Physiological Microenvironment Dependent Self-Cross-Linking of Multifunctional Nanohybrid for Prolonged Antibacterial Therapy via Synergistic Chemodynamic-Photothermal-Biological Processes.

Herein, a multifunctional nanohybrid (PL@HPFTM nanoparticles) was fabricated to perform the integration of chemodynamic therapy, photothermal therapy, and biological therapy over the long term at a designed location for continuous antibacterial applications. The PL@HPFTM nanoparticles consisted of a polydopamine/hemoglobin/Fe2+ nanocomplex with comodification of tetrazole/alkene groups on the surface as well as coloading of antimicrobial peptides and luminol in the core. During therapy, the PL@HPFTM nanoparticles would selectively cross-link to surrounding bacteria via tetrazole/alkene cycloaddition under chemiluminescence produced by the reaction between luminol and overexpressed H2O2 at the infected area. The resulting PL@HPFTM network not only significantly damaged bacteria by Fe2+-catalyzed ROS production, effective photothermal conversion, and sustained release of antimicrobial peptides but dramatically enhanced the retention time of these therapeutic agents for prolonged antibacterial therapy. Both in vitro and in vivo results have shown that our PL@HPFTM nanoparticles have much higher bactericidal efficiency and remarkably longer periods of validity than free antibacterial nanoparticles.

[Preparation and Tumor Targeting Analysis of Cell Membrane Nanovesicles Derived from Breast Cancer Cells].

Objective: To prepare cell membrane nanovesicles (NVs) derived from breast cancer cells, to explore their basic characteristics, tumor cell endocytosis, and in vivo distribution in a tumor-bearing mouse model, and to investigate their tumor targeting properties. Methods: 4T1 breast cancer cells were cultured in vitro. The cell membrane of 4T1 cells was isolated through ultracentrifugation and NVs were formulated with a liposome extruder. The size distribution of NVs was determined by way of dynamic light scattering, and the morphology properties of the NVs were examined with transmission electron microscope. The stability of NVs was analyzed by measuring the diameter changes of NVs submerged in phosphate-buffered saline (PBS). The biocompatibility of NVs was investigated by measuring the viability of dendritic cells treated with NVs at different concentrations (5, 10, 20, 50, and 100 mg·L -1) by CCK-8 assay. Fluorescence microscopy was used to analyze the cellular uptake of NVs by breast cancer cells. A mice model of breast cancer model was established with mice bearing subcutaneous xenograft of 4T1 cells. The mice were treated with Cy5.5-labeled NVs injected via the tail vein and the in vivo distribution of NVs was analyzed with an imaging system for small live animals. Results: The results showed that NVs derived from 4T1 breast cancer cells were successfully prepared. The NVs had a mean diameter of 123.2 nm and exhibited a hollow spherical structure under transmission electron microscope. No obvious change in the size of the NVs was observed after 7 days of incubation in PBS solution. CCK-8 assay results showed that the viability of dendritic cells treated with NVs at different concentrations was always higher than 90%. Fluorescence microscopic imaging showed that NVs could be efficiently internalized into breast cancer cells. in vivo biodistribution analysis revealed that breast cancer cell-derived NVs showed higher distribution in tumor tissue than the NVs prepared with normal cells did. Conclusion: We successfully prepared cell membrane NVs derived from 4T1 breast cancer cells. These NVs had efficient cellular uptake by breast cancer cells and sound tumor targeting properties.

Effects of type 2 diabetes and metformin on salivary microbiota in patients with chronic periodontitis.

