Nitric Oxide in Biomaterial-Based Therapies for Coronary Heart Disease: Mechanistic Insights, Current Advances, and Translational Prospects

Coronary heart disease (CHD) remains a leading etiology of cardiovascular mortality globally. Endothelial dysfunction is now well-documented as the incipient pathological event in coronary atherosclerosis, with endogenous nitric oxide (NO) and nitric oxide synthase playing pivotal roles in regulating endothelial homeostasis via diverse signaling cascades. Over the past several decades, the pleiotropic functions of NO in cardiovascular physiology and pathophysiology have sparked substantial research interest in leveraging exogenous NO delivery strategies for atherosclerotic interventions. Beyond conventional NO-based pharmacotherapies, notable advancements have been achieved in the development of NO-releasing platforms and donor systems capable of spatiotemporally controlled and sustained NO delivery to target vascular tissues. This comprehensive review synthesizes current understanding of (a) the dual roles of endogenous NO in maintaining cardiovascular health and mediating pathological processes, (b) the enzymatic regulation of NO biosynthesis and its downstream signaling networks, and (c) the emerging translational potential of NO-based biomaterials in atherosclerotic management. Particular emphasis is placed on evaluating novel NO-donor systems and bioengineered constructs that exhibit therapeutic efficacy in preclinical models. Collectively, this analysis underscores the critical importance of NO-based biomaterials in advancing precision medicine approaches for CHDs, with implications for both diagnostic innovation and therapeutic optimization.