In Vitro Modulation of Macrophage Inflammatory and Pro-Repair Properties Essential for Wound Healing by Calcium and Calcium-Alginate Dressings

Macrophages participate in cutaneous wound healing by adopting M1 pro-inflammatory and M2 immunoregulatory/pro-repair phenotypes. Chronic wounds associated with a deficient macrophage response could benefit from treatments that restore an acute inflammatory response and promote healing. Calcium-alginate dressings release calcium ions, which are potent bioactivators of macrophage function in wounds. Here, the effects of two calcium-alginate dressings, Algosteril^® (ALG, pure Ca²⁺ alginate) and Biatain^® Alginate (BIA, Ca²⁺ alginate with carboxymethyl cellulose), and a 3 mM CaCl₂ solution were compared in human macrophages polarized to M1 or M2. ALG and CaCl₂ preserved monocyte viability, and BIA reduced it. Both alginates and CaCl₂ reinforced the M1 pro-inflammatory transcriptional profile and phenotype, with significant increases in IL-6 and TNF-α secretion by ALG only. In M2 macrophages, all conditions increased the M1-specific gene expression and reduced M2 markers, suggesting an orientation toward an inflammatory profile. Only ALG significantly increased the secretion of CCL18 and VEGF, suggesting pro-repair activity. All conditions increased M2 phagocytic activity. This work demonstrates the interest in calcium alginates for stimulating macrophage subtypes, which could help restore wound healing, especially in patients with compromised innate immunity. It highlights the differences among the calcium-alginate dressings. The pure alginate shows higher stimulation of macrophage pro-inflammatory and pro-repair functions.