title: A model for the preliminary biological screening of potential keratoprosthetic biomaterials.
abstract: A series of in vitro screening assays for the preliminary selection of biomaterials for use in the fabrication of artificial corneas (keratoprostheses) (KPros) have been investigated. These screening assays assessed the initial binding of inflammatory and cell adhesive proteins, activation of inflammatory proteins, adhesion of keratocytes, epithelial cells and macrophages and the production of inflammatory cytokines by keratocytes contacting biomaterials. Central optic biomaterials were selected on the basis of low-inflammatory and cell adhesion potential. Peripheral skirt materials were selected on the basis of low-inflammatory potential but good cell adhesion to anchor the implant within the host cornea. Green fluorescent protein (GFP) gene transfer was used in a novel context to investigate cell invasion in the absence of external staining techniques. Confocal laser scanning microscopy and scanning electron microscopy were used to investigate GFP positive keratocyte invasion of porous materials. The results of in vitro assays were compared to a corneal organ culture system in which the biomaterials were assessed within a stromal environment. A range of polyurethane-based interpenetrating polymers with a range of water contents were screened. All materials showed low-inflammatory potential. A reduction in biomaterial water content induced an increase in complement C3 and fibronectin binding and in cell adhesion to materials, whilst differences in co-monomer formulation had little impact. The screening methods used in the current study provide a suitable preliminary assessment regime for the in vitro evaluation of potential KPro materials.
authors.affiliation: Biomedical Materials Research Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb Brighton BN2 4GJ, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Sandeman
authors.forename: A W
authors.initials: AW
authors.lastname: Lloyd
authors.forename: B J
authors.initials: BJ
authors.lastname: Tighe
authors.forename: V
authors.initials: V
authors.lastname: Franklin
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Lydon
authors.forename: C S C
authors.initials: CS
authors.lastname: Liu
authors.forename: D J
authors.initials: DJ
authors.lastname: Mann
authors.forename: S E
authors.initials: SE
authors.lastname: James
authors.forename: R
authors.initials: R
authors.lastname: Martin
mesh_terms: D001672:Biocompatible Materials; D002448:Cell Adhesion; D002478:Cells, Cultured; D003315:Cornea / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D003319:Corneal Stroma / Q000473:pathology / Q000503:physiopathology; D016039:Corneal Transplantation / Q000295:instrumentation* / Q000379:methods*; D019544:Equipment Failure Analysis / Q000379:methods*; D005240:Feasibility Studies; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008422:Materials Testing / Q000379:methods*; D010865:Pilot Projects; D019736:Prostheses and Implants
chemical_list: D001672:Biocompatible Materials; D015850:Interleukin-6