Abstract
Purpose :
Elastic soft hydrogels are widely utilized by living organisms to protect delicate tissues. This type of material is characterized by being truly elastic in nature, but the value of the storage modulus is exceptionally small. Inspired by the unique properties of natural soft hydrogels, a synthetic hyaluronic acid based soft hydrogel was developed and evaluated for its potential for the treatment of dry eye disease.
Methods :
Hyaluronic acid was modified with vinylsulfone groups (HA-VS) and thiol groups (HA-SH) separated. The hydrogel was formed by mixing HA-VS and HA-SH at physiological condition. The mechanical properties were tested using an Anton Paar rheometer. For precorneal retention of hydrogel, HA-VS was labeled with fluorescent before forming hydrogel with HA-SH. Rabbits were anesthetized and the precorneal clearance of hydrogel were quantified using a fluorescent imager. For the veterinary clinical study, dog patients with dry eye syndrome and previously treated with BID cyclosporine in combination with 4-6 times a day artificial tear for at least 12 months were enrolled in the study. All patients were switched to a BID application of cyclosporine and soft hydrogel for 1 months. Seven clinical signs, including Schirmer’s tests, conjunctival hyperemia and corneal staining, were evaluated before and after the soft hydrogel treatment.
Results :
We developed a theoretical model and successfully synthesized soft hydrogel using modified hyaluronic acid as hydrogel backbone. The soft hydrogel has several unique properties that are distinguished from conventional hydrogels. The soft hydrogel elastically deformed instead of viscously flowed when a low stress was applied. The storage modulus of the hydrogel is below 1 Pa but larger than loss modulus at low frequency oscillation. The soft gel viscously flowed at large deformation, but the elasticity of the hydrogel could be retained after a large deformation. The precorneal retention of fluorescent labeled soft hydrogel was found to be hours compares to minutes for non-crosslinked polymers. The soft hydrogel also demonstrated significant anti-inflammatory effect. In the veterinary study, more than 50% of cyclosporine non-responding dog patients had at least 4 clinical signs improvement after the 1 month treatment.
Conclusions :
Low-density chemically crosslinked hyaluronic acid soft hydrogel could be a potential treatment modality for dry eye disease.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.