Novel in vitro dynamic corneal model with online mechanical characterisation for pharmaceutical screening and tissue engineering applications

用于药物筛选和组织工程应用的具有在线机械表征的新型体外动态角膜模型

• 批准号: BB/F002866/1
• 负责人: Ying Yang
• 金额: $ 42.02万
• 依托单位: Keele University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF002866%2F1
• 关键词: Novel; vitro; dynamic; corneal; model

The rabbit eye is frequently used to test new drugs or new therapies for corneal disease. One example of such as disease is keratoconus where the mechanical properties change over time. Concerns over the use of animals for eye research has been growing but efforts to replace these experiments with adequate tissue models have been lacking. To reduce or eliminate the use of animal models for understanding the biology and treatment of corneal disease, more physiologically relevant in vitro models must be developed. One feature of the cornea which is directly linked to some disease conditions is the mechanical integrity of the corneal stroma or tissue. However, to date, none of the 3D tissue models are able to assess or utilise the mechanical properties of the cornea as an outcome measure of drug testing in vitro. In this proposal, we propose to develop a novel on-line characterisation tool for mechanical properties, which can monitor viable tissue construction over time in a non-destructive and on-line manner under sterile conditions. This set up is part of new developments involving the establishment of a bioreactor for corneal tissue models which facilitates growth over a prolonged culture period. This novel methodology enables the mechanical property of the in vitro tissue to be used as a biomarker. After successfully establishing the methodologies, we shall use this in vitro model for the screening of pharmaceutical drugs and new therapies for keratoconus. Efficacy of drugs in our 3D models will be compared with existing data using animal models. Efficacy will be defined as maintained or improved mechanical integrity.

兔眼经常用于测试角膜疾病的新药或新疗法。此类疾病的一个例子是圆锥角膜，其机械性能随时间变化。人们对使用动物进行眼部研究的担忧不断增加，但缺乏用适当的组织模型替代这些实验的努力。为了减少或消除使用动物模型来了解角膜疾病的生物学和治疗，必须开发更多生理相关的体外模型。与某些疾病直接相关的角膜特征之一是角膜基质或组织的机械完整性。然而，迄今为止，没有任何 3D 组织模型能够评估或利用角膜的机械特性作为体外药物测试的结果衡量标准。在本提案中，我们建议开发一种新型的机械性能在线表征工具，该工具可以在无菌条件下以非破坏性和在线方式随时间监测可行的组织结构。该装置是新发展的一部分，涉及建立角膜组织模型生物反应器，促进长期培养期间的生长。这种新颖的方法使得体外组织的机械特性能够用作生物标志物。成功建立方法论后，我们将利用该体外模型来筛选圆锥角膜的药物和新疗法。我们的 3D 模型中药物的功效将与使用动物模型的现有数据进行比较。功效将被定义为维持或改善的机械完整性。

项目成果

Portable nanofiber meshes dictate cell orientation throughout three-dimensional hydrogels.

• DOI: 10.1016/j.nano.2010.12.011
• 发表时间: 2011-04
• 期刊: Nanomedicine : nanotechnology, biology, and medicine
• 作者: Ying Yang;I. Wimpenny;M. Ahearne

Chemical and Topographical Effects on Cell Differentiation and Matrix Elasticity in a Corneal Stromal Layer Model

• DOI: 10.1002/adfm.201200655
• 发表时间: 2012-09
• 期刊: Advanced Functional Materials
• 影响因子: 19
• 作者: S. Wilson;I. Wimpenny;M. Ahearne;S. Rauz;A. E. El Haj;Ying Yang