Titanium Boston keratoprosthesis with corneal cell adhesive and bactericidal dual coating
Por:
Gómez SG, Guillem J, Martín-Gómez H, Mas C, Ginebra MP, Gil-Mur FX, Barraquer RI and Manero JM
Publicada:
1 nov 2023
Ahead of Print:
1 oct 2023
Resumen:
The Boston keratoprosthesis (BKPro) is a medical device used to restore vision in complicated cases of corneal blindness. This device is composed by a front plate of polymethylmethacrylate (PMMA) and a backplate usually made of titanium (Ti). Ti is an excellent biomaterial with numerous applications, although there are not many studies that address its interaction with ocular cells. In this regard, despite the good retention rates of the BKPro, two main complications compromise patients' vision and the viability of the prosthesis: imperfect adhesion of the corneal tissue to the upside of the backplate and infections. Thus, in this work, two topographies (smooth and rough) were generated on Ti samples and tested with or without functionalization with a dual peptide platform. This molecule consists of a branched structure that links two peptide moieties to address the main complications associated with BKPro: the well-known RGD peptide in its cyclic version (cRGD) as cell pro-adherent motif and the first 11 residues of lactoferrin (LF1-11) as antibacterial motif. Samples were physicochemically characterized, and their biological response was evaluated in vitro with human corneal keratocytes (HCKs) and against the gram-negative bacterial strain Pseudomonas aeruginosa. The physicochemical characterization allowed to verify the functionalization in a qualitative and quantitative manner. A higher amount of peptide was anchored to the rough surfaces. The studies performed using HCKs showed increased long-term proliferation on the functionalized samples. Gene expression was affected by topography and peptide functionalization. Roughness promoted alpha-smooth muscle actin (alpha-SMA) overexpression, and the coating notably increased the expression of extracellular matrix components (ECM). Such changes may favour the development of unwanted fibrosis, and thus, corneal haze. In contrast, the combination of the coating with a rough topography decreased the expression of alpha-SMA and ECM components, which would be desirable for the long-term success of the prosthesis. Regarding the antibacterial activity, the functionalized smooth and rough surfaces promoted the death of bacteria, as well as a perturbation in their wall definition and cellular morphology. Bacterial killing values were 58 % for smooth functionalised and 68 % for rough functionalised samples. In summary, this study suggests that the use of the dual peptide platform with cRGD and LF1-11 could be a good strategy to improve the in vitro and in vivo performance of the rough topography used in the commercial BKPro.
Filiaciones:
Gómez SG:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya, Barcelona Tech (UPC), Barcelona East School of Engineering (EEBE), 08019 Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, EEBE, 08019 Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034 Barcelona, Spain
Guillem J:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya, Barcelona Tech (UPC), Barcelona East School of Engineering (EEBE), 08019 Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, EEBE, 08019 Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034 Barcelona, Spain
Martín-Gómez H:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya, Barcelona Tech (UPC), Barcelona East School of Engineering (EEBE), 08019 Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, EEBE, 08019 Barcelona, Spain
Mas C:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya, Barcelona Tech (UPC), Barcelona East School of Engineering (EEBE), 08019 Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, EEBE, 08019 Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034 Barcelona, Spain
Ginebra MP:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya, Barcelona Tech (UPC), Barcelona East School of Engineering (EEBE), 08019 Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, EEBE, 08019 Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034 Barcelona, Spain
Institute for Bioengineering of Catalonia (IBEC), 08028 Barcelona, Spain
Gil-Mur FX:
Bioengineering Institute of Technology, Universitat Internacional de Catalunya, 08195 Barcelona, Spain
Barraquer RI:
Centro de Oftalmología Barraquer, Barcelona, Spain
Manero JM:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya, Barcelona Tech (UPC), Barcelona East School of Engineering (EEBE), 08019 Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, EEBE, 08019 Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034 Barcelona, Spain
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