Constructing biocompatible MSN@Ce@PEG nanoplatform for enhancing regenerative capability of stem cell via ROS-scavenging in periodontitis

Abstract The excessive local reactive oxygen species (ROS) level of periodontitis results in the quantity and function decline of periodontal ligament stem cells (PDLSCs), which aggravates the destruction and impedes the restoration of periodontal tissue. Therefore, regulating and restoring local ROS levels may promote stem cell survival and function recovery, improving periodontal tissue regeneration. Thus, protecting PDLSCs from oxidative stress injury and promoting regenerative capacity are both important. In this study, we synthesized a simple multi-functional nanocomposite by loading ceria oxide (CeO2) onto the surface of mesoporous silica (MSN@Ce), and then modified them with PEG (MSN@Ce@PEG) for better dispersion and biocompatibility, achieving simultaneous intracellular ROS-regulation and osteogenic differentiation promotion for PDLSCs against oxidative stress in periodontitis. We investigated the in-vitro regulatory effects of MSN@Ce@PEG NPs in hPDLSCs with H2O2-induced oxidative stress injury and the in-vivo therapy effects in a rat model of oxidative stress-induced periodontal disease, as well as the potential biotoxicity. Results have demonstrated that MSN@Ce@PEG NPs have good biocompatibility, and also showed MSN@Ce@PEG NPs not only efficiently regulated intracellular ROS, which protected cells from aging and improved the differentiative capacity of hPDLSCs, but also prevented inflammatory destruction of periodontal tissue. MSN@Ce@PEG NPs have great potential in ROS-regulation for safe and efficient periodontal therapy and are expected to be applied in other biomedical fields associated with redox metabolism imbalance.