Investigating Corneal Biomechanics after Collagen Cross-linking

角膜是位于眼睛前部的透明圆顶状组织，允许光线进入眼睛。 角膜的机械性能在维持其稳定性和光学功能方面起着重要作用。由于诸如圆锥角膜和角膜扩张的眼科疾病导致的角膜结构完整性的丧失导致显著的隆起，并且可能导致严重的视力损害，包括失明。使用核黄素和紫外线A（UVA）光的角膜胶原交联是一种最近的治疗程序，其恢复角膜力学并阻止其形状的不规则变化的进展。然而，尽管有很好的实验和临床数据，其潜在的机制仍然未知。在这项研究中，一个综合的实验和计算框架将被用来表征胶原交联过程对角膜生物力学特性的不同方面的影响。 对这种微创手术的强化效果有更深入的基本理解，将导致其性能和有效性的显著提高。本项目将为角膜胶原交联治疗的潜在机制提供新的见解，并将评估其在恢复角膜机械强度方面的疗效。为此，将使用不同的体外实验技术来测量使用核黄素和UVA进行胶原交联后角膜组织的机械性质的变化。这些实验将由基于混合物理论的数值有限元模型进行补充。从力学的角度来看，角膜基质将被建模为由基质和增强胶原纤维组成的复合材料。除了该项目对现有角膜研究的重大贡献外，其成功完成将产生更广泛的影响，并可能最终导致新的工程设计概念。 最后，该项目还包括一些教育活动。这些努力的主要目标是吸引STEM领域的学生，并培养/吸引生物力学的本科生和研究生。预计这个项目，其生物学和力学的融合，将激励学生参与工程研究，帮助他们更好地理解科学，生物学和工程之间的联系。

The cornea is a transparent dome-shaped tissue at the front of the eye that allows light rays to enter the eye. The mechanical properties of the cornea play an important role in maintaining its stability and optical function. The loss of corneal structural integrity because of ophthalmic diseases such as keratoconus and ectasia leads to significant bulging and may cause severe visual impairment including blindness. Corneal collagen crosslinking using riboflavin and ultraviolet-A (UVA) light is a recent treatment procedure that restores corneal mechanics and halts the progression of irregular changes in its shape. Nevertheless, despite promising experimental and clinical data, its underlying mechanisms are still unknown. In this research, an integrated experimental and computational framework will be used to characterize the effects of the collagen crosslinking procedure on different aspects of corneal biomechanical properties. The deeper fundamental understanding of strengthening effects of this minimally invasive procedure could lead to significant improvement of its performance and effectiveness.This project will provide novel insight into the underlying mechanisms of corneal collagen crosslinking therapy and will assess its efficacy in restoring the mechanical strength of the cornea. To this end, different in vitro experimental techniques will be used to measure the changes in the mechanical properties of corneal tissue after collagen crosslinking using riboflavin and UVA. These experiments will be complemented by a numerical finite element model based on mixture theory. From the mechanics point of view, the corneal stroma will be modelled as a composite material consisting of a ground substance and reinforcing collagen fibrils. In addition to the significant contribution of this project to the existing body of research on the cornea, its successful completion will have a broader impact and may eventually lead to new engineering design concepts. Finally, this project includes a number of educational activities. The primary objectives of these efforts are to attract students in STEM fields and train/engage both undergraduate and graduate students in biomechanics. It is expected that this project, with its blend of biology and mechanics, will motivate students to participate in engineering research by helping them better appreciate the connection between science, biology, and engineering.