A biomaterial-mediated immune response is a critical factor to determine the cell fate as well as the tissue-regenerative outcome. Although piezoelectric-membranes have attracted considerable interest in the field of guided bone regeneration thanks to their biomimetic electroactivity, the influence of their different surface-charge polarities on the immune-osteogenic microenvironment remains obscure. The present study aimed at investigating the interaction between piezoelectric poly (vinylidene fluoridetrifluoroethylene) [P (VDF-TrFE)] membranes with different surface polarities (negative or positive) and macrophage response, as well as their subsequent influence on osteogenesis from an immunomodulating perspective. Specifically, the morphology, wettability, crystal phase, piezoelectric performance, and surface potential of the synthetic P (VDF-TrFE) samples were systematically characterized. In addition, RAW 264.7 macrophages were seeded onto differently charged P (VDF-TrFE) surfaces, and the culture supernatants were used to supplement cultures of rat bone marrow mesenchymal stem cells (rBMSCs) on the corresponding P (VDF-TrFE) surfaces. Our results revealed that oppositely charged surfaces had different abilities in modulating the macrophage-immune-osteogenic microenvironment. Negatively charged P (VDF-TrFE), characterized by the highest macrophage elongation effect, induced a switch in the phenotype of macrophages from M0 (inactivated) to M2 (anti-inflammatory), thus promoting the osteogenic differentiation of rBMSCs by releasing anti-inflammatory cytokine IL-10. Interestingly, positively charged P (VDF-TrFE) possessed pro-inflammatory properties to induce an M1 (pro-inflammatory) macrophage-dominated reaction, without compromising the subsequent osteogenesis as expected. In conclusion, these findings highlighted the distinct modulatory effect of piezoelectric-P (VDF-TrFE) membranes on the macrophage phenotype, inflammatory reaction, and consequent immune-osteogenic microenvironment depending on their surface-charge polarity. This study provides significant insight into the design of effective immunoregulatory materials for the guided bone regeneration application.

Background Polycystic ovary syndrome (PCOS) is an endocrine-related follicular developmental disorder that affects 50 %-70 % of reproductive-aged women diagnosed with ovulation-related infertility. Abnormal proliferation and apoptosis of granulosa cells (GCs) are thought to be the critical factors leading to abnormal maturation of follicles. It has been shown that microRNAs (miRNAs) exert a significant influence in the pathogenesis of PCOS; however, the relationship between miRNA, PCOS, and GC apoptosis is not entirely understood. Methods To clarify the effect of miR-194 in PCOS, CCK-8, Ki67 staining, AO/EB, and flow cytometry assays were used to assess cell growth, proliferation, and apoptosis in KGN cells, which were artificially stimulated to overexpress miR-194. Luciferase reporter assays and rescue experiments were used to elucidate the mechanism underlying miR-194 in PCOS. Results miR-194 expression was significantly up-regulated in rat models of PCOS and the ovarian GCs of PCOS patients. miR-194 suppression promoted KGN cell growth and proliferation. miR-194 overexpression also induced cell apoptosis, while miR-194 downregulation had an opposite effect. Furthermore, up-regulating heparin-binding EGF-like growth factor (HB-EGF) expression rescued the pro-apoptotic effects of miR-194 upregulation on KGN cells. Conclusions miR-194 is increased in PCOS granulosa cell and may function as a novel biomarker and therapeutic target for KGN cells via HB-EGF regulation.

During bone tissue regeneration, neovascularization is critical, and the formation of a blood supply network is crucial for bone growth stimulation and remodeling. Previous studies suggest that bioelectric signals facilitate the process of angiogenesis. Owing to their biomimetic electroactivity, piezoelectric membranes have garnered substantial interest in the field of guided bone regeneration. Nevertheless, the knowledge of their influence due to varying surface potentials on the progression of angiogenesis remains ambiguous. Therefore, we proposed the preparation of an electroactive material, P(VDF-TrFE), and investigated its effects on the activity and angiogenic functions of human umbilical vein endothelial cells (HUVECs). The HUVECs were directly cultured on P(VDF-TrFE) membranes with different surface potentials. Subsequently, cell viability, proliferation, migration, tube formation, and expressions of related factors were assessed through appropriate assays. Our results revealed that the negative surface potential groups exerted differential effects on the modulation of angiogenesis in vitro. The P(VDF-TrFE) membranes with negative surface potential exhibited the greatest effect on cellular behaviors, including proliferation, migration, tube formation, and promotion of angiogenesis by releasing key factors such as VEGF-A and CD31. Overall, these results indicated that the surface potential of piezoelectric P(VDF-TrFE) membranes could exert differential effects on angiogenesis in vitro. We present a novel approach for designing bioactive materials for guided bone regeneration.

No abstract