Dental cementum anchored microspheres embedded in a self-healing hydrogel for the antibacterial, anti-inflammation, osteogenic, and anti-osteoclastic management of periodontitis disease.

Periodontitis, a prevalent chronic oral disease, poses a significant threat to periodontal tissues, often resulting in substantial attachment loss and tooth shedding. Leveraging the principles of bone affinity and the mechanism underlying tetracycline pigmentation of teeth, this study strategically employed tetracycline (TC) as a bone-affinity group. We modified TC on the surface of polylactic-co-glycolic acid copolymer (PLGA) microspheres (MSs) through covalent binding, and then loaded berberine (BBR) MSs into a thermosensitive self-healing hydrogel delivery system (BBR/TC-MS). It was verified that the BBR/TC-MS gel rapidly formed an in situ reservoir in the periodontal pocket upon injection, and the chelation between TC and cementum in the periodontal pocket enhanced the anchoring effect of the TC-modified microspheres on cementum, preventing their loss through gingival crevicular fluid. Subsequently, we proved in vitro and in vivo that the BBR/TC-MS gel has excellent bacteriostatic effects against the periodontal pathogenic bacteria Fusobacterium necrophorum (Fn), anti-inflammation property in periodontal and gingival tissues, and osteogenic effect by regulating the RANKL-RANK-OPG pathway to diminish osteoclast activity, thus continuously exerting antibacterial, anti-inflammatory, osteogenic, and anti-osteoclastic effects. This innovative approach holds promise as a targeted and effective strategy for combating multifaceted challenges posed by periodontitis.