Spatially Controlled Dual-Functionalization of a Titanium Keratoprosthesis: A Proof-of-Concept In Vivo Study

Keratoprosthesis (KPro), an artificial corneal implant, is an established surgical option for restoring vision in severe corneal blindness; however, long-term outcomes remain limited by complications such as fibrosis and infection. Current biomaterial strategies generally lack the ability to address these distinct pathological processes at spatially defined implant-tissue interfaces. Here, we present a modified titanium KPro backplate with spatially controlled dual-functionalization, enabling spatially decoupled functionalization of opposing implant surfaces to address different biological challenges. The study was designed as an exploratory proof-of-concept and was not intended to determine the independent contribution or efficacy of either surface functionalization. The anterior surface was coated with antimicrobial silver nanoparticles, while the posterior surface was coated with a P17-derived peptide construct designed for surface immobilization and intended to target fibrosis-associated pathways. Side-specific surface modification was supported by scanning electron microscopy, fluorescence microscopy, and x-ray photoelectron spectroscopy. A proof-of-concept in vivo study was performed in a rabbit model over 1 month, comparing dual-functionalized and uncoated modified KPro devices. Corneal melting occurred in 3/6 control and 3/5 treated eyes; among eyes with melting, the mean number of affected corneal sectors was 3 and 1, respectively. Mean graft opacification was 60% in controls and 40% in treated eyes, and mean iris adhesion was 85% in control eyes and 70% in treated. Scanning electron microscopy qualitatively showed variable amounts of ECM-like fibrillar material and cellular-like structures at the implant interfaces, with no consistent qualitative difference between groups. Clinical findings compatible with infection were observed in 2/6 control eyes and 0/5 treated eyes. These findings support the technical feasibility of spatially controlled dual-functionalization and provide preliminary descriptive observations of short-term tissue-implant interactions during the first postoperative month, when complications are most frequent. This approach provides a basis for further evaluation of spatially programmed KPro surface engineering.