Biomimetic‐Engineered Hydrogels Prevent Orthodontic Root Resorption

Abstract Orthodontically induced inflammatory root resorption (OIIRR) is one of the most common complications in dentistry. It is considered irreversible and harmful to tooth integrity. The narrow, irregular morphology and complex, layered structure of periodontal and periapical tissues, combined with a potentially bacteria‐laden inflammatory environment, make treatment and prevention an immense challenge. This study presents a biomimetic‐engineered thermoresponsive hydrogel with distinct physicochemical properties that serves as a biological scaffold to support the growth and differentiation of periodontal ligament stem cells (PDLSCs), while maintaining optimal flow for injectability and diffusion. Additionally, it provides strong antibacterial protection and excellent biocompatibility, allowing in vivo tracking of stem cells. Furthermore, it mimics the native stem cell niche, with slow‐release rapamycin inducing autophagy and orchestrating cascades that modulate adipogenic and osteogenic differentiation, mechanical stress response, migration, redox homeostasis, inflammation, and stress adaptation. This enables encapsulated PDLSCs to thrive even in inflammatory, stressful environments, preventing excessive resorption in the periodontal‐apical complex in an animal model. This innovative approach pioneers a new frontier in the prevention of root resorption, offering a potential game‐changer for dentistry. The hydrogel design further opens exciting possibilities for regenerative treatments targeting other systemic inflammatory diseases.