Hierarchical Shish-Kebab Structures Functionalizing Nanofibers for Controlled Drug Release and Improved Antithrombogenicity.

The functionalization of the fibrous scaffolds including drug loading and release is of significance in tissue engineering and regenerative medicine. Our previous results have shown that the shish-kebab structure-modified fibrous scaffold shows a completely different microenvironment that mimics the topography of the collagen fibers, which interestingly facilitates the cell adhesion and migration. However, the functionalization of the unique structure needs to be further investigated. In this study, we modified the heparin-loaded fiber with a shish-kebab structure and tuned the kebab structure as the barrier for the sustained release of heparin. The introduction of the kebab structure increases the diffusion energy barrier by extending the diffusion distance. Moreover, the discontinued surface topography of the shish-kebab structure altered the surface chemistry from hydrophobic for the original poly(ε-caprolactone) (PCL) nanofibers to hydrophilic for the PCL nanofibers with the shish-kebab structure, which might have inhibited the activation of fibrinogen and thus improved the anticoagulant ability. This synergistic effect of heparin and the kebab structure significantly promotes the endothelial cell affinity and antithrombogenicity. This method might be a viable and versatile drug delivery strategy in vascular tissue engineering.

Comparison of biological and mechanical properties of different paranasal sinus mucosa in goat.

OBJECTIVE: The present study was designed to explore endurable pressure intensity of different paranasal sinus mucosa in goats. METHOD: Mucosa commonly involved in maxillary sinus augmentation, including mucosa from maxillary sinus crest, maxillary sinus floor, and frontal sinus, were harvested in a computed tomography-guided manner. The obtained mucosa was then sectioned into square and irregular ones for maximum endurable pressure intensity determination and morphological observation, respectively. RESULTS: Thickness of paranasal sinus mucosa, as determined under morphological staining by an optical microscope with a graduated eyepiece, were calculated. And the results showed that the average thickness of maxillary sinus crest mucosa, floor mucosa, and frontal sinus mucosa in goats were 410.03 ± 65.97 µm, 461.33 ± 91.37 µm and 216.90 ± 46.47 µm, respectively. Significant differences between maxillary sinus crest and frontal sinus, maxillary sinus floor, and frontal sinus were observed (P < 0.05). Maximum endurable pressure intensity was determined by utilizing a self-made clamp device and the results revealed maximum endurable pressure intensity of maxillary sinus crest mucosa, floor mucosa and frontal sinus mucosa in goats were 260.08 ± 80.12Kpa, 306.90 ± 94.37Kpa and 121.72 ± 31.72Kpa, respectively. Also, a statistically significant difference was observed when comparing the endurable pressure intensity between maxillary sinus crest and frontal sinus, maxillary sinus floor, and frontal sinus (P < 0.05). Further correlation analysis also revealed a positive correlation between the thickness of mucosa of the maxillary sinus and frontal sinus and maximum endurable pressure intensity (P < 0.05). CONCLUSION: Mucosal thickness and maximum endurable pressure intensity of maxillary sinus crest and floor were larger than that of frontal sinus mucosa and a positive correlation between the thickness of mucosa and endurable pressure intensity was observed. Our results thus might provide an experimental basis and guidance for mucosa-related problems involved maxillary sinus augmentation.

Morphological changes of the root apex in anterior teeth with periapical periodontitis: an in-vivo study.

INTRODUCTION: The aim was to analyze the morphological changes of root apex in anterior teeth with periapical periodontitis. METHODS: 32 untreated anterior teeth with periapical periodontitis were enrolled, compared with the healthy contralateral teeth. Two-dimensional measurement of Cone-beam computed tomography was used to determine the location and measure diameter of the apical constriction according to Schell's methods. An open-source software (3D Slicer) was used to reconstruct the teeth. The apical constriction form was analysis according to Schell's topography. The distances of apical constriction to apical foramen and anatomical apex were measured respectively. RESULTS: The difference value between buccolingual and mesiodistal diameter was (0.06 ± 0.09) mm and (0.04 ± 0.04) mm in periapical periodontitis and controls (p < 0.05). The mean distance between apical constriction and anatomical apex was significantly shorter in periapical periodontitis than controls, so was the mean distance of apical constriction to apical foramen. The most common form of apical constriction was flaring (65.6%) in periapical periodontitis. CONCLUSIONS: The anterior teeth with periapical periodontitis had shorter distances of apical constriction to anatomical apex and apical foramen, bigger disparities between the diameters of buccolingual and mesiodistal, and higher proportion of flaring apical constriction.

