Temporal Control over Macrophage Phenotype and the Host Response via Magnetically Actuated Scaffolds

Cyclic strain generated at the cell-material interface is critical for the engraftment of biomaterials. Mechanosensitive immune cells, macrophages regulate the host-material interaction immediately after implantation by priming the environment and remodeling ongoing regenerative processes. This study investigated the ability of mechanically active scaffolds to modulate macrophage function in vitro and in vivo. Remotely actuated magnetic scaffolds enhance the phenotype of murine classically activated (M1) macrophages, as shown by the increased expression of the M1 cell-surface marker CD86 and increased secretion of multiple M1 cytokines. When scaffolds were implanted subcutaneously into mice and treated with magnetic stimulation for 3 days beginning at either day 0 or day 5 post-implantation, the cellular infiltrate was enriched for host macrophages. Macrophage expression of the M1 marker CD86 was increased, with downstream effects on vascularization and the foreign body response. Such effects were not observed when the magnetic treatment was applied at later time points after implantation (days 12-15). These results advance our understanding of how remotely controlled mechanical cues, namely, cyclic strain, impact macrophage function and demonstrate the feasibility of using mechanically active nanomaterials to modulate the host response in vivo.