Multifunctional Bandage Lens and Bioadhesive for the Treatment of Corneal Wounds
Abstract
Rationale: Damage to the eye occurs in a large number of military-related injuries, with >275,000 eye injuries in the U.S. armed services from 2000 to 2017, which are often associated with loss or diminished sight. How quickly these injuries are repaired are important factors that affect long-term eyesight. We propose below a specialized adhesive bandage lens that can reconstruct the eye contour after an injury and minimize inflammation, adhesions, and infection. Therefore, this research directly addresses the FY22 Vision Research Program Focus Areas Eye injury …as related to military exposure, including blast, … thermal, or chemical trauma as well as treatment of eye injuries in prolonged field care settings. Our proposed research is advancing more mature research, based on our experience and expertise with proteoglycan 4 (PRG4), gelatin methacryloyl (GelMA), and ophthalmic biomaterials. We co-discovered PRG4 on the ocular surface and demonstrated it has lubricating function there and on ophthalmic biomaterials. PRG4 has anti-inflammatory and anti-fibrotic properties; we showed recombinant human PRG4 (rhPRG4) dampens inflammation-induced cytokine expression in corneal epithelial cells. Finally, we showed rhPRG4 contributes to tissue regeneration and wound healing. We now have strong preliminary data showing GelMA, which has previously been studied for the treatment of corneal injuries, effectively delivers rhPRG4 and antibiotics. However, GelMA use for corneal wounds in emergent settings has been limited by imprecise eye contour recreation. We propose to overcome this by in situ crosslinking of GelMA under a bandage lens, leveraging the multifunctional PRG4 gradually released under the bandage lens to promote healing, and by slowly releasing antibiotics to prevent infection. Our novel lens can be used by first responders in prolonged field care settings. Objective: The objective of this work is to develop a bandage lens lubricated by rhPRG4 together with rhPRG4- and antibiotic-loaded GelMA that helps the proper filling of corneal defects followed by GelMA in place crosslinking with light. We believe that the rhPRG4-lubricated lens together with rhPRG4- and antibiotic-loaded GelMA, that is crosslinked directly on the eye, will lead to rapid closure and prevent adhesions, infection, and scarring, enhancing corneal wound healing. This will be tested by the following Aims: Aim 1: Assess and optimize the lubricating properties of rhPRG4 on bandage lenses, the physical/adhesive properties of GelMA, and rhPRG4 and antibiotic release kinetics from GelMA. Aim 2: Confirm the activity of rhPRG4 and antibiotic eluted from bandage lens and GelMA, respectively, as assessed by modulating inflammation and scarring, as well as preventing infection in cells. Aim 3: Evaluate the ability of the rhPRG4-lubricated bandage lens together with rhPRG4- and gentamicin-loaded GelMA adhesive, crosslinked in place, in rabbits to modulate inflammation, prevent scaring and infection, and improve corneal wound healing. Impact: The expected short-term impact of this work on the field of eye trauma care is data supporting a new rhPRG4-lubricated bandage lens combined with properly contoured rhPRG4- and antibody-loaded adhesive GelMA to treat corneal wounds. This has the potential to open up and help create new avenues of research in the context of PRG4 being used together with GelMA to treat other types of wounds. The potential long-term impact of this work lies in paving the way toward testing this specialized lens in people, thus translating a new, rapidly deployable treatment tool for cornea wounds in field settings. Given that our rhPRG4 has been successfully tested clinically for treating dry eyes in people, and has been shown to be both safe and effective, the potential for faster clinical translation, i.e., getting our new lens into the clinic to help people, is significant.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310566
Entities
People
- Tannin Schmidt
Organizations
- United States Army
- University of Connecticut Health Center