Characterising Viscoelastic Properties of Corneal Stromal Models with Optical Coherence Elastography

Abstract

The cornea, a transparent avascular tissue, is essential for human vision by accounting for approximately two-thirds optical power of the eye. Also, it plays as a structural barrier and protects the eye from infections. Corneal injuries or diseases are a leading cause of visual loss and even blindness. It is reported that 45 million people are affected by corneal blindness. The transplantation of a donor cornea to change the injured one is the gold standard treatment. However, a shortage of donors and a high probability of immune rejection are the primary reasons for establishing alternative tissue-engineered corneal equivalent models. Collagen scaffold is the most common material to replicate the native corneal stroma. However, there is limited knowledge on the influence of cell behaviours interaction with collagen matrix on the biomechanics of corneal stromal models.

This thesis developed tissue-engineered corneal stromal models by collagen-based hydrogels incorporated with human corneal stromal cells to mimic the injured or pathophysiological altered corneal extracellular matrix (ECM). The first study of this thesis aimed at characterising the mechanical property of neo-tissue in the wounded corneal stromal model during wound healing with vibrational optical coherence elastography (OCE). The cross-sectional elastic modulus map was reconstructed based on the local strain of the model induced by mono-frequency vibration. Results showed that an increase in the stiffness of neo-tissue during wound healing was non-invasively and continuously monitored and finally became the same as normal tissue on day 13.

In the next study, the viscoelastic properties of corneal stromal models were continuously investigated with air-pulse OCE over 11 days. These stromal models were fabricated with various initial collagen scaffold concentrations. An air-pulse OCE system was developed to induce and track the surface acoustic wave (SAW) on the surface of corneal stromal models. The viscoelastic parameters of stromal models were estimated by fitting the SAW phase velocity dispersion into a SAW dispersion model. The stromal models with lower initial collagen concentrations had a faster increase in viscoelastic parameters and higher values by the end of the culture period.

Finally, artificial niches in an in vitro polydimethylsiloxane (PDMS) substrate and limbal niches in ex vivo cadaveric tissue of donors aged from 4 to 96 years were visualised with spectral-domain optical coherence tomography (SD-OCT). Vibrational OCE was utilised to characterise the mechanical property of the artificial niche and limbal niche. The results showed that the dimensions and biomechanical parameters of the limbal niche were significantly correlated with age.

In conclusion, this thesis shows that the developed OCE techniques are able to non-invasively characterise and provide local elastic modulus of the tissue-engineered corneal stroma and donor limbal tissues. The findings of this thesis enhance our understanding of cell-matrix interactions in the cornea with two different pathophysiological conditions and also biomechanics of the limbal niche.

Date of Award	2022
Original language	English
Awarding Institution	University of Dundee
Supervisor	Zhihong Huang (Supervisor) & Chunhui Li (Supervisor)