Diabetes is closely associated with periodontitis, however, the effects of type 2 diabetes and metformin treatment on the salivary microbiota in chronic periodontitis patients are still insufficiently studied. Saliva was collected from ten patients with moderate to severe chronic periodontitis (CP group) and 20 patients with type 2 diabetes mellitus (T2DM) and moderate to severe chronic periodontitis (ten patients were newly diagnosed with diabetes without drug treatment (DM group), and ten patients were treated with metformin (CP-DM-MET group)). Total DNA was extracted. DNA amplicons of the V3-V4 hypervariable regions of the 16S rRNA gene were generated and subjected to high-throughput sequencing. There was no significant difference in the alpha diversity of the salivary microbiota (Observed_Species, Shannon, Simpson, ACE, Chao1 index) among the three groups. The dominant phyla with relative abundances greater than 1% were Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, Fusobacteriota, and Spirochaetota, and no significant difference was found among the three groups. Compared with the CP group, the relative abundance of twelve genera was found changed in CP-DM group, for example, Aggregatibacter, Unclassified_f_Neisseriaceae, Parvimonas, Erysipelotrichace_UCG-006, Atopobium, and Endomicrobium et al. Metformin treatment could partly restore the abundance of several genera in CP-DM, such as Acholeplasma and Comamonas. Compared with the CP group, genus Lactobacillus, Parvimonas, Norank_f_norank_o_Absconditabacteriales_SR1, and Acholeplasma changed significantly in CP-DM-MET group. Plaque index (PLI) was positively correlated with Prevotella and Lactobacillus but negatively correlated with Haemophilus, Lautropia, Unclassified_f_Pasteurellaceae, and TM7x. In conclusion, there was a significant difference in the salivary microbiota of patients with chronic periodontitis complicated by T2DM. Treatment with metformin partially alleviated the alteration in salivary microbiota caused by T2DM.

Digitally predesigned positioning tray and custom restoration shell for immediate implantation prothesis: a digital workflow.

The present article introduces a new digital workflow for the fabrication of an immediate implantation prothesis. With this technique, based on the surgical planning, the positioning tray and the restoration shell are predesigned and premanufactured together with the implant guide before the physical surgery. After implantation, the restoration shell is placed and bonded with a temporary abutment guided by the positioning tray, which acts as a type of tooth-borne device to guide the placement and bonding of the immediate restoration. The restoration shell acts as a type of hollowed out restoration in the tissue surface to improve the implantation error tolerance.

Strengthening Gastric Cancer Therapy by Trastuzumab-Conjugated Nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine.

BACKGROUND/AIMS: MicroRNA-21 is an oncogenic miR (oncomiR) frequently elevated in gastric cancer (GC). Overexpression of miR-21 decreases the sensitivity of GC cells to 5-fluorouridine (5-Fu) and trastuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including anti-miRNA oligonucleotides (AMOs). This study is a continuation of earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target GC with HER2 receptor over-expression using anti-miRNA-21 (AMO-21) and 5-Fu. METHODS: HER-PEG-PCL NPs were prepared by one-step carbodiimide coupling using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAc) and Sulfo-NHS in aqueous phase. Covalent coupling of amino groups at the surface of PEG-PCL with the carboxyl groups of trastuzumab was analyzed by X-ray photoelectron spectroscopy (XPS). AMO-21/5-Fu NPs were formulated by a double-emulsion solvent evaporation technique. The cell line specificity, cellular uptake and AMO-21 delivery were investigated through the rhodamine-B-labeled 6-carboxyfluorescein (FAM)-AMO-21-PEG-PCL NPs coated with or without the antibody in both Her2-positive (NUGC4) and negative GC cells (SGC7901) visualized by fluorescence microscopy. The cytotoxicity of the HER-PEG-PCL NPs encapsulating AMO-21 was evaluated by MTT and apoptosis. Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to examine miR-21 and phosphatase and tensin homolog (PTEN) and Sprouty2 expression in GC cell lines. The antitumor effects of AMO-21/5-Fu NPs were compared with other groups in xenograft gastric cancer mice. RESULTS: The antibody conjugates significantly enhanced the cellular uptake of NPs. The AMO-21/5-Fu NPs effectively suppressed the target miRNA expression in GC cells, which further up-regulated PTEN and Sprouty2. As a result, the sensitivity of HER2-expressing gastric cancer to trastuzumab and 5-Fu were enhanced both in vitro and in vivo. The approach enhanced the targeting by trastuzumab as well as antibody-dependent cellular cytotoxicity (ADCC) of immune effector cells Conclusions: Taken together, the results provide insight into the biological and clinical potential of targeted AMO-21 and 5-Fu co-delivery using modified trastuzumab for GC treatment.