Combined Transcriptomic and Metabolomic Analysis Reveals the Role of Phenylpropanoid Biosynthesis Pathway in the Salt Tolerance Process of Sophora alopecuroides.

Salt stress is the main abiotic stress that limits crop yield and agricultural development. Therefore, it is imperative to study the effects of salt stress on plants and the mechanisms through which plants respond to salt stress. In this study, we used transcriptomics and metabolomics to explore the effects of salt stress on Sophora alopecuroides. We found that salt stress incurred significant gene expression and metabolite changes at 0, 4, 24, 48, and 72 h. The integrated transcriptomic and metabolomic analysis revealed that the differentially expressed genes (DEGs) and differential metabolites (DMs) obtained in the phenylpropanoid biosynthesis pathway were significantly correlated under salt stress. Of these, 28 DEGs and seven DMs were involved in lignin synthesis and 23 DEGs and seven DMs were involved in flavonoid synthesis. Under salt stress, the expression of genes and metabolites related to lignin and flavonoid synthesis changed significantly. Lignin and flavonoids may participate in the removal of reactive oxygen species (ROS) in the root tissue of S. alopecuroides and reduced the damage caused under salt stress. Our research provides new ideas and genetic resources to study the mechanism of plant responses to salt stress and further improve the salt tolerance of plants.

Active Transportation of Liposome Enhances Tumor Accumulation, Penetration, and Therapeutic Efficacy.

Liposomes are the first and mostly explored nanocarriers for cancer drug delivery, which have shown great promise in clinical applications, but their limited accumulation and penetration into the tumor interstitial space, significantly reduce the therapeutic efficacy. Here, a γ-glutamyltranspeptidase (GGT)-triggered charge-switchable approach is reported that can trigger the fast endocytosis and transcytosis of the liposome in tumor microenvironments to overcome the harsh biological barriers in tumor tissues. The active transporting liposomal nanocarrier (GCSDL) is prepared by surface modification with a glutathione (GSH) moiety and encapsulated with doxorubicin (DOX). When the GCSDL contacts with tumor vascular endothelial cells, the overexpressed GGT enzyme on cytomembrane catalyzes the hydrolysis of GSH to generate cationic primary amines. The cationic GCSDL triggers fast caveolae-mediated endocytosis and vesicle-mediated transcytosis, resulting in sequential transcytosis to augment its tumor accumulation and penetration. Along with continual intercellular transportation, GCSDL can release DOX throughout the tumor to induce cancer cell apoptosis, resulting in complete eradication of hepatocellular carcinoma and cessation of pancreatic ductal adenocarcinoma's progression. This study develops an efficient strategy to realize high tumor accumulation and deep penetration for the liposomal drug delivery system via active transcytosis.

Interdisciplinary treatment with implant-supported prostheses for an adolescent with ectodermal dysplasia: A clinical report.

This clinical report describes interdisciplinary treatments for a 17-year-old girl with ectodermal dysplasia. The treatment was initiated with orthodontic therapy. After the remaining primary teeth had been extracted, 6 implants were placed in the maxilla with bilateral sinus floor elevations, and 6 implants were placed in the mandible. Immediate restorations were provided. Definitive restorations included screw-retained partial dental prostheses and ceramic crowns.

Development of sandwich ELISAs that can distinguish different types of coxsackievirus A16 viral particles.

