Tissue Engineering Cornea Replacements

描述（由申请人提供）：对人类角膜等效组织的需求持续增长，全球估计有1000万人患有角膜视力丧失。目前，满足这些日益增长的需求的临床选择很少。在这项更新提案中，我们将建立在我们在产生功能性人类角膜替代品方面的进展基础上。假设是基于机械上坚固的、图案化的、多孔的、薄的光学透明丝蛋白膜的组织工程化角膜系统与适当的细胞类型组合，可以产生功能性角膜组织等同物以满足这些临床需求。我们目前的数据支持计划的方法，并且还允许这些新的角膜组织系统对体内临床目标以及用于药物筛选的体外组织等效物产生更广泛的影响。我们计划扩大我们迄今为止的进展，并产生多功能的角膜组织系统，具有调整的组织重塑率，神经支配指导，植入后的规避以及局部感染和炎症的调节。进一步，我们计划建立这些角膜组织系统，以满足临床需要以及体外替代药物筛选。这些目标将致力于优化构成我们角膜设计基础的层状生物材料结构的结构和功能（重点关注重塑速率、感染和炎症的控制、特设细胞基质和优化的共培养方法，以开发基于角膜干细胞、上皮细胞和神经元细胞的部分厚度等效组织），持续组织功能的体外研究，以筛选眼部药物，以及体内研究，以评估临床相关性，从而进展到组织等同物的完全整合。参与本提案的跨学科研究人员团队将在本次更新中追求新的项目目标，包括大卫卡普兰（丝生物材料，组织工程角膜），詹姆斯Funderburgh（角膜组织生物学，角膜干细胞）和马克罗森布拉特（临床，动物模型）。

DESCRIPTION (provided by applicant): The need for human cornea equivalent tissues continues to grow with an estimated 10 million people worldwide suffering from corneal vision loss. There remain few clinical options today to meet these growing needs. In this renewal proposal we will build upon our progress in generating functional human cornea replacements. The hypothesis is that tissue engineered cornea systems based on mechanically robust, patterned, porous, thin optically clear silk protein films, in combination with appropriate cell types, can generate functional cornea tissue equivalents to meet these clinical needs. Our current data support the approaches planned and also allow for broader impact for these new cornea tissues systems for both in vivo clinical goals as well as for in vitro tissue equivalents fr drug screening. We plan to expand on our progress to date and generate multifunctional corneal tissue systems with tuned rates of tissue remodeling, innervation guidance, circumvention of suturing upon implantation and modulation of local infections and inflammation. Further, we plan to establish these corneal tissue systems to meet clinical needs as well as for in vitro substitute for drug screening. The aims will address optimizing the structure and function of the lamellar biomaterial structures that form the basis of our cornea designs (focusing on remodeling rates, control of infections and inflammation, ad hoc cell substrate, and optimized co-culture methods to develop partial thickness equivalent tissues based on corneal stem cells, epithelial, and neuronal cells), in vitro studies for sustained tissue function to screen ocular drugs, as well as n vivo studies to asses clinical relevance in order to progress to full integration of the tissue equivalents, are planned. An interdisciplinary team of investigators that has been involved in the present proposal will pursue the new project goals in this renewal, including David Kaplan (silk biomaterials, tissue engineered cornea), James Funderburgh (corneal tissue biology, corneal stem cells), and Mark Rosenblatt (clinical, animal models).