Tunable, Photoreactive Hydrogel System to Probe Synergies between Mechanical and Biomolecular Cues on Adipose-Derived Mesenchymal Stem Cell Differentiation

The incorporation of the photoreactive molecule benzophenone into polyacrylamide hydrogels, allowing for orthogonal control over spatial incorporation of biomolecules and selective modulation of matrix stiffness, is described. Adipose-derived mesenchymal stem cells were cultured on matrices whose elastic moduli are tuned to ∼5, ∼14, and ∼37 kPa combined with an immobilized growth factor, bone morphogenic protein 2 (BMP-2), and their lineage differentiation was determined. BMP-2 was observed to have the most pronounced effect at the intermediate stiffness, while the lowest and highest stiffness hydrogels are directed by elasticity alone. Together, this approach describes a facile platform for fundamental studies of cell fate decisions in the context of both mechanical and biochemical cues and may lead to improved insight and effectiveness of stem cell therapies.