Risk factor analysis of refracture in the same cemented vertebra after percutaneous kyphoplasty for Kümmell's disease.

OBJECTIVE: The objective of this study was to evaluate the factors that affect refracture in the same cemented vertebra after percutaneous kyphoplasty (PKP) for Kümmell's disease (KD) and establish a risk prediction score. METHODS: A total of 2932 patients who were treated with PKP for KD between January 2019 and December 2021 were retrospectively reviewed. After inclusion and exclusion criteria were applied, 191 patients were included in the study. According to the criteria for refracture, there were 50 patients in the refracture group and 141 patients in the no-refracture group. Twenty-five factors were analyzed. Patient demographics, medical history, imaging data, surgical data, and postoperative management were reviewed. Multivariate logistic regression modeling was used to identify the independent risk factors for refracture. Receiver operating characteristic (ROC) curve analysis was used to assess and establish a risk score system and further predict the risk of refracture. RESULTS: In this study, 50 (26.2%) patients developed a refracture. Through univariate analysis, bone mineral density (BMD) (p < 0.001), compression rate (p = 0.007), classification (i.e., the stages determined by the compression ratios) (p < 0.001), bone cement volume (p < 0.001), volume fraction (p < 0.001), distribution pattern (p = 0.007), non-PMMA endplate contact (p < 0.001), and anti-osteoporosis therapy (p < 0.001) were found to be significant factors for post-cement vertebral refracture after PKP in patients with KD. Three independent risk factors were found to be significant for refracture: small volume fraction, low BMD, and no anti-osteoporosis therapy. One point was assigned for each factor. The incidence rates of refracture in patients with scores of 0, 1, 2, and 3 were 3.7%, 4.4%, 42.0%, and 100%, respectively. The area under the ROC curve for this risk prediction score was 0.888 (p < 0.001), indicating moderate accuracy. CONCLUSIONS: Volume fraction, BMD, and osteoporosis therapy are the main factors influencing the refracture of the same cemented vertebra in KD. On the basis of these factors, the risk prediction score developed in this paper can be used to forecast the incidence of refracture.

Periapical lesion-derived decellularized extracellular matrix as a potential solution for regenerative endodontics.

Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM's in situ transplantation for regenerative endodontics.

Clinical decision making of implant guidance methods guided by new classification of surgical area mouth ope-ning.

When selecting implant guidance methods or judging whether the patient can be implanted, many doctors ignore or only use visual inspection to estimate a patient's mouth opening. This phenomenon often leads to failure to complete the implantation due to insufficient mouth opening or the deflection of the implant due to limited angle, resulting in the high incidence of corresponding complications. The main reason is that doctors lack accurate analysis and control of the overall geometric conditions of the intraoral surgical area, and three-dimensional position blocking of surgical instruments occurs during the operation. In the past, mouth opening was defined as the distance between the incisor edges of the upper and lower central incisors when the patient opens his mouth widely, and the implant area could be in any missing tooth position. When it is in the posterior tooth area, the specific measurement scheme of the mouth opening could not be simply equivalent to the previous measurement method in the anterior tooth area. However, how to measure quickly and conveniently the mouth opening of any surgical area to determine whether it could be implanted and meet the needs of the selected guidance method remains unclear. This paper introduces new concepts, establishes new classification and corresponding accurate measurement scheme of implant area, and establishes a decision tree of implant methods guided by the actually measured value. Results provide a quantitative basis for rational formulation and implementation of implant treatment.

