Cellular metabolic reprogramming in periodontitis: advanced therapeutic strategies and periodontal regeneration

Periodontitis is one of the most prevalent chronic inflammatory diseases worldwide, ultimately leading to tooth loss and masticatory dysfunction. Effective treatment of periodontitis requires not only control of inflammation but also regeneration of various cell types and tissues. Recent studies have shown that metabolic reprogramming in the periodontal microenvironment serves as a key link between inflammatory responses and an imbalance in bone homeostasis. Metabolic reprogramming not only drives disease progression but also profoundly influences tissue repair.

of review: This article provides a comprehensive review of metabolic reprogramming in immune cells and bone-related cells during periodontitis, with a particular focus on how metabolic abnormalities impair the osteogenic differentiation capacity of periodontal ligament stem cells and disrupt the balance between osteogenesis and osteolysis. Additionally, we highlight therapeutic strategies targeting metabolic pathways, especially those based on biomaterials, which can modulate the metabolism of immune cells and bone cells for periodontal regeneration. Finally, this review discusses future directions and emerging technologies in this field, aiming to offer theoretical support and clinical reference for a deeper understanding ofthe intricate interactive network of cell metabolism, immune response and bone remodeling and to develop precise strategies for periodontitis. Key scientific concepts of review: During periodontitis, distinct cell populations exhibit unique metabolic phenotypes: immune cells sustain inflammation via glycolysis, while bone-resident cells undergo metabolic shifts that impair their regenerative capacity. Restoring metabolic balance suppresses aberrant immunity, enhances bone formation, and creates a favorable microenvironment for periodontal regeneration. This review highlights emerging therapeutic strategies targeting metabolic pathways, particularly metabolism-modulating biomaterials. By integrating current advances, this review aims to elucidate the links among metabolism, immunity, and bone homeostasis, offering new directions for precise regenerative therapies in periodontitis.