title: Surface Modification of PMMA to Improve Adhesion to Corneal Substitutes in a Synthetic Core-Skirt Keratoprosthesis.
abstract: Patients with advanced corneal disease do poorly with conventional corneal transplantation and require a keratoprosthesis (KPro) for visual rehabilitation. The most widely used KPro is constructed using poly(methyl methacrylate) (PMMA) in the central optical core and a donor cornea as skirt material. In many cases, poor adherence between the PMMA and the soft corneal tissue is responsible for device "extrusion" and bacterial infiltration. The interfacial adhesion between the tissue and the PMMA was therefore critical to successful implantation and device longevity. In our approach, we modified the PMMA surface using oxygen plasma (plasma group); plasma followed by calcium phosphate (CaP) coating (p-CaP); dopamine followed by CaP coating (d-CaP); or plasma followed by coating with (3-aminopropyl)triethoxysilane (3-APTES). To create a synthetic KPro model, we constructed and attached 500 μm thick collagen type I hydrogel on the modified PMMA surfaces. Surface modifications produced significantly improved interfacial adhesion strength compared to untreated PMMA (p < 0.001). The p-CaP group yielded the best interfacial adhesion with the hydrogel (177 ± 27 mN/cm(2)) followed by d-CaP (168 ± 31 mN/cm(2)), 3-APTES (145 ± 12 mN/cm(2)), and plasma (119 ± 10 mN/cm(2)). Longer-term stability of the adhesion was achieved by d-CaP, which, after 14 and 28 days of incubation in phosphate buffered saline, yielded 164 ± 25 mN/cm(2) (p = 0.906 compared to adhesion at day 1) and 131 ± 20 mN/cm(2) (p = 0.053), respectively. In contrast, significant reduction of adhesion strength was observed in p-CaP group over time (p < 0.001). All surface coatings were biocompatible to human corneal stromal fibroblasts, except for the 3-APTES group, which showed no live cells at 72 h of culture. In contrast, cells on d-CaP surface showed good anchorage, evidenced by the expression of focal adhesion complex (paxillin and vinculin), and prominent filopodia protrusions. In conclusion, d-CaP can not only enhance and provide stability to the adhesion of collagen hydrogel on the PMMA surface but also promote biointegration.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University , Singapore 639798, Singapore.|Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute , Singapore 169856, Singapore.
authors.forename: Andri K
authors.initials: AK
authors.lastname: Riau
authors.affiliation: Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute , Singapore 169856, Singapore.
authors.forename: Debasish
authors.initials: D
authors.lastname: Mondal
authors.affiliation: Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute , Singapore 169856, Singapore.
authors.forename: Gary H F
authors.initials: GH
authors.lastname: Yam
authors.affiliation: Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute , Singapore 169856, Singapore.
authors.forename: Melina
authors.initials: M
authors.lastname: Setiawan
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University , Singapore 639798, Singapore.|Center for Biomimetic Sensor Science, Nanyang Technological University , Singapore 637553, Singapore.
authors.forename: Bo
authors.initials: B
authors.lastname: Liedberg
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University , Singapore 639798, Singapore.
authors.forename: Subbu S
authors.initials: SS
authors.lastname: Venkatraman
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University , Singapore 639798, Singapore.|Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute , Singapore 169856, Singapore.|Singapore National Eye Center , Singapore 168751, Singapore.|Department of Clinical Sciences, Duke-NUS Graduate Medical School , Singapore 169857, Singapore.
authors.forename: Jodhbir S
authors.initials: JS
authors.lastname: Mehta
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry* / Q000633:toxicity; D002448:Cell Adhesion / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D003315:Cornea / Q000166:cytology*; D006801:Humans; D020100:Hydrogels; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D019736:Prostheses and Implants; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D003094:Collagen; D019904:Polymethyl Methacrylate
keywords: adhesion; biointegration; collagen hydrogel; dopamine; hydrophobic; keratoprosthesis; plasma treatment; polymer