Surface-Induced Mechano-Regulation of Macrophages: Emerging Strategies for Immunotherapy

Surface mechanical regulation is emerging as a powerful strategy for programming macrophage behavior, which is crucial for next-generation immunotherapies and regenerative medicine. Mechanical cues such as stiffness, viscoelasticity, roughness, and micro-/nano-patterning on material surfaces can modulate macrophage functions by affecting cytoskeletal tension, nuclear mechanics, and chromatin accessibility. These cues can induce lasting phenotypic and epigenetic changes, allowing precise control over macrophage programs that are pro-regenerative, anti-inflammatory, or antitumor. The review highlights the potential of mechano-bioengineered platforms to reshape the immune microenvironment and discusses challenges like in vivo mechanical stability and long-term biocompatibility. Advances in AI and computational design are enhancing the development of personalized mechanoregulatory surfaces, paving the way for new clinical applications in disease treatment and tissue regeneration.