title: Sequential gelation of tyramine-substituted hyaluronic acid hydrogels enhances mechanical integrity and cell viability.
abstract: Tyramine-substituted hyaluronic acid (HA-Tyr) hydrogels formed by the oxidative coupling reaction of hydrogen peroxide (H2O2) and horseradish peroxidase (HRP) have been used for cellular encapsulation and protein delivery. Crosslinking density and gelation time can be tuned by altering the H2O2and HRP concentrations. Previous studies using HA-Tyr constructs report significant mechanical degradation after 21 days of culture. In this work, exogenous supplementation of HRP after initial gelation resulted in superior mechanical properties in acellular hydrogels and improved viability and proliferation in cell-laden constructs. Swelling of the acellular hydrogels was prevented in the samples receiving exogenous HRP. Monolayer studies showed no negative effect of relevant HRP concentrations on the viability of human adipose-derived stem cells (hASCs) and improved the viability of hASCs cultured with HRP and H2O2compared to H2O2alone. Taken together, this study demonstrates that HA-Tyr hydrogel properties could be modified by exogenous supplementation of HRP to tune scaffold degradation and improve cell viability by mitigating the negative effects of oxidative stress.
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Abu-Hakmeh
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Kung
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Mintz
authors.affiliation: School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kamal
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Cooper
authors.affiliation: Department of Mechanical Engineering, University of Delaware, Newark, DE, 19716, USA.
authors.forename: X Lucas
authors.initials: XL
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA. wanq@rpi.edu.
authors.forename: Leo Q
authors.initials: LQ
authors.lastname: Wan
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055119:Elastic Modulus; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D055595:Mechanical Phenomena / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology*
chemical_list: D020100:Hydrogels; D006820:Hyaluronic Acid; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D014439:Tyramine
keywords: Cell viability; Hyaluronic acid; Mechanical integrity; Oxidative stress