Bioinspired Glycopeptide Hydrogel Reestablishing Bone Homeostasis through Mediating Osteoclasts and Osteogenesis in Periodontitis Treatment
Zhezhe Zhao, Chenxuan Wu, Yini Huangfu, Yufeng Zhang, Ju Zhang, Pingsheng Huang, Anjie Dong, Yonglan Wang, Jiayin Deng, Weiwei Wang, Zujian Feng
Abstract
Irreversible alveolar bone resorption is one of the important clinical manifestations of periodontitis, which is initiated by a plaque biofilm and exacerbated by the imbalance of osteoclast activity and osteogenesis, affecting a patient’s masticatory function and resulting in a high recurrence rate of periodontitis. Herein, to reestablish bone homeostasis in periodontitis, a minocycline hydrochloride (MH)-loaded glycopeptide hydrogel (MH/GRW gel ) is fabricated to mediate alveolar bone absorption through sequential antibacterial and RANKL-blocking activities. GRW gel shows an ECM-like fibrous and porous microstructure serving as a scaffold for cell proliferation and differentiation and holds the merits including injectability, self-healing properties, and good biocompatibility. After injection in situ, MH is released rapidly from the hydrogel in the early stage, demonstrating a potent antimicrobial effect to combat the biofilm in the deep periodontal pocket. Moreover, MH/GRW gel exhibits a high specific binding efficiency with RANKL to suppress osteoclast maturation by shielding the RANKL/RANK interaction and enhancing osteogenic differentiation, thereby synergistically regulating bone homeostasis. In the rat periodontitis model, MH/GRW gel significantly curtails periodontitis progression through antimicrobial activity, inhibition of alveolar bone resorption, and promotion of bone regeneration, which is superior to the treatment of a commercial gel. These findings suggest that MH/GRW gel with superiority in regulating bone homeostasis provides a promising therapeutic strategy for periodontitis.