title: Gelatin-Hyaluronic Acid Hydrogels with Tuned Stiffness to Counterbalance Cellular Forces and Promote Cell Differentiation.
abstract: Cells interact mechanically with their environment, exerting mechanical forces that probe the extracellular matrix (ECM). The mechanical properties of the ECM determine cell behavior and control cell differentiation both in 2D and 3D environments. Gelatin (Gel) is a soft hydrogel into which cells can be embedded. This study shows significant 3D Gel shrinking due to the high traction cellular forces exerted by the cells on the matrix, which prevents cell differentiation. To modulate this process, Gel with hyaluronic acid (HA) has been combined in an injectable crosslinked hydrogel with controlled Gel-HA ratio. HA increases matrix stiffness. The addition of small amounts of HA leads to a significant reduction in hydrogel shrinking after cell encapsulation (C2C12 myoblasts). We show that hydrogel stiffness counterbalanced traction forces of cells and this was decisive in promoting cell differentiation and myotube formation of C2C12 encapsulated in the hybrid hydrogels.
authors.affiliation: Center for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia, 46022, Spainggallego@ter.upv.es.
authors.forename: Sara
authors.initials: S
authors.lastname: Poveda-Reyes
authors.affiliation: Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8QQ, UK.
authors.forename: Vladimira
authors.initials: V
authors.lastname: Moulisova
authors.affiliation: Center for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia, 46022, Spainggallego@ter.upv.es.
authors.forename: Esther
authors.initials: E
authors.lastname: Sanmartín-Masiá
authors.affiliation: BIOFORGE Group, Centro de Investigación Científica y Desarrollo Tecnológico, Campus de Miguel Delibes, Universidad de Valladolid, Valladolid, 47011, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Quintanilla-Sierra
authors.affiliation: Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8QQ, UK. Manuel.Salmeron-Sanchez@glasgow.ac.uk.
authors.forename: Manuel
authors.initials: M
authors.lastname: Salmerón-Sánchez
authors.affiliation: Center for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia, 46022, Spainggallego@ter.upv.es. ggallego@ter.upv.es.|Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia 46022, Spain. ggallego@ter.upv.es.
authors.forename: Gloria Gallego
authors.initials: GG
authors.lastname: Ferrer
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D019245:Compressive Strength; D003432:Cross-Linking Reagents / Q000737:chemistry; D055119:Elastic Modulus; D005780:Gelatin / Q000494:pharmacology*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D024510:Muscle Development / Q000187:drug effects; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D013314:Stress, Mechanical; D034421:Sus scrofa; D014867:Water / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D006576:Heterocyclic Compounds, 4 or More Rings; D020100:Hydrogels; D011108:Polymers; D014867:Water; C472645:blebbistatin; D005780:Gelatin; D006820:Hyaluronic Acid
keywords: gelatin; hyaluronic acid; injectable hydrogels; matrix stiffness; myoblast differentiation