Strontium-incorporated thermoresponsive hydrogel platform co-delivering graphene oxide-mannose nanocomplexes: An osteoimmunomodulatory strategy for periodontitis therapy

Abstract

Periodontitis is an immune-mediated disease that destroys tooth-supporting tissues, yet existing treatments cannot synchronize inflammation resolution with bone regeneration. To address this unmet need, we report an injectable, strontium-incorporated an injectable thermoresponsive hydrogel (composed of chitosan, 0.6% gelatin, and β-glycerophosphate) platform engineered for the delivery of graphene oxide-mannose nanocomplexes (designated GM-Sr@Hydrogel). Upon injection, this platform undergoes rapid thermoresponsive stiffening, enabling the localized and controlled release of Sr2+ and GO-DM nanocomplexes within the periodontal microenvironment. The osteoimmunomodulatory capacity of this system was rigorously evaluated in a ligature-induced periodontitis model in vivo and further dissected using an in vitro inflammatory and osteogenic co-culture system. Our results demonstrate that the GM-Sr@Hydrogel functions as a potent osteoimmune regulator, evidenced by significant attenuation of periodontal inflammation and robust preservation of alveolar bone mass. Mechanistically, in vitro, this multifunctional platform concurrently promotes the osteogenic differentiation of periodontal ligament cells (PDLCs), restrains their pathological inflammatory activation, and impairs the maturation trajectory of dendritic cells (DCs) in a pro-inflammatory niche. Collectively, these findings delineate a novel osteoimmunomodulatory strategy for preserving periodontal homeostasis and establish the GM-Sr@Hydrogel as a promising translational platform for the management of periodontitis.