| Synthetic corneal replacement or keratoprosthesis provides an alternative treatment to patients for whom donor cornea is incompatible or inaccessible. This study presented synthetic based corneal substitutes that facilitate cell ingrowth into a porous skirt while permitting vision through an optically transparent unit. The addition of cell adhesion components to PEGDA, PHEMAPEGDA, and PHEMA-PMMA structures was critical for assessing in vitro cell ingrowth and cell activity. Although cells colonized available polymer voids in vivo, the stable conjugation of cell adhesion components to the polymer skirt is imperative for host integration in the intended patient population. Keratoprosthesis recipients often have preexisting ocular diseases, ocular tissue injury, or a history of corneal graft failure. The diseased or damaged ocular tissue is more reluctant to integrate a synthetic structure compared to healthy eye tissue. Preclinical studies with rabbits have shown that an interconnected porous biomaterial, such as gas foamed polymer, can permit 3D tissue ingrowth and thereby stable host integration. However, results are less favorable in diseased ocular tissues. Compared to synthetic KPros, KPro models that combine synthetic and cell adhesion components (i.e. natural ECM components or peptides) show greater long term success in the target populations for KPro use.;KPro models presented in this study can be combined with cell adhesion components to encourage more stable host integration in the target user population. Specifically, the PHEMAPMMA based KPros are mechanically stable enough to be sutured, amenable to surface modification, and structurally appropriate for vision and tissue ingrowth. The goal is to use the Salt Porogen and Gas Foamed KPros, both PHEMA-PMMA based, as full thickness corneal replacement devices. Approximately 70% of the skirt of the Gas Foamed KPro provides an interconnected void space for tissue ingrowth. The skirt of the Salt Porogen KPro does not provide an interconnected void space for cell ingrowth, but the surface voids together with appropriate mass transport via the skirt could potentially facilitate host integration. A cell adhesive KPro skirt with a high density of cell permeable surface pores and physiologically relevant mass transport could potentially facilitate the stable integration of a KPro into ocular tissue. Biological, structural, and mechanical evaluations indicate that the presented PHEMAPMMA based KPros may be effective alternatives to currently available full thickness corneal replacement therapies. |