Coxsackievirus A16 (CA16) is one of the major causative agents of hand, foot, and mouth disease (HFMD). No CA16 vaccine candidates have progressed to clinical trials so far. Immunogenicity studies indicated that different CA16 particles have much influence on the efficacy of a candidate vaccine. However, there are still no relevant reports on the methods of detecting different CA16 particles. In this study, we screened several monoclonal antibodies (mAbs) specific for different CA16 particles, and several sandwich enzyme-linked immunoassays (ELISAs) were developed to measure the different types of CA16 viral particles. The mAbs that could only bind denatured or empty capsids could not neutralize CA16. In contrast, the mAbs that could bind mature full particles or all types of particles showed obvious neutralizing activity. The thermal stability of different CA16 particles was evaluated using these sandwich ELISAs. The mature full particles were found to be more thermolabile than the other types of particles and could be stabilized by high concentrations of cations. These methods can be used to assist in the potency control of CA16 vaccines and will promote the development of a CA16 vaccine.

Enhanced Germicidal Efficacy by Co-Delivery of Validamycin and Hexaconazole with Methoxy Poly(ethylene glycol)-Poly(lactide-co-glycolide) Nanoparticles.

Co-delivery system has been proposed in pharmaceutical field aim to synergistic treatments. The combination formulation is also important in traditional pesticides formulations based on the low pest resistance risk and wide fungicidal spectrum. However, co-delivery nanoparticles (NPs) tend to be more environmentally friendly for the sustained-release behaviour and none of toxic organic solvents or dusts. Hence, we constructed co-delivery NPs which could delivery two kinds of pesticides, which function was similar with pesticides combination formulation. The co-delivery NPs of validamycin and hexaconazole were prepared with the amphiphilic copolymer methoxy poly(ethylene glycol)- poly(lactide-co-glycolide) (mPEG-PLGA) used an improved double emulsion method. The chemical structure of mPEG-PLGA copolymer was confirmed using fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR). The co-delivery NPs all exhibited good size distribution and held sustained-release property. Germicidal efficacy of the co-delivery NPs against Rhizoctonia cerealis was also studied. The germicidal efficacy of co-delivery NPs against Rhizoctonia cerealis was better than that of traditional pesticides formulation. In addition, co-delivery NPs showed a lasting impact against Rhizoctonia cerealis.

Size-Dependent Effect of Prochloraz-Loaded mPEG-PLGA Micro- and Nanoparticles.

As a controlled release formulation, polymer-based pesticide particle, provide an effective approach to achieve the target crop sites of increasing the pesticide utilization and reducing side effects. The particle size impacts on the dispersibility, pesticide loading content, control effect, etc. It is essential to investigate size-dependent effect. Hence, size-dependent effect of polymer-based pesticide particle was studied systematically in this paper. The biodegradable mPEG-PLGA copolymer with suitable molecular weight (45 KDa) was selected as carrier. Prochloraz-loaded mPEG-PLGA particles with different sizes (190.7 nm, 708.8 nm and 3980.0 nm) were constructed by emulsion/solvent evaporation method based on the same carrier. With the constant mass ratio of copolymer/prochloraz, as the particle size became large, the prochloraz loading content increased, and prochloraz released speed decreased. All prochloraz-loaded particles showed a sustained-release process and sustained impact against the Fusarium graminearum. Among the prochloraz-loaded mPEG-PLGA particles, the 190.7 nm particles exhibited the best germicidal efficacy in two weeks. Hence, the smaller size particles hold a better control efficacy in short time.

Exosomes derived from periodontitis induce hepatic steatosis through the SCD-1/AMPK signaling pathway.

