3D-printed bioink loading with stem cells and cellular vesicles for periodontitis-derived bone defect repair.

The suitable microenvironment of bone regeneration is critically important for periodontitis-derived bone defect repair. Three major challenges in achieving a robust osteogenic reaction are the exist of oral inflammation, pathogenic bacteria invasion and unaffluent seed cells. Herein, a customizable and multifunctional 3D-printing module was designed with GMA modified epsilon-poly-L-lysine (EPLGMA) loading periodontal ligament stem cells (PDLSCs) and myeloid-derived suppressive cells membrane vesicles (MDSCs-MV) bioink (EPLGMA/PDLSCs/MDSCs-MVs, abbreviated as EPM) for periodontitis-derived bone defect repair. The EPM showed excellent mechanical properties and physicochemical characteristics, providing a suitable microenvironment for bone regeneration. In vitro, EPMs presented effectively kill the periodontopathic bacteria depend on the natural antibacterial properties of the EPL. Meanwhile, MDSCs-MV was confirmed to inhibit T cells through CD73/CD39/adenosine signal pathway, exerting an anti-inflammatory role. Additionally, seed cells of PDLSCs provide an adequate supply for osteoblasts. Moreover, MDSCs-MV could significantly enhance the mineralizing capacity of PDLSCs-derived osteoblast. In the periodontal bone defect rat model, the results of micro-CT and histological staining demonstrated that the EPM scaffold similarly had an excellent anti-inflammatory and bone regeneration efficacy in vivo. This biomimetic and multifunctional 3D-printing bioink opens new avenues for periodontitis-derived bone defect repair and future clinical application.