Quantitative measurement of mechanical properties in wound healing processes in a corneal stroma model by using vibrational optical coherence elastography (OCE)

Yilong Zhang,Zhihong Huang,Ying Yang,Yuting Ling,Duo Zhang,Chunhui Li,Mingkai Wang,Christine Purslow

doi:10.1364/boe.404096

Abstract

Corneal wound healing, caused by frequent traumatic injury to the cornea and increasing numbers of refractive surgeries, has become a vital clinical problem. In the cornea, wound healing is an extremely complicated process. However, little is known about how the biomechanical changes in wound healing response of the cornea. Collagen-based hydrogels incorporating corneal cells are suitable for replicating a three-dimensional (3D) equivalent of the cornea in-vitro. In this study, the mechanical properties of corneal stroma models were quantitatively monitored by a vibrational optical coherence elastography (OCE) system during continuous culture periods. Specifically, human corneal keratocytes were seeded at 5 × 105 cells/mL in the hydrogels with a collagen concentration of 3.0 mg/mL. The elastic modulus of the unwounded constructs increased from 2.950 ± 0.2 kPa to 11.0 ± 1.4 kPa, and the maximum thickness decreased from 1.034 ± 0.1 mm to 0.464 ± 0.09 mm during a 15-day culture period. Furthermore, a traumatic wound in the construct was introduced with a size of 500 µm. The elastic modulus of the neo-tissue in the wound area increased from 1.488 ± 0.4 kPa to 6.639 ± 0.3 kPa over 13 days. This study demonstrates that the vibrational OCE system is capable of quantitative monitoring the changes in mechanical properties of a corneal stroma wound model during continuous culture periods and improves our understanding on corneal wound healing processes.

Highlights

The cornea, as the outmost surface of the anterior eye, is responsible for approximately 2/3 of the total refractive power to focus light onto the retina for vision [1] and it acts as the major barrier for the eye from infectious agents [2]
The mechanical properties of corneal stroma models were quantitatively monitored by a vibrational optical coherence elastography (OCE) system during continuous culture periods
This study demonstrates that the vibrational OCE system is capable of quantitative monitoring the changes in mechanical properties of a corneal stroma wound model during continuous culture periods and improves our understanding on corneal wound healing processes

Summary

Introduction

The cornea, as the outmost surface of the anterior eye, is responsible for approximately 2/3 of the total refractive power to focus light onto the retina for vision [1] and it acts as the major barrier for the eye from infectious agents [2]. Corneal wound healing, caused by frequent traumatic injury to the cornea and increasing numbers of refractive surgeries, become a vital clinical problem [3]. When chemical or physical injuries occur on the cornea, scarring will form [4]. Untreated eye injuries or improper treatment can lead to disrupted vision and increasing risk of bacterial infections, causing severe damage to the cornea and even permanent vision loss [5]. Current clinical treatments for corneal injuries, are usually through topical antibiotics to minimise pain and infection, rather than focusing on the wound healing process, which may have no effect on or delay wound healing [6]. Corneal wound healing is an important clinical issue, but there is a need to better understand the chemical and physical mechanism of cellular behaviour, in order to improve and accelerate the healing process

Methods

Results

Conclusion