Changing landscape of paediatric refugee health in South Western Sydney, Australia: a retrospective observational study.

OBJECTIVES: To examine the changing health needs of refugee children and young people (CYP) entering Australia, in relation to key government policy changes. STUDY DESIGN: Retrospective analysis of health service use data over 11 years. SETTING: Paediatric refugee clinics in South Western Sydney (SWS), the Australian region with the largest annual resettlement of refugees. PARTICIPANTS: Refugee CYP (≤25 years) attending the SWS paediatric refugee clinics for their first visit between 2009 and 2019. MEASURES: Clinician defined health conditions categorised as communicable and non-communicable disease (NCD). RESULTS: Data were analysed for 359 CYP, mean age 9.3 years; 212 male (59.1%). Most CYP (n=331, 92.2%) had health problems identified; 292 (81.3%) had ≥1 NCD and 24 (6.7%) had ≥1 communicable disease. The most frequent individual NCDs were dental disease (n=128, 35.7%) and vitamin D deficiency (n=72, 20.1%). Trend analysis showed increased odds of identifying an NCD from 2013 onwards (crude OR 1.77, 95% CI 1.06 to 2.96). Neurodevelopmental problems, especially Global Developmental Delay (n=31, 8.6%), emerged as more prevalent issues in the latter half of the decade. There were significantly increased odds of identifying a neurodevelopmental problem in 2016-2019, especially in 2016-2017 (adjusted OR 2.93, 95% CI 1.34 to 6.40). Key policy changes during this period included acceptance of refugees with disabilities from 2012, additional Australian Humanitarian Programme intake from the Eastern Mediterranean region and mandatory offshore processing for those seeking asylum by boat from 2013. In response to the changing needs, local health services adopted nurse-led primary healthcare screening, early childhood services, youth and disability clinics. CONCLUSIONS: Refugee CYP in Australia are presenting with a growing burden of NCDs, with neurodevelopmental problems contributing. Government policy changes affect the sociodemographics of resettled populations, influencing health profiles. Paediatric refugee health services need to be responsive to the changing needs of these populations to optimise well-being.

Creating a Microenvironment to Give Wings to Dental Pulp Regeneration-Bioactive Scaffolds.

Dental pulp and periapical diseases make patients suffer from acute pain and economic loss. Although root canal therapies, as demonstrated through evidence-based medicine, can relieve symptoms and are commonly employed by dentists, it is still difficult to fully restore a dental pulp's nutrition, sensory, and immune-regulation functions. In recent years, researchers have made significant progress in tissue engineering to regenerate dental pulp in a desired microenvironment. With breakthroughs in regenerative medicine and material science, bioactive scaffolds play a pivotal role in creating a suitable microenvironment for cell survival, proliferation, and differentiation, following dental restoration and regeneration. This article focuses on current challenges and novel perspectives about bioactive scaffolds in creating a microenvironment to promote dental pulp regeneration. We hope our readers will gain a deeper understanding and new inspiration of dental pulp regeneration through our summary.

Simultaneous implantation and tooth preparation technology guided by 3D-printed guide.

Using digital technologies in concurrently performing missing tooth implantation and preparation of remaining teeth is a solution to reduce the number of visits and improve efficiency. This paper proposes a digital process for simultaneously implanting and preparing teeth. It integrates implant surgical guide and 3D-printed tooth preparation guide into a single guide and completes guided implant placement and precise tooth preparation. Based on "repair-oriented" virtual implant planning, the implant surgical guide can improve the efficiency and predictability of implant placement, and its linear accuracy is about 1 mm. The tooth preparation guide precisely guides tooth preparation and restoration space visualization, ensuring the quality of the tooth preparation. The two guides have different design accuracy requirements, and thus their combination improves the overall guiding accuracy requirements. The concurrent application of the two guides minimizes the clinical operation time, number of visits, and economic burden of patients.

