Magnetically-Driven Hydrogel Surfaces For Dynamic Stiffness Modulation For Modulating Macrophage Behavior

During the host response towards implanted biomaterials, macrophages can shift phenotype rapidly upon changes in their microenvironment within the host tissue. Exploration of this phenomenon can gain significantly from the development of adequate tools. Creating dynamic surface alterations on classical hydrogel substrates presents challenges, particularly when integrating them with cell cultivation and monitoring processes. However, having the capability to dynamically manipulate the stiffness of biomaterial surfaces holds significant potential. We introduce magnetically actuated dynamic surfaces (MadSurface) tailored to induce reversible stiffness changes on polyacrylamide hydrogel substrates with embedded magnetic microparticles in a time-controllable manner. Our investigation focused on exploring the potential of MadSurface in dynamically modulating macrophage behavior in a programmable manner. We achieved a consistent modulation by subjecting the MadSurface to a pulsed magnetic field with a frequency of 0.1 Hz and a magnetic field flux density of 50 mT and analyzed exposed cells using flow cytometry and ELISA. At the single cell level, we identified a sub-population for which the dynamic stiffness conditions in conjunction with the pulsed magnetic field increased the expression of CD206 in M1-activated THP-1 cells, indicating a consistent shift toward M2 anti-inflammatory phenotype on MadSurface. At the population level, this effect was mostly hindered in the first 24 hours. MadSurface approach can create controlled environments to advance our understanding of the interplay between dynamic surface mechanics and macrophage behavior.