Hydrogels with Dual Gradients of Mechanical and Biochemical Cues for Deciphering Cell-Niche Interactions.

Cell niche is a multifactorial environment containing complex interactions between biochemical and physical cues. Although extensive studies have examined the effects of biochemical or physical cues alone on cell fate, how biochemical and mechanical signals interact to influence cell fates remains largely unknown. To address this challenge, here we report a polyethylene glycol-based gradient hydrogel platform as biomimetic cell niche containing independently tunable matrix stiffness and biochemical ligand density. The versatility of this platform is demonstrated by fabricating and characterizing single gradient or orthogonally aligned dual gradient hydrogels. These gradients result in differential elongation and spreading of human fibroblasts. Both hydrogel stiffness and biochemical ligand density are independently tunable by sequential photopolymerization. By controlling light exposure, a broad range of hydrogel stiffness and different types/doses of biochemical ligands can be incorporated. Such tunability facilitates customization of this platform for investigating complex cell-niche interactions associated with various cell types, such as stem cells and cancer cells. The outcomes of such studies may help identify optimal niche cues to promote desiralbe stem fates and tissue regeneration or inhibit diseases progression.