RT Journal Article
SR Electronic
T1 Spatial control of viscoelasticity in phototunable hyaluronic acid hydrogels
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 646778
DO 10.1101/646778
A1 Erica Hui
A1 Kathryn I. Gimeno
A1 Grant Guan
A1 Steven R. Caliari
YR 2019
UL http://biorxiv.org/content/early/2019/05/27/646778.abstract
AB Viscoelasticity has emerged as a critical regulator of cell behavior. However, there is an unmet need to develop biomaterials where viscoelasticity can be spatiotemporally tuned to mimic the dynamic and heterogeneous nature of tissue microenvironments. Toward this objective, we developed a modular hyaluronic acid hydrogel system combining light-mediated covalent and supramolecular crosslinking to afford spatiotemporal control of network viscoelastic properties. Covalently crosslinked elastic hydrogels or viscoelastic hydrogels combining covalent and supramolecular interactions were fabricated to match healthy and fibrotic liver stiffness. LX-2 human hepatic stellate cells cultured on viscoelastic substrates displayed reduced spreading, less actin stress fiber organization, and lower myocardin-related transcription factor A (MRTF-A) nuclear localization compared to cells on elastic hydrogels. We further demonstrated the dynamic capabilities of our hydrogel system through photomediated secondary incorporation of either covalent or supramolecular crosslinks to modulate viscoelastic properties. We used photopatterning to create hydrogel models with well-controlled patterned regions of stiff elastic mechanics representing fibrotic tissue nodules surrounded by regions of soft viscoelastic hydrogel mimicking healthy tissue. Cells responded to the local mechanics of the patterned substrate with increased spreading in fibrosis-mimicking regions. Together, this work represents an important step forward toward the creation of hydrogel models with spatiotemporal control of both stiffness and viscoelastic cell-instructive cues.