Transcriptome landscape comparison of periodontium in developmental and renewal stages.

Objectives: Periodontium regeneration remains a significant challenge in clinics and research, and it is essential to understand the stage-specific biological process in situ. However, differing findings have been reported, and the mechanism has yet to be elucidated. The periodontium of adult mice molars is considered to be stable remodeling tissue. At the same time, the continuously growing incisors and the developing dental follicle (DF) of postnatal mice highly represent fast remodeling tissue. In this study, we attempted to explore different clues of temporal and spatial comparisons to provide improved references for periodontal regeneration. Methods: Periodontal tissues from the developing periodontium (DeP) of postnatal mice, and continuously growing periodontium (CgP) and stable remodeling periodontium (ReP) of adult mice were isolated and compared using RNA sequencing. Based on the Dep and CgP separately compared with the ReP, differentially expressed genes and signaling pathways were analyzed using GO, KEGG databases, and Ingenuity Pathway Analysis (IPA). The results and validation were obtained by immunofluorescence staining and RT-PCR assays. Data were expressed as means ± standard deviation (SD) and analyzed by GraphPad Prism 8 software package, and one-way ANOVA was used to test multiple groups. Results: Principal component analysis showed that the three groups of periodontal tissue were successfully isolated and had distinct expression profiles. A total of 792 and 612 DEGs were identified in the DeP and CgP groups compared with the ReP. Upregulated DEGs in the DeP were closely related to developmental processes, while the CgP showed significantly enhanced cellular energy metabolism. The DeP and CgP showed a common downregulation of the immune response, with activation, migration, and recruitment of immune cells. IPA and further validation jointly suggested that the MyD88/p38 MAPK pathway played an essential regulatory role in periodontium remodeling. Conclusion: Tissue development, energy metabolism, and immune response were critical regulatory processes during periodontal remodeling. Developmental and adult stages of periodontal remodeling showed different expression patterns. These results contribute to a deeper understanding of periodontal development and remodeling and may provide references for periodontal regeneration.

In vitro evaluation of periapical lesion-derived stem cells for dental pulp tissue engineering.

Dental pulp tissue engineering is a promising alternative treatment for pulpitis and periapical periodontitis, and dental pulp stem cells (DPSCs) are considered to be the gold standard for dental seed cell research. Periapical lesions harbor mesenchymal stem cells with the capacity for self-renewal and multilineage differentiation. However, it remains unknown whether these periapical lesion-derived stem cells (PLDSCs) are suitable for dental pulp tissue engineering. To investigate this possibility, PLDSCs and DPSCs were isolated using the tissue outgrowth method and cultured under identical conditions. We then performed in vitro experiments to investigate their biological characteristics. Our results indicate that PLDSCs proliferate actively in vitro and exhibit similar morphology, immunophenotype and multilineage differentiation ability as DPSCs. Simultaneously, PLDSCs exhibit stronger migrative ability and express more vascular endothelial growth factor and glial cell line-derived neurotrophic factor than DPSCs, and PLDSC-derived conditioned medium was more effective in tube formation assay. The mRNA expression levels of immunomodulatory genes HLA-G, IDO and ICAM-1 were also higher in PLDSCs. However, regarding osteo/odontogenic differentiation, PLDSCs showed weaker alkaline phosphatase staining and lower calcified nodule formation compared to DPSCs, as well as lower expression of ALP, RUNX2 and DSPP, as confirmed by a quantitative RT-PCR. The osteo/odontogenic protein expression levels of DSPP, RUNX2, DMP1 and SP7 were also higher in DPSCs. The present study demonstrates that PLDSCs demonstrate potential use as seed cells for dental pulp regeneration, especially for achieving enhanced neurovascularization.

The effect of TMJ disk repositioning by suturing through open incision on adolescent mandibular asymmetry with and without a functional orthodontic appliance.

