UC Santa Barbara

Hydrogel materials are commonly used to model the mechanical properties of the extracellular matrix (ECM). Viscoelastic properties of the ECM have recently emerged as a critical regulator of cellular behavior in 3D, and changes in ECM viscoelasticity are observed in fibrosis and many cancers. While hydrogel materials with tunable stiffness have been extensively used to study the effect of mechanics on cell behavior, most engineered hydrogel materials don’t well recapitulate the viscoelastic properties found in the ECM. Additionally, viscoelastic properties in diseased tissue often vary in both time and space. This thesis reports a simple approach for manipulating the viscoelasticity of norbornene-functionalized alginate hydrogels via photoaddition of PEG-thiol using thiol-norbornene photoclick chemistry. Hydrogel stiffness was controlled with calcium addition, and stress relaxation controlled by addition of PEG, independently of stiffness. Addition of PEG produced gels exhibiting faster stress relaxation and increased creep. When evaluated in cells, faster relaxation led to increased cell volume and decreased sphericity in MSCs, and greater proliferation in breast cancer cells. Photopatterning of the gel embedded with MSCs led to morphologies in PEG-patterned regions consistent with fast-relaxing behavior and morphologies in non-patterned regions consistent with slow-relaxing behavior.