Gelatin methacryloyl-phenylboronic acid/Hydroxyadamantane self-healing microgels for the periodontitis treatment by promoting alveolar bone regeneration.

Periodontitis is a chronic inflammatory condition mainly caused by the interaction between the host immune system and periodontal tissue pathogens, and may lead to consequences, such as alveolar bone defects and tooth loss. Incomplete bacterial removal, persistent inflammation and high reactive oxygen species (ROS) environment are the main challenges for periodontal tissue repair and alveolar bone regeneration. In this study, an injectable composite microgel (Gelatin methacryloyl-Phenylboronic acid/Hydroxyadamantane, GPH) loaded with antimicrobial peptide (AMP) and cerium dioxide (CeO) microspheres was developed to achieve a synergistic function of bacteriostasis, immunomodulation, and ROS removal. In vitro studies had shown that the composite microgel had an inhibitory rate of >99 % against E. coli, S. aureus and P. gingivalis and scavenged DPPH with a rate of 87.1 % ± 2.0 %, exhibiting excellent antibacterial and antioxidant properties. In addition, it was able to promote macrophage phenotypic shift from M1-type to M2-type and reduce ROS levels, and also had excellent biocompatibility. Mechanistically, the composite microgel was subjected to transcriptome sequencing analysis of gene expression levels and signaling pathways in BMSC cells, and the results showed that the microgel played an important role in regulating the PI3K-Akt and chemokine signaling pathways, which in turn inhibited the expression of inflammatory factors. In vivo the effect of composite microgel on periodontal tissue repair and alveolar bone regeneration was verified by infected alveolar bone defect model. The results showed that after 4 weeks of using the composite microgel, the bone volume per unit of tissue volume of the alveolar bone, the thickness of bone trabeculae, and the bone mineral density reached 25.94 % ± 0.03 %, 0.14 mm ± 0.01 mm, and 0.442 g/cm ± 0.003 g/cm, respectively, while those of the control group were 22.3 % ± 0.29 %, 0.07 mm ± 0.02 mm, and 0.236 g/cm ± 0.059 g/cm, respectively, and the use of the composite microgel resulted in significantly better repair results than the control group. In addition, pro-inflammatory factors were significantly suppressed and inflammation levels were significantly reduced. Overall, this composite microgel showed great potential in reducing inflammation levels and promoting alveolar bone regeneration, providing an innovative approach to the treatment of periodontitis.