OBJECTIVE: The objective of this study was to evaluate the effect of combined temporomandibular joint (TMJ) disk repositioning by suturing through open incision and orthodontic functional appliance (OFA) treatment for adolescents with mandibular asymmetry. STUDY DESIGN: Adolescent patients (12-20 years old) with mandibular asymmetry combined with unilateral TMJ disk displacement without reduction were treated with disk repositioning by suturing through open incision with and without postoperative OFA. Magnetic resonance imaging and posteroanterior cephalometric radiographs (PA) were used to measure and compare the changes in condylar height, joint space, and menton deviation pre- and postoperatively. RESULTS: Twenty-six patients were included in the study. Joint space was significantly increased postoperatively and new bone mostly formed at the superior or posterior superior part of the condyle after 6 to 18 months in all surgically treated joints. Fourteen patients with OFA had a significant increase in condylar height and menton deviation compared to 12 patients without OFA (2.29 ± 0.91 mm vs 1.22 ± 0.69 mm, P = .003; 4.56 ± 1.48 mm vs 2.01 ± 0.74 mm, P = .000). CONCLUSIONS: Combined treatment with TMJ disk repositioning by suturing through open incision and OFA can promote condylar growth and correct mandibular deviation in adolescent patients. Postoperative OFA can maintain the increased joint space created by disk repositioning and promote new bone formation at the superior and posterior parts of the condyle.

A more defective substrate leads to a less defective passive layer: Enhancing the mechanical strength, corrosion resistance and anti-inflammatory response of the low-modulus Ti-45Nb alloy by grain refinement.

Orthopedic and dental implants made of ß-type Ti alloys have low elastic modulus which can better relieve the stress shielding effects after surgical implantation. Nevertheless, clinical application of ß-type Ti alloys is hampered by the insufficient mechanical strength and gradual release of pro-inflammatory metallic ions under physiological conditions. In this study, the ß-type Ti-45Nb alloy is subjected to high-pressure torsion (HPT) processing to refine the grain size. After HPT processing, the tensile strength increases from 370 MPa to 658 MPa due to grain boundary strengthening and at the same time, the favorable elastic modulus is maintained at a low level of 61-72 GPa because the single ß-phase is preserved during grain refinement. More grain boundaries decrease the work function and facilitate the formation of thicker and less defective passive films leading to better corrosion resistance. In addition, more rapid repair of the passive layer mitigates release of metallic ions from the alloy and consequently, the inflammatory response is suppressed. The results reveal a strategy to simultaneously improve the mechanical and biological properties of metallic implant materials for orthopedics and dentistry. STATEMENT OF SIGNIFICANCE: The low modulus Ti-45Nb alloy is promising in addressing the complication of stress shielding induced by biomedical Ti-based materials with too-high elastic modulus. However, its insufficient strength hampers its clinical application, and traditional strengthening via heat treatments will compromise the low elastic modulus. In the current study, we enhanced the ultimate tensile strength of Ti-45Nb from 370 MPa to 658 MPa through grain-refinement strengthening, while the elastic modulus was maintained at a low value (61-72 GPa). Moreover, substrate grain-refinement has been proved to improve the corrosion resistance of Ti-45Nb with reduced inflammatory response both in vitro and in vivo. A relationship between the substrate microstructure and the surface passive layer has been established to explain the beneficial effects of substrate grain-refinement.

Enhanced interfacial adhesion and osseointegration of anodic TiO2 nanotube arrays on ultra-fine-grained titanium and underlying mechanisms.

