title: Nanofiber-based hydrogels with extracellular matrix-based synthetic peptides for the prevention of capsular opacification.
abstract: Nanofiber-based hydrogels (nanogels) with different, covalently bound peptides were used as an extracellular environment for lens epithelial cells (LECs) in order to modulate the capsular opacification (CO) response after lens surgery in a porcine eye model. Lenses were divided into 15 groups (n = 4 per group), the lens content was removed and the empty capsules were refilled with nanogel without peptides and nanogels with 13 combinations of 5 different peptides: two laminin-derived, two fibronectin-derived, and one collagen IV-derived peptide representing cell adhesion motifs. A control group of 4 lenses was refilled with hyaluronan. After refilling, lenses were extracted from the porcine eye and cultured for three weeks. LECs were assessed for morphology and alpha smooth muscle actin (αSMA) expression using confocal laser scanning microscopy. Compared to hyaluronan controls, lenses filled with nanogel had less CO formation, indicated by a lower αSMA expression (P = 0.004). Microscopy showed differences in morphological cell response within the nanogel refilled groups. αSMA expression in these groups was highest in lenses refilled with nanogel without peptides (9.54 ± 11.29%). Overall, LEC transformation is reduced by the presence of nanogels and the response is improved even further by incorporation of extracellular matrix peptides representing adhesion motifs. Thus, nanomaterials targeting biological pathways, in our case interactions with integrin signaling, are a promising avenue toward reduction of CO. Further research is needed to optimize nanogel-peptide combinations that fully prevent CO.
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept. of Ophthalmology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Laboratory for Experimental Ophthalmology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, W.J. Kolff Institute, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. Electronic address: l.m.nibourg@umcg.nl.
authors.forename: Lisanne M
authors.initials: LM
authors.lastname: Nibourg
authors.affiliation: Nano Fiber Matrices B.V., Zernikepark 6-8, 9747 AN Groningen, The Netherlands.
authors.forename: Edith
authors.initials: E
authors.lastname: Gelens
authors.affiliation: Nano Fiber Matrices B.V., Zernikepark 6-8, 9747 AN Groningen, The Netherlands.
authors.forename: Menno R
authors.initials: MR
authors.lastname: de Jong
authors.affiliation: University of Groningen, University Medical Center Groningen, W.J. Kolff Institute, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Dept. of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Kuijer
authors.affiliation: University of Groningen, University Medical Center Groningen, W.J. Kolff Institute, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Dept. of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Theo G
authors.initials: TG
authors.lastname: van Kooten
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept. of Ophthalmology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, W.J. Kolff Institute, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Koopmans
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D058442:Capsule Opacification / Q000473:pathology / Q000517:prevention & control*; D024141:Collagen Type IV / Q000008:administration & dosage / Q000138:chemical synthesis; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000166:cytology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000008:administration & dosage* / Q000138:chemical synthesis; D005353:Fibronectins / Q000008:administration & dosage / Q000138:chemical synthesis; D019084:Fluorescent Antibody Technique, Indirect; D020100:Hydrogels; D007797:Laminin / Q000008:administration & dosage / Q000138:chemical synthesis; D007903:Lens Capsule, Crystalline / Q000166:cytology*; D007908:Lens, Crystalline / Q000166:cytology; D057139:Nanofibers; D009842:Oligopeptides / Q000008:administration & dosage* / Q000138:chemical synthesis; D009924:Organ Culture Techniques; D034421:Sus scrofa
chemical_list: D000199:Actins; D015415:Biomarkers; D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D020100:Hydrogels; D007797:Laminin; D009842:Oligopeptides
keywords: Capsule opacification; Cataract surgery; Epithelial–mesenchymal transition; Nanostructures; Prevention