AIM: To investigate the impact of exosomes released by Porphyromonas gingivalis-Lipopolysaccharide activated THP-1 macrophages and human periodontal ligament fibroblasts on hepatocyte fat metabolism. RESULTS: The liver of rats with experimental periodontitis showed obvious steatosis and inflammation compared with control rats. The culture supernatant of macrophages and human periodontal ligament fibroblasts (hPDLFs), when stimulated with Pg-LPS, induced lipogenesis in HepG2 cells. Furthermore, the lipid-promoting effect was effectively inhibited by the addition of the exosome inhibitor GW4869. Subsequently, we isolated exosomes from cells associated with periodontitis. Exosomes released by Pg-LPS-stimulated macrophages and hPDLFs are taken up by hepatocytes, causing mRNA expression related to fat synthesis, promoting triglyceride synthesis, and aggravating NAFLD progression. Finally, two sets of exosomes were injected into mice through the tail vein. In vivo experiments have also demonstrated that periodontitis-associated exosomes promote the development of hepatic injury and steatosis, upregulate SCD-1 expression and inhibit the AMPK signaling pathway. CONCLUSIONS: In conclusion, we found that exosomes associated with periodontitis promote hepatocyte adipogenesis by increasing the expression of SCD-1 and suppressing the AMPK pathway, which indicates that close monitoring of the progression of stomatopathy associated extra-oral disorders is important and establishes a theoretical foundation for the prevention and management of fatty liver disease linked to periodontitis.

Expression and Characterization of Laccase Lac1 from Coriolopsis trogii Strain Mafic-2001 in Pichia pastoris and Its Degradation of Lignin.

The laccase gene (Lac1) was cloned from Coriolopsis trogii strain Mafic-2001. Full-length sequence of Lac1 containing 11 exons and 10 introns is composed of 2140 nucleotides (nts). mRNA of Lac1 encoded for a protein of 517 aa. Nucleotide sequence of the laccase was optimized and expressed in Pichia pastoris X-33. SDS-PAGE analysis showed that the molecular weight of the purified recombinant laccase rLac1 was about 70 kDa. The optimum temperature and pH of rLac1 were 40 ℃ and 3.0, respectively. rLac1 showed high residual activity (90%) in the solutions after 1 h incubation at the pH ranging from 2.5 to 8.0. rLac1 maintained over 60% of laccase activity at the temperatures ranging from 20 to 60 °C, and kept higher than 50% of its activity at 40 °C for 2 h. The activity of rLac1 was promoted by Cu2+ and inhibited by Fe2+. Under optimal conditions, lignin degradation rates of rLac1 on the substrates of rice straw, corn stover, and palm kernel cake were 50.24%, 55.49%, and 24.43% (the lignin contents of substrates untreated with rLac1 were 100%), respectively. Treated with rLac1, the structures of agricultural residues (rice straw, corn stover, and palm kernel cake) were obviously loosened which was reflected by the analysis of scanning electron microscopy and Fourier transform infrared spectroscopy. Based on the specific activity of rLac1 on the degradation of lignin, rLac1 from Coriolopsis trogii strain Mafic-2001 has the potential for in-depth utilization of agricultural residues.

Root canal morphology and bifurcating/merging sites of permanent mandibular incisors in 9- to 12-year-old children: An in-vivo 3D visualization analysis in China.

OBJECTIVE: This retrospective study aims to analyze the root canal morphology of permanent mandibular incisors and the bifurcating/merging sites of root canal systems in children aged 9-12 in a Chinese subpopulation.Design Cone-beam computed tomography scans of 976 healthy, untreated and fully developed mandibular incisors were collected. Root canal morphology was identified by Vertucci's classification. Combined three-dimensional reconstruction and visualization techniques were used to locate bifurcating/merging sites in root canals. RESULTS: Vertucci I was the most common classification of mandibular central incisors (42.3%) while Vertucci III was most common in mandibular lateral incisors (37.9%). Females more frequently showed Vertucci I classification (49.5% central incisors and 36.7% lateral incisors) while Vertucci III was most common among males (44.5% central incisors and 41.0% lateral incisors). The difference in canal classification by sex was statistically significant (p < 0.05). 58.7% of Vertucci V canals bifurcated in the apical third (AT) in central incisors, while 69.5% bifurcated in the middle third (MT) in lateral incisors. Bifurcating and merging in AT (44.3%) was the most common style of Vertucci III canals in central incisors, while bifurcating in MT and merging in AT (53.8%) was the most common in lateral incisors. CONCLUSION: The root canal morphology of mandibular incisors in children aged 9-12 was different from that reported in previous studies on adults, and closely related to sex. Males had significantly greater canal variability than females. Lateral incisors had greater canal variability than central incisors. The bifurcating/merging sites were closely related to tooth type.