The poor adhesion of anodic TiO2 nanotubes (TNTs) arrays on titanium (Ti) substrates adversely affects applications in many fields especially biomedical engineering. Herein, an efficient strategy is described to improve the adhesion strength of TNTs by performing grain refinement in the underlying Ti substrate via high-pressure torsion processing, as a larger number of grain boundaries can provide more interfacial mechanical anchorage. This process also improves the biocompatibility and osseointegration of TNTs by increasing the surface elastic modulus. The TNTs in length of 0.4 µm have significantly larger adhesion strength than the 2.0 µm long ones because the shorter TNTs experience less interfacial internal stress. However, post-anodization annealing reduces the fluorine concentration in TNTs and adhesion strength due to the formation of interfacial cavities during crystallization. The interfacial structure of TNTs/Ti system and the mechanism of adhesion failures are further investigated and discussed. STATEMENT OF SIGNIFICANCE: Self-assembled TiO2 nanotubes (TNTs) prepared by electrochemical anodization have a distinct morphology and superior properties, which are commonly used in photocatalytic systems, electronic devices, solar cells, sensors, as well as biomedical implants. However, the poor adhesion between the TNTs and Ti substrate has hampered wider applications. Here in this study, we describe an efficient strategy to improve the adhesion strength of TNTs by performing grain refinement in the underlying Ti substrate via high-pressure torsion (HPT) processing. The interfacial structure of TNTs/Ti system and the mechanism of adhesion failure are systematically studied and discussed. Our findings not only develop the knowledge of TNTs/Ti system, but also provide new insights into the design of Ti-based implants for orthopedic applications.

[Precise tooth preparation technique guided by 3D printing guide plate with quantitative hole].

The minimum amount of tooth preparation that can be fully controlled is crucial in achieving long-term, stable, and effective aesthetic restoration, which is also a major difficulty in aesthetic restoration. The tooth preparation can be imple-mented efficiently and accurately through digital technology based on the fixed-deep hole guiding technology. Prior the actual tooth preparation, the technology first designs the virtual contour, layering, and virtual occlusion of the prosthesis on the computer. Then, virtual tooth preparation is carried out by cutting back according to the virtual prosthesis. Next, the virtual drilling operation plan is designed according to the shape of the virtual tooth preparation and the contour of the abutment tooth. Finally, the tooth preparation guide plate is designed and printed in 3D. It realizes the whole process of quantitative and precise guidance of dental preparation, visualizes the restoration space, reduces the clinical operation time, and guarantees the quality of dental preparation. It also promotes the improvement of the teaching quality of digital practical exercises.

An electrospun fiber-covered stent with programmable dual drug release for endothelialization acceleration and lumen stenosis prevention.

Aneurysmal subarachnoid hemorrhage (SAH) causes high rates of mortality and morbidity. A covered stent is an effective endovascular treatment for complicated aneurysms intractable to endovascular coiling and surgical clipping. However, in-stent restenosis and delayed endothelialization are the main challenges contributing to its safety. In this study, we designed a biofunctional stent covered with dual drug-loaded electrospun fibers to achieve programmed vascular endothelial growth factor (VEGF) and paclitaxel (PTX) release for the early promotion of stent endothelialization and long-term inhibition of stenosis caused by smooth muscle hyperplasia. By encapsulating PTX-loaded mesoporous silica nanoparticles (MSNs) within electrospun polylactic acid (PLA) fibers, the release period of PTX was effectively extended. Furthermore, VEGF was conjugated onto the surface of the membrane by reacting with polydopamine (PDA) for quick release. The in vitro drug release profile revealed the sustained release of PTX, which persisted for 63 days without early burst release, while up to 87.05% of VEGF was rapidly released within 3 days. After 6 days of incubation, cell experiments demonstrated that the dual drug-loaded scaffold effectively prompted endothelial cell proliferation (488% vs. 386% in the control group, P = 0.001) and inhibited the proliferation of smooth muscle cells (SMCs) using the 21-day extracts (155% vs. 303% in the control group, P = 0.039). Animal studies showed that compared to bare stents, the drug-loaded covered stents improved the immediate- and mid-term complete aneurysm occlusion rates (P < 0.05). The drug-loaded covered stents also showed earlier endothelialization promotion and better lumen restenosis than normal covered stents (0% vs. 25%, P = 0.29) for 12 weeks. Overall, a programmed dual drug-loaded scaffold that effectively occluded the aneurysm sac was developed in this study, and the discrete release of VEGF and PTX promoted endothelialization and prevented in-stent stenosis. This study provided a new method to improve the biosafety of implanted covered stents for the treatment of intracranial aneurysms. STATEMENT OF SIGNIFICANCE: Aneurysmal subarachnoid hemorrhage (SAH) is one of the most common hemorrhage stroke resulted in a nearly 40% mortality and 33% morbidity due to sudden rupture of an intracranial aneurysm. Endovascular coil embolism is a popular treatment for aneurysm but this technique run high risk of bleeding, mass effect, low complete occlusion rate and higher recanalization rate due to its operation conducted within aneurysm sac. A bio-functional membrane knitted by dual-drug loaded electrospun fibers covered on a stent was designed to realize programed vascular endothelial growth factor and paclitaxel release for the early promotion of vascular endothelium and long-term inhibition of stenosis caused by smooth muscle hyperplasia. This study provides new method to improve the biosafety of covered stent insertion for the treatment of intracranial aneurysms.

