New Biomaterials for Cornea Replacement

用于角膜置换的新型生物材料

• 批准号: 7527689
• 负责人: DAVID L. KAPLAN
• 金额: $ 19.1万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7527689
• 关键词: Address; Affect; Allogenic; Animals; Architecture; Area; Biochemical; Biocompatible; Biocompatible Materials; Biological; Biological Assay; Biological Models; Biomedical Engineering; Blindness; Cataract; Cell Adhesion; Cell Communication; Cell Density; Cell Survival; Cell physiology; Cells; Cellular Morphology; Cellular biology; Cicatrix; Collaborations; Collagen Fibril; Cornea; Corneal Diseases; Cultured Cells; Data; Deposition; Devices; Disease; Endothelial Cells; Engineering; Epithelial; Equipment Malfunction; Exploratory/Developmental Grant; Extracellular Matrix; Fibroblasts; Fibroins; Film; Fostering; Foundations; Goals; Grant; Human; Immune response; Immunohistochemistry; In Situ; In Vitro; Infection; Inherited; Keratoplasty; Laboratories; Laser In Situ Keratomileusis; Mechanics; Metabolic; Methods; Modeling; Morphology; Numbers; Operative Surgical Procedures; Ophthalmologic Surgical Procedures; Optics; Organ Donor; Oryctolagus cuniculus; Outcome; Patients; Perforation; Performance; Phase; Population; Process; Property; Proteins; Public Health; Replacement Therapy; Research; Rest; Silk; Solid; Spectroscopy, Fourier Transform Infrared; Standards of Weights and Measures; Structure; Surgical sutures; System; Techniques; Technology; Tissue Engineering; Tissue Model; Tissues; Transmission Electron Microscopy; Transplantation; Transplanted tissue; Variant; analytical tool; base; biomaterial compatibility; cell growth; cell type; concept; density; design; design and construction; disease transmission; experience; implantation; nanoscale; novel; pressure; protein expression; response

DESCRIPTION (provided by applicant): Corneal damage causes significant vision loss in the general world population, second only to cataracts. Corneal replacement is a developing technology that is rapidly becoming a necessity for many patients. Many of the reasons for corneal replacement therapies include scarring from disease (e.g. herpes infection) or complications from LASIK; hereditary problems (e.g., Fuch's disease) and complications from other surgeries (e.g., cataracts). Current strategies employed for corneal grafting make use of allogenic or synthetic materials. These strategies are only partially effective, however, and may stimulate host immune responses that result in tissue rejection. In addition, there is the potential for transfer of diseases from unhealthy donor organs. These issues are compounded by the growing use of corrective eye surgery which renders corneas unsuitable for grafting which will further impact the availability of acceptable allogenic supplies. A cornea replacement that alleviates these issues would be a clinically important advance, and this is the goal of the present exploratory proposal (R21). The hypothesis is that a unique protein-biomaterial system based on silk fibroin can be bioengineered to match cornea functional requirements in combination with cornea-specific cells, to thus serve as a cornea replacement. The proposed system will exploit the novel material features of silk fibroin that include: slow degradation, biocompatibility, full optical transparency and mechanical durability for handling, suturing and ocular pressure requirements. The research team has the required background with silk material designs to meet the material performance requirements and the experience with the cornea cell biology to characterize the material-cell interactions outlined in this project. We will: (Aim #1) prepare and characterize the required protein films and assess cornea cell interactions (both rabbit and human) with these materials, and (Aim #2) assess a system concept that will mimic the native cornea in terms of a lamellar structure incorporating rabbit fibroblast, epithelial and endothelial cells with their appropriate extracellular matrix deposition. The outcome of this effort will be initial cornea designs to move forward into an R01 for animal studies related to cornea replacements. An interdisciplinary team has been assembled to meet the challenges and all of the required analytical tools are in place to address the experimental scope. A cornea tissue system that slowly degrades to allow for host native tissue replacement would offer a significant advancement in corneal transplantation technology. An R21 mechanism is proposed as this is a new exploratory initiative, building upon a solid foundation of prior research in both laboratories, but towards an entirely new tissue construct with new challenges and complexities. PUBLIC HEALTH RELEVANCE: Corneal damage causes significant vision loss in the general world population; it is second only to cataracts. There is a need to develop a readily available corneal tissue supply for transplantation in both the US and the rest of the world to meet the challenge of combating this prevalent form of vision loss. A unique protein-biomaterial system constructed from silk fibroin and cornea-specific cells can be bioengineered to serve as a total cornea replacement. The proposed system will exploit the novel biomaterial features of silk fibroin to produce a readily available supply of corneal tissue that will meet, or exceed, the biocompatibility and material properties of current allogenic transplant tissue.

描述（由申请人提供）：角膜损害在一般世界人口中造成严重的视力丧失，仅次于白内障。角膜替代是一种发展中的技术，它迅速成为许多患者的必要性。角膜替代疗法的许多原因包括疾病疤痕（例如疱疹感染）或Lasik并发症；遗传性问题（例如，富氏病）和其他手术（例如白内障）的并发症。角膜嫁接所采用的当前策略利用同种异体或合成材料。但是，这些策略仅是部分有效的，并且可能刺激导致组织排斥的宿主免疫反应。此外，还有从不健康的供体器官转移疾病的潜力。这些问题通过日益增长的矫正眼手术的使用使这些问题变得更加复杂，这使得不适合嫁接的角膜将进一步影响可接受的同种供应。缓解这些问题的角膜替代物将是临床上重要的进步，这是目前的探索性提议的目标（R21）。假设是，可以将基于丝绸纤维蛋白的独特蛋白质生物材料系统与角膜功能需求与角膜特异性细胞结合使用，从而作为角膜替代品匹配角膜功能需求。所提出的系统将利用丝绸纤维蛋白的新型材料特征，其中包括：缓慢降解，生物相容性，完全的光学透明度以及用于处理，缝合和眼压要求的机械耐用性。研究团队具有丝绸材料设计所需的背景，以满足材料性能要求以及角膜细胞生物学的体验，以表征该项目中概述的材料 - 细胞相互作用。我们将：（目标＃1）用这些材料准备和表征所需的蛋白质膜，并评估角膜细胞相互作用（兔子和人），（AIM＃2）评估一个系统概念，该概念将模仿本地角膜，该层状结构结合了兔成纤维成纤维细胞，上皮细胞，上皮细胞，其适当的外皮细胞胞外基质抑制作用。这项工作的结果将是最初的角膜设计，以向与角膜替换有关的动物研究前进。跨学科的团队已经组建了以应对挑战，并且所有必需的分析工具都适当解决实验范围。角膜组织系统缓慢降解以允许宿主本地组织置换，将在角膜移植技术方面取得显着进步。提出了一种R21机制，因为这是一项新的探索性计划，这是基于两个实验室先前研究的坚实基础，但要朝着具有新的挑战和复杂性的全新组织结构。公共卫生相关性：角膜损害导致一般世界人口的视力丧失；它仅次于白内障。有必要开发一种随时可用的角膜组织供应，以在美国和世界其他地区进行移植，以应对打击这种普遍的视力丧失形式的挑战。可以将由丝纤维蛋白和角膜特异性细胞构建的独特蛋白质生物材料系统进行生物工程，以作为总角膜替代品。所提出的系统将利用丝绸纤维蛋白的新型生物材料特征，生产出可用的角膜组织的供应，该组织将满足或超过当前同种异体移植组织的生物相容性和材料特性。