Mechanical polarity as a driver of bone regeneration: a multiscale framework linking tension, mechanotransduction and...

Mechanical loading is a fundamental regulator of bone remodeling, yet most conceptual models still focus on the magnitude of strain rather than its polarity. Here we propose a unified mechanobiological framework in which tensile-strain-dominant microenvironments act as primary drivers of cortical bone apposition, whereas compression-dominant fields predispose tissues to resorption and structural thinning. We synthesize evidence from long-bone bending, distraction osteogenesis, craniofacial suture biology, osteocyte mechanotransduction, and the periodontal ligament-alveolar complex to show that tensile strain consistently correlates with angiogenic activation, osteoblast lineage recruitment, and matrix deposition. We illustrate how subtle changes in load direction and boundary conditions can invert strain polarity in cortical regions that are classically considered "at risk" under bending or transverse displacement. We integrate these mechanical observations with canonical signaling pathways to outline a multiscale law of tension-guided bone adaptation and propose testable predictions for regenerative strategies. This perspective reframes bone mechanobiology around strain polarity and provides a conceptual scaffold for designing load-based interventions that exploit tensile fields to drive cortical regeneration across skeletal sites.