Brain activation patterns during unilateral premolar occlusion.

OBJECTIVE: To observe the characteristics of brain activation during unilateral premolar occlusion. METHODS: Functional magnetic resonance imaging was collected from 10 healthy volunteers during occlusion of the left first premolar (L1), left second premolar (L2), and right first premolar (R1). The brain activation patterns were analyzed, and the primary sensorimotor cortex, supplementary motor area, insula, thalamus, and prefrontal cortex were chosen as regions of interest. RESULTS: Single premolar occlusion activated the precentral gyrus, postcentral gyrus, cerebellum, thalamus, frontal lobe, hippocampus, cingulate gyrus, and parietal lobe. The brain areas showing activation during single premolar occlusion were similar to those activated by chewing. The activation pattern of L1 was more similar to that of L2 than R1. No significant left and right hemisphere differences in signal intensity were detected within the regions of interest. CONCLUSION: Brain activation patterns from two ipsilateral premolars were more similar than the pattern from a contralateral premolar.

Three-Dimensional Printing of Biodegradable Piperazine-Based Polyurethane-Urea Scaffolds with Enhanced Osteogenesis for Bone Regeneration.

Synthetic biodegradable polymeric scaffolds with uniformly interconnected pore structure, appropriate mechanical properties, excellent biocompatibility, and even enhanced osteogenesis ability are urgently required for in situ bone regeneration. In this study, for the first time, a series of biodegradable piperazine (PP)-based polyurethane-urea (P-PUU) scaffolds with a gradient of PP contents were developed by air-driven extrusion 3D printing technology. The P-PUU ink of 60 wt % concentration was demonstrated to have appropriate viscosity for scaffold fabrication. The 3D-printed P-PUU scaffolds exhibited an interconnected porous structure of about 450 µm in macropore size and about 75% in porosity. By regulating the contents of PP in P-PUU scaffolds, their mechanical properties could be moderated, and P-PUU1.4 scaffolds with the highest PP contents exhibited the highest compressive modulus (155.9 ± 5.7 MPa) and strength (14.8 ± 1.1 MPa). Moreover, both in vitro and in vivo biological results suggested that the 3D-printed P-PUU scaffolds possessed excellent biocompatibility and osteoconductivity to facilitate new bone formation. The small molecular PP itself was confirmed for the first time to regulate osteogenesis of osteoblasts in a dose-dependent manner and the optimum concentration for osteoconductivity was about ∼0.5 mM, which suggests that PP molecules, together with the mechanical behavior, nitrogen-contents, and hydrophilicity of P-PUUs, play an important role in enhancing the osteoconductive ability of P-PUU scaffolds. Therefore, the 3D-printed P-PUU scaffolds, with suitable interconnected pore structure, appropriate mechanical properties, and intrinsically osteoconductive ability, should provide a promising alternative for bone regeneration.