Immune modulation strategies to reduce in-stent restenosis

In-stent restenosis remains a significant complication following stent implantation, driven by complex interactions between immune responses, vascular injury, and inflammatory cascades. Despite advancements in stent technology, ISR persists, underscoring the need for innovative strategies to modulate immune activity and promote vascular healing. This review presents current knowledge on immune-mediated mechanisms of ISR, highlighting the pivotal roles of immune cell like neutrophils, macrophages in neointimal hyperplasia and chronic inflammation. We explore recent immunomodulatory approaches, including stent surface modifications, bioactive molecule delivery, and emerging technologies. Furthermore, we evaluate the clinical potential of next-generation stents such as endothelial-mimetic designs to mitigate ISR by balancing pro-reparative and anti-inflammatory signals. By integrating insights from preclinical and clinical studies, this review provides a new perspective for developing "immune-friendly" stents, emphasizing interdisciplinary strategies to attenuate ISR following stent implantation.