Construction of versatile fibroin/nanozyme hybrid microneedles with controllable phototherapeutic sterilization property against periodontitis

Periodontitis is a highly prevalent disease that affects up to 90% of the worldwide population. The highly dynamic oral environment, tissue-teeth "pocket" structure, and antimicrobial resistance pose challenges to periodontitis local treatments, which urgently need to be upgraded with advanced biomaterials and novel therapeutics. Herein, a new treatment strategy for periodontitis is proposed by synergistic nanozyme catalyzed phototherapeutic/chemodynamic sterilization and microneedles (MNs) in situ delivery platform. A biodegradable versatile photothermal microneedles (MN-SF/CuS) patch was constructed by the in situ growth of monodispersed ultrasmall CuS nanozyme on silk-fibroin (SF) biomolecule and then hybridization in methacrylated hyaluronic acid (HAMA). The synthetic SF/CuS nanozyme endows microneedles with amplifies phototherapeutic/chemodynamic sterilization, excellent mechanical properties, and promotes periodontal tissue regeneration. The constructed MN-SF/CuS can be conveniently and minimally invasively inserted deeply into periodontal tissue without being affected by saliva, where it delivers thermal action, reactive oxygen species, and copper to the specified depth, achieving rapid sterilization and inhibition of bacterial growth. Meanwhile, MN-SF/CuS achieves on-demand phototherapy effect without damaging surrounding normal tissues. A preclinical large animal model confirmed that the MN-SF/CuS provided excellent irreversible antibacterial activity and promoted tissue regeneration, substantially improving the tolerance and compliance of periodontal treatment.