Hydrogels with Dynamically Controllable Mechanics and Biochemistry for 3D Cell Culture Platforms

Many cell-matrix interaction studies have proved that dynamic changes in the extracellular matrix (ECM) are crucial to maintain cellular properties and behaviors. Thus, developing materials that can recapitulate the dynamic attributes of the ECM is highly desired for three-dimensional (3D) cell culture platforms. To this end, we sought to develop a hydrogel system that would enable dynamic and reversible turning of its mechanical and biochemical properties, thus facilitating the control of cell culture to imitate the natural ECM. Herein, a hydrogel with dynamic mechanics and a biochemistry based on an addition-fragmentation chain transfer (AFCT) reaction was constructed. Thiol-modified hyaluronic acid (HA) and allyl sulfide-modified ε-poly-L-lysine (EPL) were synthesized to form hydrogels, which were non-swellable and biocompatible. The reversible modulus of the hydrogel was first achieved through the AFCT reaction; the modulus can also be regulated stepwise by changing the dose of UVA irradiation. Dynamic patterning of fluorescent markers in the hydrogel was also realized. Therefore, this dynamically controllable hydrogel has great potential as a 3D cell culture platform for tissue engineering applications.