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(1) Background: Vascularization remains a critical challenge in bone tissue engineering. The objective of this study was to prevascularize calcium phosphate cement (CPC) scaffold by co-culturing human periodontal ligament stem cells (hPDLSCs) and human umbilical vein endothelial cells (hUVECs) for the first time, (2) Methods: hPDLSCs and/or hUVECs were seeded on CPC scaffolds. Three groups were tested: (i) hUVEC group (hUVECs on CPC), (ii) hPDLSC group (hPDLSCs on CPC), (iii) co-culture group (hPDLSCs + hUVECs on CPC). Osteogenic differentiation, bone mineral synthesis, and microcapillary-like structures were evaluated, (3) Results: Angiogenic gene expressions of co-culture group were 6–9 fold those of monoculture. vWF expression of co-culture group was 3 times lower than hUVEC-monoculture group. Osteogenic expressions of co-culture group were 2–3 folds those of the hPDLSC-monoculture group. ALP activity and bone mineral synthesis of co-culture were much higher than hPDLSC-monoculture group. Co-culture group formed capillary-like structures at 14–21 days. Vessel length and junction numbers increased with time, (4) Conclusions: The hUVECs + hPDLSCs co-culture on CPC scaffold achieved excellent osteogenic and angiogenic capability in vitro for the first time, generating prevascularized networks. The hPDLSCs + hUVECs co-culture had much better osteogenesis and angiogenesis than monoculture. CPC scaffolds prevacularized via hPDLSCs + hUVECs are promising for dental, craniofacial, and orthopedic applications.

The objective of this study was to develop a novel nanostructured resin infiltrant containing nanoparticles of amorphous calcium phosphate (NACP) to treat enamel white spot lesions (WSLs). Physical properties and the therapeutic effect of the new resin infiltrant were investigated for the first time.NACP was incorporated into ICON (Icon caries infiltrant, DMG, Germany) with different mass fractions. Cytotoxicity, degree of conversion, surface hardness, calcium (Ca) and phosphorus (P) ions release concentrations were tested. After application to the demineralized enamel samples, the color changes were determined. Surface and cross-sectional hardness were measured, scanning electron microscopy (SEM) images were taken on the cross-section of samples to observe microstructure changes after 14-day pH cycling.Incorporating 10%-30% of NACP did not compromise the biocompatibility and physical properties of the resin infiltrant. ICON + 30% NACP group had long-lasting and high level of Ca and P ion release. After 14-day pH cycling, enamel surface hardness of ICON + 30% NACP group was 1.83 ± 0.21 GPa, significantly higher than the control group (1.32 ± 0.18 GPa) (p 0.05). ICON + 30NACP group had the highest cross-sectional enamel hardness among all groups (p 0.05), especially at 50 μm and 100 μm depth. SEM images showed that apparent enamel prism and inter-prism gaps in negative control were masked by mineral deposition in ICON + 30% NACP group.The novel ICON+30% NACP infiltrant is promising to inhibit enamel WSLs, protect the enamel and increase its hardness.

Bone tissue engineering is a promising approach that uses seed-cell-scaffold drug delivery systems to reconstruct bone defects caused by trauma, tumors, or other diseases (e.g., periodontitis). Metformin, a widely used medication for type II diabetes, has the ability to enhance osteogenesis and angiogenesis by promoting cell migration and differentiation. Metformin promotes osteogenic differentiation, mineralization, and bone defect regeneration via activation of the AMP-activated kinase (AMPK) signaling pathway. Bone tissue engineering depends highly on vascular networks for adequate oxygen and nutrition supply. Metformin also enhances vascular differentiation via the AMPK/mechanistic target of the rapamycin kinase (mTOR)/NLR family pyrin domain containing the 3 (NLRP3) inflammasome signaling axis. This is the first review article on the effects of metformin on stem cells and bone tissue engineering. In this paper, we review the cutting-edge research on the effects of metformin on bone tissue engineering. This includes metformin delivery via tissue engineering scaffolds, metformin-induced enhancement of various types of stem cells, and metformin-induced promotion of osteogenesis, angiogenesis, and its regulatory pathways. In addition, the dental, craniofacial, and orthopedic applications of metformin in bone repair and regeneration are also discussed.

500kV autotransformer has split type and integrated type. The current transformer (CT) position of low voltage side is different for these two types of autotransformer. This paper analyzes circulating current in autotransformer’s delta winding when single-phase grounding fault takes place on high voltage side. Protection setting method considering circulating current in delta winding is proposed for split type autotransformer. Simulation results verify the position of two types of autotransformer’s CT influences the circulation current in low voltage side protection. Protection setting for an autotransformer used in Shandong electric power grid tests the correctness of the over-current protection setting with circulating current proposed in this paper.

