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Abstract Recently, it has been recognized that natural extracellular matrix (ECM) and tissues are viscoelastic, while only elastic properties have been investigated in the past. How the viscoelastic matrix regulates stem cell patterning is critical for cell‐ECM mechano‐transduction. Here, this study fabricated different methacrylated hyaluronic acid (HA) hydrogels using covalent cross–linking, consisting of two gels with similar elasticity (stiffness) but different viscoelasticity, and two gels with similar viscoelasticity but different elasticity (stiffness). Meanwhile, a second set of dual network hydrogels are fabricated containing both covalent and coordinated cross–links. Human spinal cord organoid (hSCO) patterning in HA hydrogels and co‐culture with isogenic human blood vessel organoids (hBVOs) are investigated. The viscoelastic hydrogels promote regional hSCO patterning compared to the elastic hydrogels. More viscoelastic hydrogels can promote dorsal marker expression, while softer hydrogels result in higher interneuron marker expression. The effects of viscoelastic properties of the hydrogels become more dominant than the stiffness effects in the co‐culture of hSCOs and hBVOs. In addition, more viscoelastic hydrogels can lead to more Yes‐associated protein nuclear translocation, revealing the mechanism of cell‐ECM mechano‐transduction. This research provides insights into viscoelastic behaviors of the hydrogels during human organoid patterning with ECM‐mimicking in vitro microenvironments for applications in regenerative medicine.
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Hyaluronic acid-based hydrogels to study cancer cell behaviors
Hyaluronic acid (HA) is a natural polysaccharide and a key component of the extracellular matrix (ECM) in many tissues. Therefore, HA-based biomaterials are extensively utilized to create three dimensional ECM mimics to study cell behaviors in vitro . Specifically, derivatives of HA have been commonly used to fabricate hydrogels with controllable properties. In this review, we discuss the various chemistries employed to fabricate HA-based hydrogels as a tunable matrix to mimic the cancer microenvironment and subsequently study cancer cell behaviors in vitro . These include Michael-addition reactions, photo-crosslinking, carbodiimide chemistry, and Diels–Alder chemistry. The utility of these HA-based hydrogels to examine cancer cell behaviors such as proliferation, migration, and invasion in vitro in various types of cancer are highlighted. Overall, such hydrogels provide a biomimetic material-based platform to probe cell-matrix interactions in cancer cells in vitro and study the mechanisms associated with cancer progression.
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- Award ID(s):
- 1749837
- PAR ID:
- 10275629
- Date Published:
- Journal Name:
- Journal of Materials Chemistry B
- ISSN:
- 2050-750X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D1TB00963J
