Harnessing neutrophils for tissue repair and regeneration: mechanisms, biomaterial engineering strategies and translational potential.

Tissue injury disrupts structural integrity and physiological homeostasis, triggering inflammatory and reparative responses that determine whether healing results in regeneration or fibrosis. Increasing evidence indicates that effective tissue restoration depends not only on the intrinsic regenerative potential of resident or transplanted cells but also on the spatiotemporal coordination of immune regulation, extracellular matrix remodeling and local microenvironmental signaling. Among immune populations, neutrophils are emerging as pivotal regulators of tissue repair rather than merely short-lived antimicrobial effectors. As the earliest leukocytes responding to injury, they rapidly sense inflammatory cues, traffic to injured tissues and shape the early regenerative niche through phagocytic clearance, reactive oxygen species-dependent and -independent effector functions, neutrophil extracellular trap formation and crosstalk with immune and structural cells. Their marked heterogeneity and phenotypic plasticity further expand their roles in determining repair outcomes. This review highlights how the distinctive biological properties of neutrophils are being translated into emerging engineering and therapeutic strategies, including neutrophil-inspired biomaterials, biomimetic delivery systems and immunomodulatory interventions. Current challenges in precise regulation, biosafety and clinical translation are also discussed. Collectively, neutrophils are positioned as both key immune regulators and promising bioinspired targets for next-generation regenerative medicine.