title: Hyaluronic Acid Hydrogels Formed in Situ by Transglutaminase-Catalyzed Reaction.
abstract: Enzymatically cross-linked hydrogels can be formed in situ and permit highly versatile and selective tethering of bioactive molecules, thereby allowing for a wealth of applications in cell biology and tissue engineering. While a number of studies have reported the bioconjugation of extracellular matrix (ECM) proteins and peptides into such matrices, the site-specific incorporation of biologically highly relevant polysaccharides such as hyaluronic acid (HA) has thus far not been reported, limiting our ability to reconstruct this key feature of the in vivo ECM. Here we demonstrate a novel strategy for transglutaminase-mediated covalent linking of HA moieties to a synthetic poly(ethylene glycol) (PEG) macromer resulting in the formation of hybrid HA-PEG hydrogels. We characterize the ensuing matrix properties and demonstrate how these cytocompatible gels can serve to modulate the cellular phenotype of human mammary cancer epithelial cells as well as mouse myoblasts. The use of HA as a novel building block in the increasingly varied library of synthetic PEG-based artificial ECMs should have applications as a structural as well as a signaling component and offers significant potential as an injectable matrix for regenerative medicine.
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL) , Lausanne CH 1015, Switzerland.|Biomechanics Section, Mechanical Engineering Department, KU Leuven , Celestijnenlaan 300, Leuven 3001, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Ranga
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL) , Lausanne CH 1015, Switzerland.|Institute of Chemical Sciences and Engineering, School of Basic Sciences, EFFL , Lausanne, CH 1015, Switzerland.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Lutolf
authors.affiliation: Science for Life Laboratory, Division of Polymer Chemistry, Department of Chemistry-Ångström, Uppsala University , Uppsala SE 751 21, Sweden.
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
authors.affiliation: Science for Life Laboratory, Division of Polymer Chemistry, Department of Chemistry-Ångström, Uppsala University , Uppsala SE 751 21, Sweden.
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Ossipov
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D006820:Hyaluronic Acid; D011503:Transglutaminases