Molecular Pathways of Macrophage Polarization

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Introduction. Macrophage polarization is a key mechanism of immune regulation that determines their functional plasticity. Depending on the microenvironment, macrophages differentiate into proinflammatory (M1, activated by IFN-γ and LPS) or anti-inflammatory (M2, stimulated by IL-4 and IL-13) phenotypes. The article analyzes the molecular mechanisms of polarization, including signaling pathways (JAK-STAT, NF-κB, PPAR-γ) and metabolic shifts (glycolysis, oxidative phosphorylation). These processes open up prospects for managing inflammation and regeneration, which is important for the development of biomaterials with anti-inflammatory properties. Objective. The purpose of this review is to systematize current data on the mechanisms of macrophage polarization to develop strategies for controlling their activity in the context of creating functional biomaterials. Material and methods. The search for scientific sources in the PubMed, GoogleScholar, and eLibrary databases was carried out for the period 2008 – 2024. A total of 1,469 scientific sources were found. Based on the analysis of novelty, depth of study of the topic, and citation, 68 articles were selected (after excluding duplicate publications) that most fully reflect modern concepts of: classical and alternative activation of macrophages, the role of metabolic rearrangements, and epigenetic regulation. Conclusion. Modern research reveals the complex molecular mechanisms underlying macrophage polarization. This process involves fine-tuning of signaling pathways, epigenetic modifications, and metabolic reprogramming that determine their phenotypic plasticity, which plays a key role in maintaining the balance between inflammation and regeneration. Managing macrophage polarization opens up new prospects for controlling the immune response and tissue regeneration, which is especially relevant for the development of biomaterials and implants. Their unique ability to transform makes macrophages central regulators of both physiological homeostasis and pathological processes.