A multifunctional injectable microsphere with enhanced near-infrared photo-antibacterial, ROS scavenging, and anti-inflammatory properties for periodontitis treatment.

Background: Pathogenic bacteria and activated immune cells in periodontal tissues continuously generate reactive oxygen species (ROS) and inflammatory mediators, creating an oxidative stress microenvironment that causes damage to cells and tissues. Antimicrobial strategies and ROS scavenging are crucial for treating periodontitis. Methods: This study encapsulated iron-curcumin nanoparticles (Fe-Cur NPs) within GelMA microspheres using microfluidic technology. The microsphere surface was then modified with a polydopamine (PDA) layer, and minocycline hydrochloride (MH) was attached to it to form multifunctional composite microspheres (GM@Fe-Cur/PDA/MH). Results: The GM@Fe-Cur/PDA/MH microspheres exhibited excellent adhesion, allowing them to remain in periodontal pockets for prolonged periods to maintain their functionality. Benefiting from the photothermal properties of PDA combined with MH, these microspheres effectively kill bacteria and mitigate excessive immune responses. Additionally, they regulate the M1/M2 polarization of macrophages, suppress the expression of inflammatory factors, and promote osteogenic protein expression under oxidative stress conditions in vitro. In a rat model of periodontitis, GM@Fe-Cur/PDA/MH effectively controlled inflammation progression and reduced alveolar bone loss. Further studies indicated that GM@Fe-Cur/PDA/MH may promote ROS scavenging by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway while inhibiting the activation of the nod-like receptor protein-3 (NLRP3) inflammasome. Conclusions: In summary, GM@Fe-Cur/PDA/MH represents an effective therapeutic approach that integrates antibacterial, antioxidant, anti-inflammatory, and bone loss mitigation properties, demonstrating significant potential for application in the treatment of periodontitis.