Magnetically\nDriven Hydrogel Surfaces for Modulating\nMacrophage Behavior

During the host response toward implanted biomaterials,\nmacrophages\ncan shift phenotypes rapidly upon changes in their microenvironment\nwithin the host tissue. Exploration of this phenomenon can benefit\nsignificantly from the development of adequate tools. Creating cell\nmicroenvironment alterations on classical hydrogel substrates presents\nchallenges, particularly when integrating them with cell cultivation\nand monitoring processes. However, having the capability to dynamically\nmanipulate the cell microenvironment on biomaterial surfaces holds\nsignificant potential. We introduce magnetically actuated hydrogels\n(<sub>Mad</sub>Surface) tailored to induce reversible stiffness changes\non polyacrylamide hydrogel substrates with embedded magnetic microparticles\nin a time-controllable manner. Our investigation focused on exploring\nthe potential of magnetic fields and <sub>Mad</sub>Surfaces in dynamically\nmodulating macrophage behavior in a programmable manner. We achieved\na consistent modulation by subjecting the <sub>Mad</sub>Surface to\na pulsed magnetic field with a frequency of 0.1 Hz and a magnetic\nfield flux density of 50 mT and analyzed exposed cells using flow\ncytometry and ELISA. At the single-cell level, we identified a subpopulation\nfor which the dynamic stiffness conditions in conjunction with the\npulsed magnetic field increased the expression of CD206 in M1-activated\nTHP-1 cells, indicating a consistent shift toward the M2 anti-inflammatory\nphenotype on <sub>Mad</sub>Surface. At the population level, this\neffect was mostly hindered in the culture period utilized in this\nwork. The <sub>Mad</sub>Surface approach advances our understanding\nof the interplay between magnetic field, cell microenvironment alterations,\nand macrophage behavior.