Bioinspired Microspheres For Periodontitis Therapy By Multi-Target Remodeling Microenvironment

Current treatments often fail to comprehensively achieve antimicrobial effect, inflammation control, and periodontal regeneration when treating with tortuous periodontal pockets and antibiotic-resistant bacteria. This study aims to develop bioinspired hydrogel microspheres capable of co-loading BMP9 and Berberine and provides a new strategy for the treatment of periodontitis. Microfluidics were used to prepare GelMA hydrogel microspheres equipped with PDA nanoparticles carrying Berberine and Ad-BMP9-stimulated PDLSCs. The physicochemical properties of microspheres are characterized using FTIR, UV-vis, SEM and gravimetric analysis. The antibacterial performance was evaluated through bacterial growth curves, live/dead bacterial dual staining, and bacterial biofilm crystal violet staining. The osteogenic and anti-inflammatory properties were examined using ALP, ARS staining and qPCR in vitro. Rat cranial defect and mouse periodontitis models were constructed to test anti-inflammatory and osteogenic characteristics in vivo. RNA sequencing was used to analyze the mechanisms of synergistic effects of BMP9 and Berberine in periodontitis. PDA/BBR@Gel@BMP9-PDLSC microspheres can slowly release Berberine and BMP9, exhibiting good physicochemical properties, biocompatibility and antimicrobial effect by inhibiting the growth of F.nucleatum. Microspheres can synergistically reduce inflammation and promote osteogenesis both in vitro and in vivo. The synergistic mechanisms of Berberine and BMP9 in enhancing bone formation and suppressing inflammation were achieved by regulating TGF-β, PPAR and TNF signaling pathways. This research presents a novel approach for comprehensively treating periodontitis by combining Berberine and BMP9 in a bioinspired delivery system, providing renewal of these two “traditional drugs” for improving disease prognoses.