Elevated pCO2 alleviates the toxic effects of polystyrene nanoparticles on the marine microalga Nannochloropsis oceanica.

Concerns about the environmental effects of nanoplastics on marine ecosystems are increasing. Ocean acidification (OA) has also become a global environmental problem. Plastic pollution occurs concomitantly with anthropogenic climate stressors such as OA. However, the combined effects of NP and OA on marine phytoplankton are still not well understood. Therefore, we have investigated the behavior of ammonia (NH2) polystyrene nanoparticles (PS NP) in f/2 medium under 1000 µatm pCO2 and discussed the toxicity of PS NP (100 nm; 0.5 and 1.5 mg/L) on Nannochloropsis oceanica under long and short-term acidification (LA and SA; pCO2 ~ 1000 µatm). We observed PS NP suspended in pCO2 1000 µatm f/2 medium aggregated to a size greater than nanoscale (1339.00 ± 76.10 nm). In addition, we found that PS NP significantly inhibited the growth of N. oceanica at two concentrations, which also produced oxidative stress. Whereas, the growth of algal cells under the coupling of acidification and PS NP was significantly better than that of single PS NP exposure. This indicated that acidification significantly alleviated the toxic effects of PS NP on N. oceanica, and long-term acidification can even promote the growth of N. oceanica under low-density NP. To further understand the mechanism, we analyzed a comparative transcriptome. The results showed that PS NP exposure inhibited the expression of genes involved in the TCA cycle. The acidification was possibly reflected in ribosomes and corresponding processes, which alleviated the negative effects of PS NP on N. oceanica by promoting the synthesis of related enzymes and proteins. This study provided a theoretical basis for assessing the damage of NP to marine phytoplankton under OA. We propose that future studies evaluating the toxicology of NP to marine ecology should consider the changing ocean climate.

Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies.

Diabetes is one of the most socially challenging health concerns. Even though islet transplantation has shown promise for insulin-dependent diabetes, there is still no effective method for curing diabetes due to the severe shortage of transplantable donors. In recent years, organoid technology has attracted lots of attention as organoid can mirror the human organ in vivo to the maximum extent in vitro, thus bridging the gap between cellular- and tissue/organ-level biological models. Concurrently, human pancreatic islet organoids are expected to be a considerable source of islet transplantation. To construct human islet-like organoids, the seeding cells, biomaterials and three-dimensional structure are three key elements. Herein, this review summarizes current progresses about the cell origins, biomaterials and advanced technology being applied to make human islet organoids, and discusses the advantages, shortcomings, and future challenges of them as well. We hope this review can offer a cross-disciplinary perspective to build human islet organoids and provide insights for tissue engineering and regenerative medicine.

Ligature induced periodontitis in rats causes gut dysbiosis leading to hepatic injury through SCD1/AMPK signalling pathway.

AIMS: Previous studies have demonstrated that chronic periodontitis (CP) is closely associated with the occurrence and development of a variety of systemic diseases. In this study, we successfully constructed a rat CP model through dental silk ligation, and the corresponding inflammatory reactions and fatty lesions were observed in the liver. MAIN METHODS: Sprague-Dawley rats (n = 6) underwent tooth ligation at the bilateral first molars with silk thread to induce CP and were sacrificed 8 weeks later and compared to non-ligated rats (n = 6). RNA sequencing and 16S rRNA analysis were performed to determine the molecular mechanisms of CP involved in inducing liver disease. Alveolar bone loss, liver enzymes, mandible and liver histopathology, and inflammatory responses were compared between groups. KEY FINDINGS: RNA sequencing of liver tissue showed that the expression of SCD1 increased significantly in CP rats compared to controls. KEGG enrichment analysis showed that the AMPK signalling pathway may be involved in liver steatosis. The intestinal flora of faecal samples of rats were analysed by 16S rRNA sequencing, and the results indicated that the intestinal flora of the CP group was evidently imbalanced. The expression levels of tight junction proteins (ZO-1, occludin, and claudin-1) were significantly reduced in CP rats. Meanwhile, increases in serum IL-1ß and lipopolysaccharide in CP rats reflected a systemic inflammatory response. SIGNIFICANCE: CP may be involved in the occurrence and development of hepatic injury and liver steatosis, and its mechanism may be related to the oral-gut-liver axis and SCD1/AMPK signal activation in the liver.

