(33c) Reversible Control of Hydrogel Mechanics with Irreversible Photo-Mediated Reactions

Rosales, A. M., University of Texas at Austin
Vega, S., University of Pennsylvania
Del Rio, F., NIST
Burdick, J. A., University of Pennsylvania
Anseth, K. S., University of Colorado-Boulder
The extracellular matrix is a dynamic environment that undergoes cycles of stiffening and softening, especially during disease and development. A platform that recapitulates these dynamic changes will lead to better models that may shed light on the impact of matrix mechanics on disease mechanisms. Here, we present a strategy to reversibly control the modulus of hyaluronic-acid (HA) based hydrogels with light exposure through the use of photoresponsive crosslinkers. Hyaluronic acid polymers were functionalized with o-nitrobenzyl acrylates (14 mol%) and methacrylates (40 mol%), as well as short RGD peptides for cell adhesion (1 mol%). Hydrogels were formed with an initial elastic modulus of 14.8 kPa, as measured by AFM. These gels could be softened to 3 kPa upon exposure to 365 nm light, and subsequently re-stiffened with a photoinitator and visible light to 27.7 kPa. Because these moduli span a range of active mechanosensing for human mesenchymal stem cells (hMSCs), the cells were seeded onto the dynamic HA substrates and monitored for changes in cell morphology and YAP/TAZ nuclear localization at each stiffness condition. Reversible changes in cell spread area and YAP/TAZ nuclear localization were observed in response to the changes in substrate modulus. Due to their tunability and non-invasive stimulus, these innovative materials may be broadly useful for probing the effect of dynamic stiffness on many cell types.