In Vivo Assessment of SED: A Novel Biomechanical Indicator for Periodontal Tissue Remodeling in Clear Aligner Therapy

Orthodontic tooth movement fundamentally relies on force-driven remodeling of periodontal tissues. However, the therapeutic predictability of clear aligner therapy (CAT) remains limited, particularly in periodontal-compromised patients. This limitation stems from a critical gap between biomechanical loading and biological remodeling. This study innovatively adopts strain energy density (SED) as a biomechanical parameter to investigate the integrated biomechanical and biological responses of the periodontium to CAT.

We employed a cross-scale biomimetic framework that combined three-dimensional finite element modeling (FEM) with an in vivo rabbit model. Biological assays, including micro-CT, TRAP staining, immunohistochemistry, 4D proteomics, the Oroboros Oxygraph-2000 (O2K), and Western blot (WB), were conducted in SED-concentrated areas to elucidate SED-triggered biological cascades.

FEM quantified that periodontal SED escalated with attachment loss, concentrating at the labial alveolar crest. In vivo experiments indicated that elevated SED exacerbated periodontal damage, evidenced by reduced bone volume fraction and density, increased TRAP-positive osteoclasts, upregulated IL-1β, and downregulated BMP2. Proteomics identified 908 differential proteins in high-SED regions, which are enriched in NF-κB activation and suppression of oxidative phosphorylation. O2K and WB validated compromised mitochondrial complex I/II function, ATP production, and phosphate/oxygen ratio in these areas.

Using SED as a quantitative metric, this study bridges the biomechanical-biological gap by linking CAT-induced biomechanical responses to mitochondrial bioenergetic dysfunction. These findings establish a basis for a biologically informed predictive system to facilitate personalized CAT.