Objectives This study aimed to investigate the biological roles and mechanisms of compressive force-stimulated periodontal ligament fibroblasts (PDLFs) on polarization of macrophages Design PDLFs were stimulated with or without static compressive force, and then conditioned medium, high-molecular weight proteins and low-molecular weight proteins were collected to treat THP-1 macrophages. RT-qPCR and flow cytometric analysis were used to evaluate the polarization of macrophages. Exosomes were isolated by ultracentrifugation method and identified via transmission electron microscopy, western-blot and nano-tracking analysis. The protein level of Yes-Associated Protein (YAP) contained in exosomes was detected by western blot. GW4869 and Verteporfin were used to inhibit exosome secretion and YAP- TEA domain transcription factor (TEAD) interaction respectively. Results Exosomes were successfully purified from PDLFs and could be efficiently incorporated into THP-1 macrophages. conditioned medium, HMW proteins and exosomes derived from compressive force-treated PDLFs significantly induce M1 polarization of macrophages. While inhibiting exosomes secretion by GW4869 treatment eliminated the inductive effect. YAP target genes, connective tissue growth factor (CTGF) and cysteine-rich angiogenic inducer 61 (CYR61) were upregulated in macrophages when treated with exosomes derived from compressive force-treated PDLFs (F-Exo). YAP level was elevated in the F-Exo. When macrophages were treated with Verteporfin, expression of YAP target genes and M1 polarization were significantly downregulated. Conclusion These results suggested that exosomes derived from compressive force-treated PDLFs promoted the M1 polarization of the THP-1 macrophages. The elevated level of YAP in the exosomes may be a critical factor for this response.

Human periodontal ligament stem cells (hPDLSCs) are promising for tissue engineering applications but have received relatively little attention. Human platelet lysate (HPL) contains a cocktail of growth factors. To date, there has been no report on hPDLSC seeding on scaffolds loaded with HPL. The objectives of this study were to develop a calcium phosphate cement (CPC)–chitosan scaffold loaded with HPL and investigate their effects on hPDLSC viability, osteogenic differentiation and bone mineral synthesis for the first time. hPDLSCs were harvested from extracted human teeth. Scaffolds were formed by mixing CPC powder with a chitosan solution containing HPL. Four groups were tested: CPC–chitosan + 0% HPL (control); CPC–chitosan + 2.66% HPL; CPC–chitosan + 5.31% HPL; CPC–chitosan + 10.63% HPL. Scanning electron microscopy, live/dead staining, CCK-8, qRT-PCR, alkaline phosphatase and bone minerals assay were applied for hPDLSCs on scaffolds. hPDLSCs attached well on CPC–chitosan scaffold. Adding 10.63% HPL into CPC increased cell proliferation and viability (p < 0.05). ALP gene expression of CPC–chitosan + 10.63% HPL was 7-fold that of 0% HPL at 14 days. Runx2, OSX and Coll1 of CPC–chitosan + 10.63% HPL was 2–3 folds those at 0% HPL (p < 0.05). ALP activity of CPC–chitosan + 10.63% HPL was 2-fold that at 0% HPL (p < 0.05). Bone minerals synthesized by hPDLSCs for CPC–chitosan + 10.63% HPL was 3-fold that at 0% HPL (p < 0.05). This study showed that CPC–chitosan scaffold was a promising carrier for HPL delivery, and HPL in CPC exerted excellent promoting effects on hPDLSCs for bone tissue engineering for the first time. The novel hPDLSC–CPC–chitosan–HPL construct has great potential for orthopedic, dental and maxillofacial regenerative applications.

