Inflammation-Suppressing Cornea-in-a-Syringe with Anti-viral GF19 Peptide Promotes Regeneration in Rabbit Corneas with HSV-1 Keratitis

Uncontrolled inflammation, e.g., from HSV-1 viral infection, is a significant cause of corneal blindness due to tissue destruction resulting in ulceration or perforation. We developed an injectable Cornea-in-a-Syringe (CIS) sealant-filler containing linear carboxylated polymers of inflammation-suppressing 2-methacryloyloxyethyl phosphorylcholine polymer, regeneration-promoting collagen-like peptide and adhesive collagen-citrate glue. We also incorporated GF19, a modified anti-viral host defense peptide that blocked HSV-1 activity in vitro when released from silica nanoparticles (SiNP-G19). When tested in a surgically perforated and HSV-1 infected rabbit corneal model, the CIS alone suppressed inflammation, as shown by our clinical follow-up and cytokine expression changes, allowing corneal tissue regeneration. However, six months post-operation, only regenerated neocorneas previously treated with CIS+SiNP-GF19 showed vital structural and functional features that approached those of normal healthy corneas, and were HSV-1 virus-free. We have, therefore, demonstrated the feasibility of designing composite injectable biomaterials that suppress inflammation while inducing regeneration. Our injectable CIS can be further customized for specific patient needs, for example, conferring anti-viral activity to allow optimal regeneration in an infected tissue.