The effect of the physicochemical properties of hydrogels on chronic inflammation by macrophage polarization

By precisely controlling the mechanical and physicochemical properties of hydrogels, it is possible to directionally remodel the immune microenvironment, providing a key strategy for the treatment of chronic inflammation. Macrophages, as central regulators in the immune microenvironment, have attracted attention for their important roles in regulating cytokines. Their functional state is largely dependent on the phenotypic polarization between classically activated pro-inflammatory (M1) type and alternatively activated anti-inflammatory/pro-repair (M2) type. This review focuses on how the key physicochemical properties of hydrogels (stiffness, pore size, viscoelasticity, degradation rate, surface charge, hydrophilicity, and hydrophobicity) can systematically regulate the M1/M2 phenotype polarization behavior of macrophages. A deep understanding of the physicochemical properties of hydrogels and their interactions with macrophages provides an important foundation for the design of immunomodulatory biomaterials. Furthermore, based on the aforementioned physicochemical properties, this paper explores the specific applications of immunomodulatory hydrogels in anti-inflammatory therapy, particularly their latest research progress and application prospects in the treatment of diabetic ulcers, atopic dermatitis, and hypertrophic scars, aiming to provide new insights and methods for future tissue engineering and clinical translation.