Recent Advances in Periodontal Regenerative Medicine: A Focus on the Role of Mechanical Stimulation.

Periodontitis is a prevalent chronic inflammatory disease that leads to the progressive destruction of periodontal tissues and remains the primary cause of tooth loss worldwide. Despite advances in regenerative approaches-including stem cell therapy, scaffold-based tissue engineering, and guided tissue regeneration-the complete and functional restoration of the periodontal ligament remains a major clinical challenge. Stem-cell-based therapies and advanced biomaterials have emerged as promising strategies in regenerative medicine, offering potential for restoring periodontal structure and function. Among cells, periodontal-ligament-derived stem cells (PDLSCs) show exceptional regenerative potential due to their ability to differentiate into cementoblasts, osteoblasts, and other cell types essential for periodontal repair. In recent years, a variety of biomaterials with distinct specifications and properties have been utilized to repair periodontal damage. In addition to the inherent properties of biomaterials, the morphology and structural characteristics of these materials as bioequivalents for periodontal regeneration are also critical considerations. Furthermore, recent studies emphasize that mechanical stimulation plays a considerable role in directing stem cell differentiation, gene expression, matrix organization, and modulating inflammatory responses in periodontal regeneration. Canonical parameter ranges for systematic analysis indicate that cyclic stretch strain of 1-20% at 0.1-0.5 Hz (6-30 cycles/min) typically increases the expression of osteogenic markers (RUNX2, ALP, OCN) and matrix components (Col1) in PDLSCs. Conversely, higher values (>15%) often bias the response toward inflammatory pathways (IL-6, PGE2). Static compression above 2 g/cm