning to guide cells and extracellular matrix deposition, slow degradation, biocompatibility, optical transparency and mechanical durability for handling, suturing and tolerating ocular pressures. A cornea tissue system that slowly degrades to allow for host native tissue replacement would offer a significant and novel advancement in corneal transplantation technology. In combination with corneal derived stem cells, we anticipate optimizing cell-silk interactions first in 2D and then as 3D lamellar structures. Functional assessments of the performance of these cornea tissue systems (mechanical, optical) will follow as will optimization of surgical methods and host integration. The outcome of the proposed program will be the in vitro optimization of human cornea replacements and in vivo assessments of utility. The research team has the required background with the materials, cells and systems of study to support the program plans, and the data collected during our R21 program provides supporting documentation for all aspects of the proposed study. Our approach to addressing this need is unique and offers novel methodology to meet the ever-growing demands for corneal replacements. Successful development of an in vitro source will ameliorate the current shortages and provide a much-needed alternative for patients. PUBLIC HEALTH RELEVANCE: Corneal diseases are responsible for extensive vision loss throughout the world, second only to cataracts. A number of sources are currently available for cornea replacement and include allergenic and synthetic materials. However, each of these options has problems, including disease transmission; inflammatory responses post implantation and poor material performance that may result in tissue rejection or device failure. These concerns are compounded by the growing demand for corrective surgery which renders would-be donor corneas unsuitable for grafting. Thus, a crucial need exists to develop new cornea replacement devices that provide the required material and biological properties to address the above limitations, while also offering an integration strategy that allows the device to be replaced by the patients' native tissues.