Objective Human periodontal ligament stem cells (hPDLSCs) are promising for periodontal regeneration. However, to date, there has been no report of hPDLSC differentiation into the fibrogenic lineage. There has been no report demonstrating hPDLSC differentiation into all three (osteogenic, fibrogenic and cementogenic fibrogenic) lineages in the same report. The objectives of this study were to harvest hPDLSCs from the periodontal ligaments (PDL) of the extracted human teeth, and use the same vial of hPDLSCs to differentiate into all three (osteogenic, fibrogenic and cementogenic) lineages for the first time. Methods hPDLSCs were harvested from PDL tissues of the extracted premolars. The ability of hPDLSCs to form bone, cementum and collagen fibers was tested in culture mediums. Gene expressions were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Immunofluorescence, alizarin red (ARS), Xylenol orange, picro sirius red staining (PSRS), alcian blue staining (ABS) and alkaline phosphatase (ALP) staining were evaluated. Results In osteogenic medium, hPDLSCs had high expressions of osteogenic genes (RUNX2, ALP, OPN and COL1) at 14 and 21 days (15–20 folds of that of control), and produced mineral nodules and ALP activity (5 and 10 folds those of the control). hPDLSCs in fibrogenic medium expressed high levels of PDL fibrogenic genes (COL1, COL3, FSP-1, PLAP-1 and Elastin) at 28 days (20–70 folds of control). They were stained strongly with F-actin and fibronection, and secreted PDL collagen fibers (5 folds of control). hPDLSCs in cementogenic medium showed high expressions of cementum genes (CAP, CEMP1 and BSP) at 21 days (10–15 folds of control) and synthesized mineralized cementum (50 folds via ABS, and 40 folds via ALP staining, compared to those of control). Conclusions hPDLSCs differentiated into bone-, fiber- and cementum-forming cells, with potential for regeneration of periodontium to form the bone-PDL-cementum complex.

Dental caries is prevalent worldwide. Tooth cavity restorations cost more than $46 billion annually in the United States alone. The current generation of esthetic polymeric restorations have unsatisfactory failure rates. Replacing the failed restorations accounts for 50–70% of all the restorations. This article reviewed developments in producing a new generation of bioactive and therapeutic restorations. This includes: Protein-repellent and anti-caries polymeric dental composites, especially the use of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminododecyl methacrylate (DMAHDM); protein-repellent adhesives to greatly reduce biofilm acids; bioactive cements to inhibit tooth lesions; combining protein-repellency with antibacterial nanoparticles of silver; tooth surface coatings containing calcium phosphate nanoparticles for remineralization; therapeutic restorations to suppress periodontal pathogens; and long-term durability of bioactive and therapeutic dental polymers. MPC was chosen due to its strong ability to repel proteins. DMAHDM was selected because it had the most potent antibacterial activity when compared to a series of antibacterial monomers. The new generation of materials possessed potent antibacterial functions against cariogenic and periodontal pathogens, and reduced biofilm colony-forming units by up to 4 logs, provided calcium phosphate ions for remineralization and strengthening of tooth structures, and raised biofilm pH from a cariogenic pH 4.5 to a safe pH 6.5. The new materials achieved a long-term durability that was significantly beyond current commercial control materials. This new generation of bioactive and nanostructured polymers is promising for wide applications to provide therapeutic healing effects and greater longevity for dental restorations.

Objectives (1) develop a CPC-metformin scaffold with hPDLSC seeding for bone tissue engineering; and (2) investigate the effects of CPC-metformin scaffold on hPDLSC proliferation, osteogenic differentiation and bone matrix mineralization for the first time. Methods hPDLSCs were harvested from extracted teeth. CPC scaffolds (with or without metformin) were prepared. Three groups were tested: (1) control group (growth medium); (2) osteogenic group (osteogenic medium); (3) metformin + osteogenic group (CPC-metformin scaffold, cultured in osteogenic medium). hPDLSC viability, osteogenic differentiation and mineralization were measured. SEM was used to examine cell morphology. Results After culturing for 14 days, all three groups demonstrated excellent hPDLSC attachment and viability, as shown in live-dead staining, CCK-8 assay, and SEM examinations. The osteogenic group had 3–8 folds, 5 folds and 6 folds of increases in osteogenic gene expressions, ALP activity and mineral synthesis, compared to control group. Furthermore, the metformin + osteogenic group had 3-fold to 4-fold increases over those of the osteogenic group in osteogenic gene expressions, ALP activity and mineral synthesis. Conclusions hPDLSCs were demonstrated to be a potent cell source for bone engineering. The novel CPC-metformin-hPDLSC construct is highly promising to enhance bone repair and regeneration efficacy in dental, craniofacial and orthopedic applications.

A method to improve the durability of electrically conductive polyacrylonitrile (PAN) fibers treated with the CuxS method was developed in this article. The influence of pretreatment with activators and posttreatment with polysulfide on the durability was studied, and the mechanism was proposed. The results showed that, combining activation with acetic acid with posttreatment with polysulfide, the durability of the electrically conductive fiber increased. This is attributed to the swelling and etching effects of the activator as well as the formation of uniform, thick, and compact conductive layers obtained from polysulfide treatment. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 1039–1045, 1999