Ann Marie Decker, Sandra Stuhr, Gustavo Avila‐Ortiz, Andrea Pilloni, Lorenzo Marini, Rogério M. Castilho, Beth Wallace, Yvonne Hernandez‐Kapila
OBJECTIVE: This narrative synthesizes current knowledge on the biological mechanisms, clinical challenges, and regenerative innovations for optimizing intraoral wound healing in the elderly. METHODS: Narrative review of preclinical and clinical studies addressing age-related changes in the four canonical wound-healing phases (hemostasis, inflammation, proliferation, remodeling), tissue-specific molecular pathways, systemic and local factors affecting repair, operative considerations, and emerging therapeutic modalities. Data sources included PubMed, Embase, and Cochrane databases through June 2025. RESULTS: Aging compromises each repair phase. Hemostasis is prolonged by diminished platelet function and altered clot architecture. Inflammation is exacerbated by impaired neutrophil/phagocyte activity and persistent reactive oxygen species. Proliferation is slowed by reduced fibroblast proliferation and angiogenic signaling, while dysregulated matrix metalloproteinase activity impairs extracellular matrix remodeling. Tissue-specific cues in oral mucosa, periodontal ligament, cementum, and bone are also altered with age. Compounding factors-including "inflamm-aging," malnutrition, polypharmacy-induced xerostomia, cognitive decline, and frailty-further impede healing. Clinical optimization requires comprehensive preoperative risk and frailty assessments; medical/nutritional management; minimally invasive flap designs; tension-free primary closure; streamlined surgical protocols to limit operative time; and postoperative monitoring with tailored communication. Emerging regenerative strategies-growth factors (PDGF, FGF), platelet concentrates, gene and cell-based approaches (MSCs, exosomes), immunomodulatory scaffolds/agents, photobiomodulation, and AI-driven risk dashboards-show promise for enhancing repair in aging populations. CONCLUSIONS: Effective oral wound healing in older adults demands a multidisciplinary, personalized approach that integrates meticulous perioperative care with novel regenerative modalities. Standardization and clinical validation of emerging therapies are essential to translate biological insights into improved patient outcomes.