Abstract
During the host response toward implanted biomaterials, macrophages can shift phenotypes rapidly upon changes in their microenvironment within the host tissue. Exploration of this phenomenon can benefit significantly from the development of adequate tools. Creating cell microenvironment 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 cell microenvironment on biomaterial surfaces holds significant potential. We introduce magnetically actuated hydrogels ((Mad)Surface) 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 magnetic fields and (Mad)Surfaces in dynamically modulating macrophage behavior in a programmable manner. We achieved a consistent modulation by subjecting the (Mad)Surface 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 subpopulation 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 the M2 anti-inflammatory phenotype on (Mad)Surface. At the population level, this effect was mostly hindered in the culture period utilized in this work. The (Mad)Surface approach advances our understanding of the interplay between magnetic field, cell microenvironment alterations, and macrophage behavior.