A plasma-derived fibrin <i>in situ</i> 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 <i>in vivo</i> 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 <i>in vitro</i>. Furthermore, we found that Cu/Zn-FG can effectively inhibit the growth activity of <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), promote osteogenic differentiation of MC3T3-E1 and regulate the expression of inflammatory factors of RAW264.7. In the process of the <i>in vivo</i> 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.