Granulocytes and their Involvement in the Foreign Body Response to Biomaterials and Tissue Repair

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Abstract
Granulocytes, long considered short-lived effector cells, are increasingly recognized as key modulators of the foreign body response (FBR) to biomaterials and determinants of regenerative outcomes. This review summarizes current evidence on the roles of neutrophils, basophils, and eosinophils in biomaterial-associated inflammation and tissue remodeling. Particular focus is placed on protein adsorption, cytokine release, and downstream effects across diverse biomaterial classes, including bone substitutes, collagen scaffolds, titanium, magnesium, and synthetic polymers. Neutrophils dominate the acute phase through reactive oxygen species, proteases, and neutrophil extracellular traps, which can either support remodeling or drive fibrosis and implant failure. Basophils, though rare, release histamine and Th2 cytokines, enhancing angiogenesis but also contributing to fibrotic encapsulation. Eosinophils are recruited in material-dependent patterns, releasing cytotoxic granules and pro-regenerative mediators, thereby functioning as double-edged regulators of degradation, fibrosis, and vascularization. Overall, granulocytes act as critical, though often overlooked, determinants of biomaterial integration. Incorporating granulocyte biology into biomaterial design–through modulation of surface chemistry, protein adsorption, and degradation kinetics– offers a promising path to guide inflammatory cascades toward constructive remodeling, angiogenesis, and predictable clinical performance.

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