Tissue Engineering Cornea Replacements

描述(由申请人提供)：随着全球估计有1000万人患有角膜视力丧失，对人体角膜等值组织的需求继续增长。今天，满足这些日益增长的需求的临床选择仍然很少。在这项更新建议中，我们将在产生功能性人类角膜替代物方面取得进展。假说是，基于机械坚固、有图案、多孔、薄且光学透明的丝蛋白薄膜的组织工程化角膜系统，与适当的细胞类型相结合，可以产生功能相当的角膜组织，以满足这些临床需求。我们目前的数据支持计划的方法，也允许这些新的角膜组织系统在体内临床目标以及药物筛选的体外组织等效物方面产生更广泛的影响。我们计划扩大目前的进展，开发多功能的角膜组织系统，具有组织重塑、神经引导、避免植入时缝合以及调节局部感染和炎症的速度。此外，我们计划建立这些角膜组织系统，以满足临床需要，以及作为药物筛选的体外替代品。这些目标将致力于优化构成我们角膜设计基础的板层生物材料结构的结构和功能(重点关注重建率、感染和炎症的控制、特设细胞底物，以及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)，计划进行持续组织功能的体外研究以筛选眼部药物，以及进行体内研究以评估临床相关性以促进组织等效物的完全整合。参与本提案的一个跨学科研究小组将在这次更新中追求新的项目目标，包括David Kaplan(丝绸生物材料、组织工程角膜)、James Funderburgh(角膜组织生物学、角膜干细胞)和Mark Rosenblatt(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).