Adhesive Microneedle‐Nanosheets With Temporally Orchestrated Antimicrobial, Immunomodulatory, and Osteogenic Functions for Periodontal Regeneration

An ideal guided bone regeneration (GBR) membrane must simultaneously maintain structural rigidity and adhesive properties for early space stabilization, defense against bacteria, efficiently manage inflammation and thus promote periodontal regeneration. Herein, we engineer a novel microneedle-nanosheet (MN) composite membrane that enables conformal adhesion to bone surfaces and sequentially targets the bacterial and inflammatory phases in periodontitis (PD). Upon implantation, with the instant degradation of the polyvinyl alcohol (PVA) layer, MN achieves adaptive adhesion to periodontal defect sites via nanoscale properties. Accelerated degradation of gelatin methacryloyl (GelMA) layer enables sustained antimicrobial peptide release to control periodontal pathogens, while slow degradation of microneedle facilitates sustained delivery of mesenchymal stem cell-derived exosomes. In vitro, MN exhibits favorable mechanical stability, potent antibacterial activity against periodontal pathogens, biocompatibility, and promotes osteogenesis/angiogenesis. In rat and beagle dog periodontal bone defect models, MN enhances immunomodulation, osteogenesis, and angiogenesis, resulting in significant alveolar bone regeneration. 16S rRNA sequencing reveals reduced abundance of PD-associated bacterial communities, while RNA sequencing analysis further demonstrates activation of immune signaling pathways. In summary, MN adapts to critical demands for next-generation GBR membranes that offer a dynamic, bio-integrated microenvironment for tissue healing and regeneration by enabling temporally regulation, from space maintenance to multiplexed biological functions.