Hyaluronic acid from ophthalmic viscosurgical devices interacting with biomimetic substrates

Abstract

Complex fluids are used in a variety of surgical procedures. In particular, cataract surgery widely uses viscoelastic fluids named Ophthalmic Viscosurgical Devices (OVDs), which contain high molecular weight polymers such as hyaluronic acid (HA). OVDs fulfil a dual role: maintaining volume in the anterior chamber and protecting the cellular structure from accidental damage. They are classified into two categories: cohesive OVDs have a higher viscosity at rest and are removed as a blob, whilst dispersive OVDs spread on the cells to act as a protective cushion.

The main surgical risk associated with OVDs occurs if they remain in the eye at the end of the operation. If not properly removed, they can obstruct the flow of aqueous humour through the trabecular mesh-work, which in turn increases the intraocular pressure. Although rheological characterisation of OVDs is routinely performed, their surface interaction with biological tissues has been less studied. In particular, the mechanics of polymer adsorption and subsequent desorption is of great interest to better understand the differences between the two classes of OVDs in the levels of protection they confer and their ease of removal during aspiration at the end of surgery.

In order to study adsorption, we used Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) and phase modulation ellipsometry. After a polymer layer had formed, we injected a rinsing solution to mimic the irrigation/aspiration device used by surgeons in cataract surgery and gain insight on the desorption process. In addition to gold-coated QCM-D sensors, we used sensors functionalised with mucin to better mimic the surface properties of corneal endothelial cells.

Adsorption and desorption of polyvinylpyrrolidone (PVP) was first investigated as a model system, as described in Chapter 3. In Chapter 4, the same approach was applied to HA from diluted OVD solutions Although the adsorption of cohesive and dispersive OVDs is comparable in the dilute and semi-dilute regimes, a difference emerges in the entangled regime.

It appears that on adsorption of the dispersive OVD, which is formulated from lower molecular weight HA, more of the entanglements are broken than when adsorption is from the longer chain cohesive OVD. In a surgical context, the structure of the adsorbed layer resulting in a higher dissipation could explain the medical observation that the dispersive OVD confers greater protection to the corneal endothelium.

Colloidal Probe Atomic Force Microscopy (AFM) was used to quantify the force associated with pulling off HA from a range of biomimetic surfaces exhibiting different surface charges (Chapter 5). The results are consistent with HA molecules from dispersive OVDs detaching by the simultaneous rupture of multiple anchoring points on the surface. On the other hand, it appears that HA molecules from cohesive OVDs sequentially break individual attachments, resulting in a higher work of adhesion. In a surgical context, it could be that this greater work of adhesion translates into more damage at the corneal endothelium when the OVD is aspirated.

The results we obtain with simple model substrates suggest that surface properties likely play a role, which merits future investigation.