Shaping the immune landscape: Multidimensional environmental stimuli refine macrophage polarization and foster revolutionary approaches in tissue regeneration

In immunology, the role of macrophages extends far beyond their traditional classification as mere phagocytes; they emerge as pivotal architects of the immune response, with their function being significantly influenced by multidimensional environmental stimuli. This review investigates the nuanced mechanisms by which diverse external signals ranging from chemical cues to physical stress orchestrate macrophage polarization, a process that is crucial for the modulation of immune responses. By transitioning between pro-inflammatory (M1) and anti-inflammatory (M2) states, macrophages exhibit remarkable plasticity, enabling them to adapt to and influence their surroundings effectively. The exploration of macrophage polarization provides a compelling narrative on how these cells can be manipulated to foster an immune environment conducive to tissue repair and regeneration. Highlighting cutting-edge research, this review presents innovative strategies that leverage the dynamic interplay between macrophages and their environment, proposing novel therapeutic avenues that harness the potential of macrophages in regenerative medicine. Moreover, this review critically evaluates the current challenges and future prospects of translating macrophage-centered strategies from the laboratory to clinical applications.