Abstract
Purpose :
Corneal infections constitute a silent epidemic with >800’000 new cases per year worldwide, often resulting in blindness, which is preventable with timely expert treatment. Surgical treatment options, such as corneal transplantation, are associated with high costs, and require specialist infrastructure and expertise, which are often unavailable in developing countries, leaving such cases untreated. Alternative standard of care procedures for the stabilization of corneal ulcers include cyanoacrylate-based or hydrogel (e.g. fibrin) based glues, which either exhibit a mismatched elastic modulus and exothermic gelation process, or are mechanically weak, rendering them unsuitable for certain types of defects.
To overcome these problems, we have developed an adhesive inspired by dopamine based mussel chemistry which is able to seal a corneal ulcer and serve as drug release system, as well as facilitate cell infiltration from the surrounding microenvironment.
Methods :
The adhesive is biodegradable and should support the regeneration of new transparent corneal tissue, and restoration of sight. For this, we mimic crosslinking aspects of catechol chemistry using a two-component glue based on chemically modified cold fish gelatin and hydrogen peroxide (H2O2) as an oxidizing agent to achieve a gelation temperature ≤ 25 °C. To achieve a fast (≤ 2 min) gelation time, as assessed via rheology and tube inversion techniques, that is compatible with the sensitive corneal ulcer environment, we evaluated different H2O2 concentrations.
Results :
Mussel inspired chemistry showed the thiourea and the catechol groups that crosslink to form a gel. Crosslinking with the surrounding tissue contributes to the adhesive. NMR data showed modification of cold-fish gelatin with the appearance of another peak at 6.7 ppm.
Tube inversion test showed complete gelation, 2 min after mixing.
In Vitro evaluation using NHDF cell showed that when cells were seeded on the gel surface after gelation, it mimicked a situation where healthy cells from the cornea proliferated and regenerated the injured cornea.
Ex Vivo evaluation in porcine non-infected defect (2 mm diameter) showed that the gelation happed after 3 min and pull out test for adhesion after 20 min showed that gel was firmly adherent to the defect.
Conclusions :
Our results show that the adhesive developed holds promise for corneal application and warrants further in vivo testing.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.