A Multi-Functional Microneedle Patches For Periodontal Regeneration

Periodontitis is a chronic inflammatory disease initiated by bacteria, which is the leading cause of tooth loss. Clinically, barrier membrane is used to guided tissue regeneration (GTR) for alveolar bone repair. However, the commercial membrane is hard to effectively achieve periodontal regeneration. Here, we fabricated a novel multifunctional nanosheets loaded with antimicrobial peptide Tet-213 and human mesenchymal stromal cells (hMSCs) derived exosomes. The polyvinyl alcohol (PVA) nanosheets served as the sacrificial layer, while the poly(caprolactone) (PCL) nanofibers layer was coated as barrier layer to resist epithelial invasion using the spin-coating technique. Then the third layer was composed of hydrophilic gelatin methacryloyl (GelMA) loaded with Tet-213, and GelMA solution carrying exosomes was directly formed into the integrated microneedle patches (MNPs) by 3D printing technology. In vitro experiments confirmed that the MNPs had good antibacterial properties and exhibited anti-inflammatory effect by inducing M2 polarization of macrophages, while promoting osteogenic differentiation and tube formation of mouse bone mesenchymal stromal cells (mBMSCs). Furthermore, in vivo experiments confirmed that MNPs shows an excellent influence on anti-bacteria, anti-inflammatory, and bone regeneration, which could effectively achieve periodontal bone repair. Mechanistically, RNA sequencing (RNA-seq) analysis revealed that MNPs’ differentially expressed genes were mainly enriched in immune regulation, cell differentiation and angiogenesis related pathways. In conclusion, we have successfully constructed a microneedle nanofilm material, which may be expected as a novel strategy for deep drug delivery for promoting periodontal regeneration in the future.