Nanomaterial-based strategies for anti-aging and regeneration in oral and maxillofacial tissues: Mechanisms and applications.

Abstract

The escalating global aging population underscores the urgent need to elucidate senescence-mediated tissue degeneration and impaired repair mechanisms, particularly in oral and maxillofacial regions where compromised regenerative capacity significantly affects quality of life. This review aims to synthesize current knowledge on how key pathological features of senescent microenvironment, including senescent cell accumulation, chronic inflammation, oxidative stress, and extracellular matrix (ECM) dysregulation, collectively establish self-perpetuating cycles that disrupt tissue homeostasis. Emerging evidence reveals the dual nature of senescence: while not merely dysfunctional entities, their dysregulation drives pathological ECM remodeling and metabolic dysfunction. Recent advances in functional nanomaterials have revolutionized approaches for precise microenvironment modulation. These engineered materials demonstrate multidimensional therapeutic capabilities, including spatiotemporal-specific senescent cell clearance through targeted biomarkers, intelligent ECM reconstruction via biomimetic nanostructures, dynamic immune homeostasis restoration, and metabolic network intervention. Notably, stimuli-responsive nanoplatforms that exploit senescence-associated microenvironmental alterations show particular promise for controlled therapeutic delivery. Despite significant progress, critical challenges remain in optimizing material biocompatibility and establishing standardized evaluation protocols for clinical translation. This review provides a comprehensive analysis of the senescent microenvironment in both oral and systemic aging processes, while evaluating design strategies for functional nanomaterials in microenvironment reprogramming, offering valuable insights for targeted interventions against senescence-associated oral pathologies and identifying priority research directions to address the growing challenge of oral tissue regeneration in aging populations.