A novel calcium alginate hydrogel formulation to enhance monocyte/macrophage anti-inflammatory activity

Alginate hydrogels are biocompatible and present tunable properties making them ideal for biomedical applications. We designed a novel Ca²⁺-Alginate hydrogel and investigated its bioactivity on key component of the immune inflammatory process, the monocytes/macrophages. Our results demonstrate that the developed Ca²⁺-Alginate hydrogel downregulated the expression of inflammation-related markers CD36 and CD64, in both classical and intermediate monocyte subsets. Additionally, the hydrogel upregulated the expression of the anti-inflammatory marker CD206 in both subsets and reduced their capacity to produce TNFα. In macrophages, the hydrogel modulated the pro-inflammatory M1 towards an anti-inflammatory profile, as evidenced by an increased population of CD163⁺CD206⁺ macrophages, typically associated with anti-inflammatory/immunoregulatory activity, and a decreased production of TNFα. The hydrogel also affected mitochondrial function in M1-macrophages, increasing mitochondrial mass and reducing reactive oxygen species production. The translational potential of the hydrogel was evaluated on circulating monocytes from patients suffering from the severe skin disease recessive dystrophic epidermolysis bullosa. The hydrogel increased the anti-inflammatory classical monocyte subset at the expense of the intermediate inflammatory subset. It also reduced CD36 and CD64, and downregulated TNFα production. Collectively, our findings provide evidence of the anti-inflammatory potential of a Ca²⁺-Alginate hydrogel, suggesting its promising therapeutic application to modulate inflammation.