Magneto-Actuated Antioxidative Lignin@Fe3O4 Nanoclusters to Decorate a Polyelectrolyte Scaffold for Macrophage Manipulation via Mechano-Chemo Coordination

Successful tissue remodeling following biomaterial implantation requires adequate tissue integration, which is often compromised by macrophage-mediated foreign body responses and persistent inflammation. Developing biomaterials that actively modulate macrophage behavior via biophysical and biochemical cues holds significant promise for tissue engineering. Here, we present a magneto-actuated polyelectrolyte scaffold platform, where antioxidative lignin@Fe3O4 nanoclusters are noncovalently anchored onto chitosan/chondroitin sulfate scaffolds. Upon exposure to a dynamic magnetic field, the nanoclusters generate interfacial microvibrations, delivering dynamic mechanical stimuli to macrophages while simultaneously scavenging reactive oxygen species via their intrinsic antioxidative activity. This mechano-chemo coordinated modulation effectively induces macrophage polarization from the M1 to M2 phenotype, as evidenced by significantly downregulated pro-inflammatory markers and upregulated anti-inflammatory markers in vitro. As a proof of concept, the subcutaneous implantation of scaffolds under the dynamic magnetomechanical actuation demonstrates improved tissue integration, characterized by reduced inflammation and enhanced extracellular matrix deposition. This platform offers an approach for promoting biomaterial adoption and tissue remodeling through spatiotemporally coordinated mechano-chemo modulation.