A Novel Composite Hydrogel for Treating Periodontitis and Hypertension

Periodontitis and hypertension often occur as comorbidities. In the face of severe periodontitis patients with hypertension, periodontists often have to give priority to control the patient's blood pressure before surgical treatment, and how to use drugs also brings a lot of inconvenience for clinical treatment. In the stage of periodontal basic treatment, it is a problem that needs to be solved to treat periodontal inflammation and control blood pressure at the same time, so as to achieve “co-treatment of comorbidities”. To this issue, we proposed a controlled-release composite hydrogel approach with dual antibacterial and anti-inflammatory activities as a resolution for pathogen-originated periodontitis. Specifically, chitosan (CS) with inherent antibacterial properties was crosslinked with antimicrobial peptide (AMP) modified polyethylene glycol (PEG) to form the dual antibacterial hydrogel (CS-PA). Subsequently, curcumin nanoparticles (CNP) were encapsulated in the hydrogel to impart anti-inflammatory activities. In the mouse model of periodontitis complicated with hypertension, CS-PA/CNP was applied to gingival sulcus, found that it produced a perfect therapeutic effect on periodontitis and hypertension at the same time. The antibacterial experiments showed that CS-PA/CNP had an excellent inhibitory effect on a variety of periodontal pathogens, demonstrated the potential regulatory ability of the microbiota. In addition, cytological studies revealed the molecular mechanism that CS-PA/CNP enhanced antioxidant capacity of macrophages through the glutathione metabolism pathway, while enhancing their anti-inflammatory capacity. In conclusion, CS-PA/CNP has demonstrated its superior therapeutic effect and potential clinical translational value in the treatment of periodontitis and hypertension, which also serves as a drug delivery platform to provide combinatorial therapeutic options for periodontitis with complicated pathogenesis. Overall design: Comparative gene expression profiling analysis of RNA-seq data for BMDMs co-cultured with PgLPS or CS-PA/CNP