Cold Atmospheric Plasma Combined with Nucleoside‐based Hydrogel Facilitates Extraction Socket Healing in Minipigs

Abstract Tooth extraction is one of the most common dental surgery and is often associated with multiple complications that can impair both aesthetic and functional rehabilitation of the patients. Complete healing of extraction sockets remains challenging due to the complexity of the oral environment. In this work, cold atmospheric plasma (CAP) combined with 2‐amino‐2′‐fluoro‐2′‐deoxyadenosine (2‐FA) nucleoside‐based supramolecular hydrogel demonstrates the potential to expedite the extraction socket healing in minipigs by promoting rapid hemostasis and enhancing healing in both soft and bone tissues. A new CAP device designed for oral cavities could generate multiple long‐lived reactive oxygen and nitrogen species (RONS) that persist for over 24 h and facilitate hemostasis in three bleeding models. Moreover, CAP induces M2 differentiation of macrophages and activation of gingival fibroblasts through the NRF2 antioxidant pathway. Collectively, the combination of CAP and 2‐FA results in accelerated soft tissue sealing and complete bone healing in rat and minipig extraction wounds, outperforming commercially available hemostatic materials gelatin sponges. This combined approach presents a promising strategy for promoting the recovery of extraction socket wounds and holds significant potential for clinical application.