Cross-Linking Chemistry of Tyramine-Modified Hyaluronan Hydrogels Alters Mesenchymal Stem Cell Early Attachment and Behavior.
Given the significance of hydrogels as cell-instructive materials, it is important to understand how differences in their chemical and physical properties are able to direct cell fate. For example, it remains unclear how different hydrogel cross-linking chemistries and gelation mechanisms influence cell behavior. Here, we report on hyaluronan-tyramine (HA-Tyr) hydrogels prepared either with enzymatic cross-linking using horseradish peroxidase and H2O2or with visible light (500 nm) triggered gelation. We demonstrate that when hydrogels are polymerized to equivalent Young's moduli, the specific cross-linking chemistry of HA-Tyr hydrogels can have a substantial impact on mesenchymal stem cell (MSC) behavior. MSCs cultured on HA-Tyr hydrogels exhibit increased cell spread areas on enzymatically formed substrates relative to photo-cross-linked matrices. While enzymatically formed hydrogels led to MSCs exhibiting greater cell focal adhesion length, MSCs cultured on the photo-cross-linked matrices exhibited smaller cell spread area and shorter focal adhesion length but generated increased traction stress. These findings highlight the importance of understanding hydrogel cross-linking chemistries when the role of biophysical cues in regulating stem cell fate is investigated.
AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz 7270, Switzerland.|Cartilage Engineering + Regeneration, Department of Health, Science and Technology, ETH Zurich , Otto-Stern-Weg 7, Zürich 8093, Switzerland.
Claudia
0000-0002-3140-5663
C
Loebel
Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania 19104, United States.
Spencer E
0000-0002-7691-949X
SE
Szczesny
Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania 19104, United States.
Brian D
BD
Cosgrove
AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz 7270, Switzerland.
Mauro
M
Alini
Cartilage Engineering + Regeneration, Department of Health, Science and Technology, ETH Zurich , Otto-Stern-Weg 7, Zürich 8093, Switzerland.
Marcy
M
Zenobi-Wong
Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania 19104, United States.
Robert L
RL
Mauck
AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz 7270, Switzerland.
David
0000-0002-8500-6887
D
Eglin
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D055119:Elastic Modulus / Q000187:drug effects; D006735:Horseradish Peroxidase / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000378:metabolism; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D014439:Tyramine / Q000737:chemistry*
D001672:Biocompatible Materials; D020100:Hydrogels; D006820:Hyaluronic Acid; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D014439:Tyramine