title: Accelerated Development of Supramolecular Corneal Stromal-Like Assemblies from Corneal Fibroblasts in the Presence of Macromolecular Crowders.
abstract: Tissue engineering by self-assembly uses the cells' secretome as a regeneration template and biological factory of trophic factors. Despite the several advantages that have been witnessed in preclinical and clinical settings, the major obstacle for wide acceptance of this technology remains the tardy extracellular matrix formation. In this study, we assessed the influence of macromolecular crowding (MMC)/excluding volume effect, a biophysical phenomenon that accelerates thermodynamic activities and biological processes by several orders of magnitude, in human corneal fibroblast (HCF) culture. Our data indicate that the addition of negatively charged galactose derivative (carrageenan) in HCF culture, even at 0.5% serum, increases by 12-fold tissue-specific matrix deposition, while maintaining physiological cell morphology and protein/gene expression. Gene analysis indicates that a glucose derivative (dextran sulfate) may drive corneal fibroblasts toward a myofibroblast lineage. Collectively, these results indicate that MMC may be suitable not only for clinical translation and commercialization of tissue engineering by self-assembly therapies, but also for the development of in vitro pathophysiology models.
authors.affiliation: 1 Network of Excellence for Functional Biomaterials (NFB), Bioscience Research Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .
authors.forename: Pramod
authors.initials: P
authors.lastname: Kumar
authors.affiliation: 1 Network of Excellence for Functional Biomaterials (NFB), Bioscience Research Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .
authors.forename: Abhigyan
authors.initials: A
authors.lastname: Satyam
authors.affiliation: 1 Network of Excellence for Functional Biomaterials (NFB), Bioscience Research Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .
authors.forename: Xingliang
authors.initials: X
authors.lastname: Fan
authors.affiliation: 1 Network of Excellence for Functional Biomaterials (NFB), Bioscience Research Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .
authors.forename: Yury
authors.initials: Y
authors.lastname: Rochev
authors.affiliation: 2 Conway Institute of Biomolecular & Biomedical Research, University College Dublin , Dublin, Ireland .
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Rodriguez
authors.affiliation: 3 School of Chemistry & Chemical Biology, University College Dublin , Dublin, Ireland .
authors.forename: Alexander
authors.initials: A
authors.lastname: Gorelov
authors.affiliation: 4 Alimentary Glycoscience Research Cluster, NUI Galway , Galway, Ireland .
authors.forename: Lokesh
authors.initials: L
authors.lastname: Joshi
authors.affiliation: 5 Department of Bioengineering, Faculty of Engineering, National University of Singapore , Singapore, Singapore .|6 Tissue Engineering Programme, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, Singapore .
authors.forename: Michael
authors.initials: M
authors.lastname: Raghunath
authors.affiliation: 1 Network of Excellence for Functional Biomaterials (NFB), Bioscience Research Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .
authors.forename: Abhay
authors.initials: A
authors.lastname: Pandit
authors.affiliation: 1 Network of Excellence for Functional Biomaterials (NFB), Bioscience Research Building, National University of Ireland Galway (NUI Galway) , Galway, Ireland .
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Zeugolis
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D003319:Corneal Stroma / Q000166:cytology* / Q000378:metabolism; D003470:Culture Media; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans
chemical_list: D003470:Culture Media