Insufficient angiogenesis frequently occurs after the implantation of orthopedic materials, which greatly increases the risk of bone defect reconstruction failure. Therefore, the development of bone implant with improved angiogenic properties is of great importance. Mimicking the extracellular matrix clues provides a more direct and effective strategy to modulate angiogenesis. Herein, inspired by the bioelectrical characteristics of the bone microenvironment, a piezoelectric bioactive glasses composite (P‐KNN/BG) based on the incorporation of polarized potassium sodium niobate is constructed, which could effectively promote angiogenesis. It is found that P‐KNN/BG has exceptional wireless electrical stimulation performance and sustained active ions release. In vitro cell experiments reveal that P‐KNN/BG enhances endothelial cell adhesion, migration, and differentiation via activating the eNOS/NO signaling pathway, which might be contributed to cell membrane hyperpolarization induced by wireless electrical stimulation increase the influx of active ions into the cells. In vivo chick chorioallantoic membrane experiment demonstrates that P‐KNN/BG shows excellent pro‐angiogenic capacity and biocompatibility. This work broadens the current understanding of bioactive materials with bionic electrical properties, which brings new insights into the clinical treatment of bone defect repair.

IntroductionThis study aimed to investigate the effect of Stat3 on the osteoblast‐mediated bone healing in the inflammatory lesion.MethodsThe conditional knockout of Stat3 in osteoblasts (Stat3 CKO) was generated via the Cre‐loxP recombination system using Osterix‐Cre transgenic mice. The calvarial bone inflammatory lesions were established on both Stat3 CKO and wild‐type mice, then harvested to assess the bone healing. In response to lipopolysaccharide (LPS) stimulation, osteoblasts from Stat3 CKO and wild‐type mice were subjected to examine the formation of calcium deposits, the expression of osteogenic markers (i.e., Runx2, OPN, COL1A1), and osteoclast‐related markers (i.e., RANKL, OPG). The EdU and transwell assays were performed to assess the proliferation and migration of the cells.ResultsA decrease in bone mass and an increase in osteolysis were found in the inflammatory lesions on Stat3 CKO mice when compared with the control. More osteoclastic‐like cells and an increased expression of RANKL were observed in Stat3 CKO mice. Both mRNA and protein expressions of Stat3 and osteogenic markers in the lesions were significantly decreased in Stat3 CKO mice. After co‐cultured with osteogenic medium, the Stat3‐deficient osteoblasts were found with a significant decrease in calcium deposits and the expression of osteogenic markers, and with a significant increased expression of RANKL. The impaired ossification of Stat3‐deficient osteoblasts was even more pronounced with the presence of lipopolysaccharides in vitro. The most decrease in cell proliferation and migration was found in Stat3‐deficient osteoblasts in response to LPS.ConclusionsLoss of Stat3 in osteoblasts impaired bone healing in an inflammatory microenvironment.

Background Mutations in the signal transducers and activators of transcription 3 (STAT3) gene result in hyper-IgE syndrome(HIES), a rare immunodeficiency that causes abnormalities in immune system, bones and teeth. However, the role of Stat3 in development of dental hard tissues was yet to investigate. Methods In this study, a transgenic mouse of conditional knockout of Stat3 in dental mesenchymal cells (Osx-Cre; Stat3fl/fl, Stat3 CKO) was made. The differences of postnatal tooth development between control and Stat3 CKO mice were compared by histology, µCT and scanning electron microscopy. Result Compared with the control, Stat3 CKO mice were presented with remarkable abnormal tooth phenotypes characterized by short root and thin dentin in molars and incisors. The enamel defects were also found on mandibular incisors. showed that Ki67-positive cells significantly decreased in dental mesenchymal of Stat3 CKO mice. In addition, β-catenin signaling was reduced in Hertwig's epithelial root sheath (HERS) and odontoblasts of Stat3 CKO mice. Conclusions Our results suggested that Stat3 played an important role in dental hard tissues development, and Stat3 may regulate dentin and tooth root development through the β-catenin signaling pathway.