Spark plasma sintered titania-graphene oxide: A toothless keratoprosthesis for end-stage corneal blindness

The osteo-odonto keratoprosthesis (OOKP) remains a groundbreaking treatment for end-stage corneal blindness after 50 years, but is surgically complex and unsuitable for certain patients, particularly those without healthy teeth. We developed a novel keratoprosthesis (KPro) comprising spark plasma sintered titania-graphene oxide (TiGO) and a 5-mm PMMA optical cylinder, and evaluated its performance as an alternative to the tooth in the OOKP. The KPro's suitability for implantation was first demonstrated through the preservation of surface integrity, chemical structure, and mechanical strength following ethylene oxide sterilization. Mechanical pull-out tests showed that PMMA adhered more strongly to TiGO than to primate teeth after bonding with dental cement, suggesting that the same cement used in OOKP procedures can be used with TiGO skirts. In addition, in vitro studies confirmed TiGO's biocompatibility, supporting adhesion, proliferation, and viability of human corneal stromal fibroblasts. In a rabbit model of OOKP stage 1 surgery, the TiGO integrated successfully into dermal tissue, showing vascularized connective tissue with positive staining for collagen I and III and CD31. In stage 2 simulation, implantation of fibrovascularized KPro onto the ocular surface, under the nictitating membrane, was uneventful with no evidence of tissue melt, PMMA detachment, or adverse inflammatory response over six months. Immunohistological analysis showed that fibrovascular and immune cell markers in the implanted eyes were highest in the nictitating membrane proximal to the PMMA optical cylinder, decreased toward the distal regions, and were low throughout the host cornea. In conclusion, our TiGO-based KPro offers a promising alternative to OOKP, with advantages including a larger PMMA optical cylinder, less complex surgery, and broader surgical indications.