Severe HSV-1 infection can cause blindness due to tissue damage from severe inflammation. Due to the high risk of graft failure in HSV-1-infected individuals, cornea transplantation to restore vision is often contraindicated. We tested the capacity for cell-free biosynthetic implants made from recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) to suppress inflammation and promote tissue regeneration in the damaged corneas. To block viral reactivation, we incorporated silica dioxide nanoparticles releasing KR12, the small bioactive core fragment of LL37, an innate cationic host defense peptide produced by corneal cells. KR12 is more reactive and smaller than LL37, so more KR12 molecules can be incorporated into nanoparticles for delivery. Unlike LL37, which was cytotoxic, KR12 was cell-friendly and showed little cytotoxicity at doses that blocked HSV-1 activity in vitro, instead enabling rapid wound closure in cultures of human epithelial cells. Composite implants released KR12 for up to 3 weeks in vitro. The implant was also tested in vivo on HSV-1-infected rabbit corneas where it was grafted by anterior lamellar keratoplasty. Adding KR12 to RHCIII-MPC did not reduce HSV-1 viral loads or the inflammation resulting in neovascularization. Nevertheless, the composite implants reduced viral spread sufficiently to allow stable corneal epithelium, stroma, and nerve regeneration over a 6-month observation period.

The human cornea acts as a protective covering for the eye and plays an important role in light transmission into the eye for vision. Corneal defects due to trauma, infection, or disease can have detrimental effects on the vision, and severe cases lead to vision loss. Twenty-three million people are estimated to be affected by corneal blindness worldwide. Treatment involves corneal transplantation surgery, but there is a severe shortage of donor corneas worldwide. Furthermore, patients with severe pathologies risk rejecting conventional corneal transplantation, thus leaving them untreated. Therefore, there is an urgent need to develop new therapies to replace traditional corneal transplant surgery. This review focuses on recent potential biomaterials development for corneal regeneration and repair. It includes cell-based therapies, cell-free regeneration-inducing biomaterials, and injectable or in-situ gelation-based biomaterials for patients with a high risk of graft failure. It also consists of the emerging role of exosomes and extracellular vesicles in corneal infections and regeneration.