Ultrasound-Activatable Phase-Shift Nanoparticle as a Targeting Antibacterial Agent for Efficient Eradication of Pseudomonas aeruginosa Biofilms.

Biofilms are physical barriers composed of extracellular polymeric substances (EPS) that enable planktonic bacteria to resist host responses and antibacterial treatments, complicating efforts to clear bacteria such as Pseudomonas aeruginosa (P. aeruginosa) and thereby contributing to persistently chronic infections. As such, it is critical to develop a robust antimicrobial strategy capable of effectively eradicating P. aeruginosa biofilms and to further address aggressive clinical infection. In this study, ultrasound-activatable targeted nanoparticles were designed by using poly(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate phase-transformable perfluoropentane (PFP) and the antibiotic meropenem via a double emulsion approach, followed by conjugation with anti-P. aeruginosa antibodies. In this strategy, ultrasound exposure can trigger PFP to produce microbubbles, inducing ultrasonic cavitation effects that can disrupt EPS components and allow nanoparticles to release meropenem to kill P. aeruginosa directly and accelerate the associated wound healing. These nanoparticles eradicated biofilms effectively and cleared bacteria in vitro as well as exhibited potent anti-infective activity in vivo. In summary, this study demonstrates the efficacy of a sonobactericidal strategy as a means of effectively and reliably eliminating biofilms.

Covalent immobilization of the phytic acid-magnesium layer on titanium improves the osteogenic and antibacterial properties.

In order to improve early osseointegration and long-term survival rate of implants, a multifunctional titanium surface that promotes osteogenesis and antibacterial properties is expected. Incorporation of bioactive trace elements such as magnesium ions was proved a promising method to improve osseointegration of titanium. Phytic acid has strong chelating ability with multivalent cations, which has been used in surface modification. Moreover, phytic acid was proved antibacterial potential. Herein, to improve the osteogenic and antibacterial properties, a phytic acid-magnesium (PA-Mg) layer was introduced on titanium using phytic acid as a cross-linker molecule. No obvious changes of the surface characterization were observed by scanning electron microscopy and atomic force microscopy. X-ray photoelectron spectroscopy confirmed that the PA-Mg layer covalently bond to the Ti surface, and the thickness of the PA-Mg layer was about 150 nm. Besides, improved hydrophilic and more protein adsorption were observed on Ti-PA-Mg. Notably, a relatively controlled magnesium release was also observed on Ti-PA-Mg. Human bone mesenchymal stem cells showed better adhesion, proliferation, and osteogenic differentiation on Ti-PA-Mg samples, indicating improved biocompatibility and osteoinductivity. Moreover, Ti-PA-Mg had better antibacterial properties against porphyromonas gingivalis than Ti. Overall, the PA-Mg layer on Ti surface improved the osteogenic and antibacterial properties, which may have promise for use in dental implantation.

Targeting TSP-1 decreased periodontitis by attenuating extracellular matrix degradation and alveolar bone destruction.

