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The fibrous network of an extracellular matrix (ECM) possesses mechanical properties that convey critical biological functions in cell mechanotransduction. Engineered fibrous hydrogels show promise in emulating key aspects of ECM structure and functions. However, varying hydrogel mechanics without changing its architecture remains a challenge. A composite fibrous hydrogel is developed to vary gel stiffness without affecting its structure by controlling intrafibrillar crosslinking. The hydrogel is formed from aldehyde-modified cellulose nanocrystals and gelatin methacryloyl that provide the capability of intrafibrillar photocrosslinking. By varying the degree of gelatin functionalization with methacryloyl groups and/or photoirradiation time, the hydrogel's elastic modulus is changed by more than an order of magnitude, while preserving the same fiber diameter and pore size. The hydrogel is used to seed primary mouse lung fibroblasts and test the role of ECM stiffness on fibroblast contraction and activation. Increasing hydrogel stiffness by stronger intrafibrillar crosslinking results in enhanced fibroblast activation and increased fibroblast contraction force, yet at a reduced contraction speed. The developed approach enables the fabrication of biomimetic hydrogels with decoupled structural and mechanical properties, facilitating studies of ECM mechanics on tissue development and disease progression.
Chen et al. (Wed,) studied this question.