Light‐Responsive Surface Topographies Modulate Macrophage Immune Responses Through Dynamic Mechanical Cues

Understanding macrophage phenotype regulation by mechanical stimuli is a promising way to elucidate the body's inflammatory response and design new therapies. However, creating dynamic interfaces that allow precise, real-time, and reversible control over mechanical cues remains a challenge. In this study, we report the immunomodulatory effects of dynamic liquid crystal (LC) polymer films on in vitro macrophage responses. By utilizing reversible light-induced LC surface topographies, we generate dynamic mechanical stimuli on cells during topography formation and removal, enabling on-demand and reversible reprogramming of cell behavior. Our findings reveal a strong topographical shape-dependent cell response by examining the effects of flat, pillared, and grooved LC films on THP-1-derived macrophages. A strong increase in both pro- and anti-inflammatory markers is observed on grooves, while pillars maintain the anti-inflammatory profile without broad activation. Macrophages on LC film-generated topographies furthermore present distinct cytokine expression profiles. Notably, light-induced grooves triggered a stronger pro-remodeling cellular response, while pillars appeared to exert an inhibitory effect on macrophage activation. The dynamic topographies remarkably induced distinct changes in the macrophage membrane morphology, triggering migration-associated blebbing of the cell membrane in all cases except for grooves that promoted an increased degree of lamellipodia and filopodia formation. Overall, these results demonstrate that light-responsive LC surfaces provide a controllable platform for topography-dependent and adaptive immune modulation, opening opportunities for rational design of immunoregulatory scaffolds that exploit macrophage plasticity for regenerative medicine.