An important factor in periodontitis pathogenesis relates to a network of interactions of various cytokines. Thrombospondin-1 (TSP-1) is upregulated in several inflammatory diseases. We previously found that Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS)-induced TSP-1 production, and that TSP-1 simultaneously and effectively elevated inflammatory cytokines in THP-1 macrophages. This suggests that TSP-1 plays an important role in the pathology of periodontitis. However, the function of TSP-1 on oral cells is largely unknown. This study aimed to elucidate the underlying molecular mechanisms of TSP-1 in human periodontal fibroblasts (hPDLFs). We demonstrated that TSP-1 is highly expressed in the gingival crevicular fluid of patients with chronic periodontitis and in the inflammatory gingival tissues of rats. TSP-1 overexpression or treatment with recombinant human TSP-1(rTSP-1) promoted the expression of MMP-2, MMP-9 and RANKL/OPG in hPDLFs, while anti-TSP-1 inhibited cytokines production from P. gingivalis LPS-treated hPDLFs. Additional experiments showed that SB203580 (a special p38MAPK inhibitor) inhibited MMP-2, MMP-9 and RANKL/OPG expression induced by rTSP-1. Thus, TSP-1 effectively promoted P. gingivalis LPS-induced periodontal tissue (extracellular matrix (ECM) and alveolar bone) destruction by the p38MAPK signalling pathway, indicating that it may be a potential therapeutic target against periodontitis.

Endothelial Cell Migration Regulated by Surface Topography of Poly(ε-caprolactone) Nanofibers.

The study of cell migration on biomaterials is of great significance in tissue engineering and regenerative medicine. In recent years, there has been increasing evidence that the physical properties of the extracellular matrix (ECM), such as surface topography, affect various cellular behaviors such as proliferation, adhesion, and migration. However, the biological mechanism of surface topography influencing cellular behavior is still unclear. In this study, we prepared polycaprolactone (PCL) fibrous materials with different surface microstructures by solvent casting, electrospinning, and self-induced crystallization. The corresponding topographical structure obtained is a two-dimensional (2D) flat surface, 2.5-dimensional (2.5D) fibers, and three-dimensional (3D) fibers with a multilevel microstructure. We then investigated the effects of the complex topographical structure on endothelial cell migration. Our study demonstrates that cells can sense the changes of micro- and nanomorphology on the surface of materials, adapt to the physical environment through biochemical reactions, and regulate actin polymerization and directional migration through Rac1 and Cdc42. The cells on the nanofibers are elongated spindles, and the positive feedback of cell adhesion and actin polymerization along the fiber direction makes the plasma membrane continue to protrude, promoting cell polarization and directional migration. This study might provide new insights into the biomaterial design, especially those used for artificial vascular grafts.

Periostin reverses high glucose-inhibited osteogenesis of periodontal ligament stem cells via AKT pathway.

AIMS: Diabetes mellitus leads to impaired osteogenic differentiation and alveolar bone absorption. Periostin (POSTN) is important for bone and tooth maintenance. This study aims to elucidate the expression of POSTN in high glucose and the effects of both high glucose and POSTN on osteogenesis in hPDLSCs, as well as the underlying mechanism. MAIN METHODS: Cells were incubated with glucose under physiological (5.5 mM normal glucose) or diabetic (30 mM high glucose) conditions in the presence or absence of recombinant human POSTN (rPOSTN). Cell migration was assessed by a scratch assay. Reactive oxygen species (ROS) was used to assess HG-induced oxidative damage. Osteogenesis was evaluated by alkaline phosphatase (ALP) activity and ALP staining, Alizarin Red staining (ARS), as well osteogenic related genes and proteins. KEY FINDINGS: POSTN expression was inhibited during a long-term culture with HG. HG diminished the migration and osteogenesis of hPDLSCs as indicated by decreases in ALP activity and ALP staining, ARS and expression of COL I, RUNX2, OSX, OPN and OCN, but an increase in reactive oxygen species overproduction. All of which were reversed by addition of rPOSTN. POSTN knockdown suppressed migration and osteogenesis of hPDLSCs. Moreover, HG inhibited activation of AKT, which was rescued by addition of POSTN. AKT inhibitor significantly reduced POSTN-mediated osteogenic differentiation. SIGNIFICANCE: rPOSTN could be a therapeutic regime for defective periodontal and peri-implant bone regeneration in diabetes mellitus.