A plasma-derived fibrin in situ hydrogel for sustained release of copper and zinc ions in periodontitis treatment.

The delayed healing of alveolar bone defects caused by periodontitis remains a thorny problem. Here, we developed a kind of natural hydrogel, Cu/Zn-FG, synthesized based on the formation of a hydrogel network triggered by thrombin and the coordination bond between the fibrin and metal ions. The characteristics of Cu/Zn-FG were evaluated using the following methods: morphological observation, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The anti-inflammatory effect and osteogenic differentiation potential of Cu/Zn-FG were also assessed on the RAW264.7 and MC3T3-E1 cells. Moreover, Cu/Zn-FG's in vivo therapeutic efficacy was evaluated in a rat model of periodontitis. The results demonstrated that Cu/Zn-FG could release copper and zinc ions for 26 hours as the protease activity increases in the infection microenvironment, and these ions can maintain their biological activity in vitro. Furthermore, we found that Cu/Zn-FG can effectively inhibit the growth activity of Porphyromonas gingivalis (P. gingivalis), promote osteogenic differentiation of MC3T3-E1 and regulate the expression of inflammatory factors of RAW264.7. In the process of the in vivo experiment, periodontitis rats treated with Cu/Zn-FG revealed that bone regeneration was accelerated. Our study confirms that Cu/Zn-FG is an innovative material that could promote alveolar bone regeneration in a rat model of periodontitis, exhibiting its translational potential for clinical application and providing a new therapeutic strategy in the treatment of periodontitis.