title: Application of Graphene as Candidate Biomaterial for Synthetic Keratoprosthesis Skirt.
abstract: OBJECTIVE
  Synthetic keratoprostheses are required for visual rehabilitation in patients with end-stage corneal blindness. This study aimed to assess the biocompatibility of graphene material and its potential as a novel synthetic keratoprosthesis skirt material for corneal tissue engineering.
  
  
  METHODS
  Human corneal stromal fibroblasts were cultured on material surfaces including pristine graphene film, graphene foam, pristine titanium (Ti) discs, and tissue culture plastic surface (TCPS). Cell attachment was assayed by immunostaining of paxillin and vinculin. Cell viability and proliferation were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Click iT 5-ethynyl-2'-deoxyuridine (EdU) assays. The growth of fibroblasts on three-dimensional graphene foam was examined by scanning electron microscopy, and cytokine release was analyzed by enzyme-linked immunosorbent assay. Graphene films were implanted into rabbit corneal stromal pockets and examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography, in vivo confocal microscopy, and histology.
  
  
  RESULTS
  Pristine graphene demonstrated good biocompatibility with human stromal fibroblasts in terms of cell adhesion, viability, and proliferation. Cells on graphene films showed higher number than on TCPS control. Cells grown on graphene had 10% more proliferation than on Ti. The expression levels of IL-6 and IL-8 were reduced when cells were seeded on graphene foam as compared to Ti and graphene film. Implantation of graphene film into rabbit stroma (n = 6) did not show any signs of infection, neovascularization, or inflammation.
  
  
  CONCLUSIONS
  Graphene displayed excellent short-term biocompatibility with corneal cells and tissue. This demonstrates that graphene can be developed as a tissue engineering material for use in cornea.
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Xiao Wei
authors.initials: XW
authors.lastname: Tan
authors.affiliation: School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore.
authors.forename: Brianna
authors.initials: B
authors.lastname: Thompson
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Aris
authors.initials: A
authors.lastname: Konstantopoulos
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Tze Wei
authors.initials: TW
authors.lastname: Goh
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Melina
authors.initials: M
authors.lastname: Setiawan
authors.affiliation: Singapore Eye Research Institute, Singapore 3Duke-NUS Graduate Medical School, Singapore.
authors.forename: Gary Hin-Fai
authors.initials: GH
authors.lastname: Yam
authors.affiliation: Singapore Eye Research Institute, Singapore 3Duke-NUS Graduate Medical School, Singapore 4Singapore National Eye Centre, Singapore.
authors.forename: Donald
authors.initials: D
authors.lastname: Tan
authors.affiliation: School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore.
authors.forename: Khiam Aik
authors.initials: KA
authors.lastname: Khor
authors.affiliation: Singapore Eye Research Institute, Singapore 2School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 3Duke-NUS Graduate Medical School, Singapore 4Singapore National Eye Centre, Singapore.
authors.forename: Jodhbir S
authors.initials: JS
authors.lastname: Mehta
mesh_terms: D000818:Animals; D001766:Blindness / Q000534:rehabilitation*; D020099:Coated Materials, Biocompatible; D003319:Corneal Stroma / Q000648:ultrastructure*; D006108:Graphite; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D019736:Prostheses and Implants; D011474:Prosthesis Design; D011817:Rabbits; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020099:Coated Materials, Biocompatible; D006108:Graphite