An antioxidant, injectable hydrogel with mitochondrial fusion effect promotes inflamed dental pulp repair via immunomodulation and reactive oxygen species scavenging

Abstract

Vital dental pulp is crucial for the self-repair and long-term retention of teeth with pulpitis; pulp capping materials used for vital pulp therapy must involve controlling inflammatory cascade and regulating inflammatory microenvironment at the same time. Here, we designed a dual-effect hydrogel with immunoregulatory and antioxidant properties to achieve inflamed pulp tissue repair. MASM7, a "mitochondrial glue" promoting mitochondrial fusion, could modulate THP-1-derived macrophages (THP-1-M) polarization to the M2 type under LPS-stimulated inflammatory conditions. Seahorse assay and metabolic-flux analysis (MFA) revealed that mitochondrial fusion modulated metabolic reprogramming of THP-1-M under inflammation from glycolysis to OXPHOS. Moreover, MASM7-treated THP-1-M cells enhanced the repair ability of DPSCs under inflammatory conditions. To realize the application of MASM7 and antioxidant property, chitosan (CS) and methacrylic anhydride (MA) were used to synthesize a methacrylated CS (CSMA) hydrogel, which was then modified with gallic acid (GA) to form a CSMAGA hydrogel. We next confirmed the biocompatibility of this hydrogel. The CSMAGA hydrogel also demonstrated antioxidant properties by scavenging reactive oxygen species. We then confirmed the dual effects of MASM7@CSMAGA hydrogel in rats with LPS-stimulated pulpitis. In conclusion, MASM7@CSMAGA hydrogel can promote pulp tissue repair under inflammatory conditions by modulating macrophage polarization and oxidative stress.

Keywords: Antioxidation; Chitosan hydrogel; Immunoregulation; Macrophage polarization; Metabolic-flux analysis; Mitochondrial fusion.