Liposome-lentivirus for miRNA therapy with molecular mechanism study.

BACKGROUND: Cancer stem cells (CSCs) play a vital role in the occurrence, maintenance, and recurrence of solid tumors. Although, miR-145-5p can inhibit CSCs survival, poor understanding of the underlying mechanisms hamperes further therapeutic optimization for patients. Lentivirus with remarkable transduction efficiency is the most commonly used RNA carrier in research, but has shown limited tumor-targeting capability. METHODS: We have applied liposome to decorate lentivirus surface thereby yielding liposome-lentivirus hybrid-based carriers, termed miR-145-5p-lentivirus nanoliposome (MRL145), and systematically analyzed their potential therapeutic effects on liver CSCs (LCSCs). RESULTS: MRL145 exhibited high delivery efficiency and potent anti-tumor efficacy under in vitro and in vivo. Mechanistically, the overexpressed miR-145-5p can significantly suppress the self-renewal, migration, and invasion abilities of LCSCs by targeting Collagen Type IV Alpha 3 Chain (COL4A3). Importantly, COL4A3 can promote phosphorylating GSK-3ß at ser 9 (p-GSK-3ß S9) to inactivate GSK3ß, and facilitate translocation of ß-catenin into the nucleus to activate the Wnt/ß-catenin pathway, thereby promoting self-renewal, migration, and invasion of LCSCs. Interestingly, COL4A3 could attenuate the cellular autophagy through modulating GSK3ß/Gli3/VMP1 axis to promote self-renewal, migration, and invasion of LCSCs. CONCLUSIONS: These findings provide new insights in mode of action of miR-145-5p in LCSCs therapy and indicates that liposome-virus hybrid carriers hold great promise in miRNA delivery.

New frontiers in salivary extracellular vesicles: transforming diagnostics, monitoring, and therapeutics in oral and systemic diseases.

Salivary extracellular vesicles (EVs) have emerged as key tools for non-invasive diagnostics, playing a crucial role in the early detection and monitoring of diseases. These EVs surpass whole saliva in biomarker detection due to their enhanced stability, which minimizes contamination and enzymatic degradation. The review comprehensively discusses methods for isolating, enriching, quantifying, and characterizing salivary EVs. It highlights their importance as biomarkers in oral diseases like periodontitis and oral cancer, and underscores their potential in monitoring systemic conditions. Furthermore, the review explores the therapeutic possibilities of salivary EVs, particularly in personalized medicine through engineered EVs for targeted drug delivery. The discussion also covers the current challenges and future prospects in the field, emphasizing the potential of salivary EVs in advancing clinical practice and disease management.

Comparison of wall removal type versus wall retaining type of decompression for treating large mandibular odontogenic cysts.

OBJECTIVE: To evaluate the differences between two types of decompression for treating large mandibular odontogenic cysts. MATERIALS AND METHODS: This retrospective, cohort study included patients who were diagnosed for large mandibular odontogenic cysts from January 2015 to April 2018 and underwent two different types of decompression based on removal or retention of the cyst wall. The primary outcome was the percentage of the residual cyst area within 1 year after surgery. We used the propensity score matching (PSM) to balance the covariates of the two groups, and the primary outcome was analyzed by the non-inferiority test. RESULTS: A total of 93 cases were included in our study. After 1 year, the wall removal group was non-inferior to the wall retaining group in terms of cyst area, cyst volume, and the difference between the HU values of the original cyst region and the normal mandible. In subgroup analysis, we found there were no differences between two groups in the percentage of patients in whom the cystic area was reduced by 90% after 1 year. CONCLUSION: Our findings suggest that the wall removal group showed better results than the cyst wall retaining group in large mandibular odontogenic cysts.

Photoacoustic and Magnetic Resonance Imaging Bimodal Contrast Agent Displaying Amplified Photoacoustic Signal.

Progress in photoacoustic (PA) and magnetic resonance imaging (MRI) bimodal contrast agents has been achieved mainly by utilizing the imaging capability of single or multiple components and consequently realizing the desired application for both imaging modalities. However, the mechanism of the mutual influence between components within a single nanoformulation, which is the key to developing high-performance multimodal contrast agents, has yet to be fully understood. Herein, by integrating conjugated polymers (CPs) with iron oxide (IO) nanoparticles using an amphiphilic polymer, a bimodal contrast agent named CP-IO is developed, displaying 45% amplified PA signal intensity as compared to bare CP nanoparticle, while the performance of MRI is not affected. Further experimental and theoretical simulation results reveal that the addition of IO nanoparticles in CP-IO nanocomposites contributes to this PA signal amplification through a synergistic effect of additional heat generation and faster heat dissipation. Besides, the feasibility of CP-IO nanocomposites acting as PA-MRI bimodal contrast agents is validated through in vivo tumor imaging using mice models. From this study, it is demonstrated that a delicately designed structural arrangement of various components in a contrast agent could potentially lead to a superior performance in the imaging capability.

Association of Periodontitis with Rheumatoid Arthritis and the Effect of Non-Surgical Periodontal Treatment on Disease Activity in Patients with Rheumatoid Arthritis.

BACKGROUND The association of periodontitis (PD) with the prevalence of rheumatoid arthritis (RA) remains controversial. Therefore, the aim of this study was to evaluate their correlation and investigate the effects of non-surgical periodontal treatment on RA. MATERIAL AND METHODS A total of 64 patients were enrolled in this study and divided into 4 groups: 18 PD patients (PD+RA-), 18 RA patients (PD-RA+), 18 RA with PD patients (PD+RA+), and 10 healthy controls (PD-RA-). Periodontal and rheumatologic parameters were examined at baseline and 1 month following non-surgical periodontal treatment. RESULTS Our results showed that RA patients had similar periodontal status. However, patients in the PD+RA+ group had significantly higher levels of rheumatologic parameters such as C-reactive protein (CRP), anti-cyclic citrulline peptide antibody (ACPA), erythrocyte sedimentation rate (ESR), and Disease Activity Score 28 (DAS28) than those in the PD-RA+ group. In addition, non-surgical periodontal treatment was efficacious in improving rheumatologic parameters of patients in the PD+RA+ group. CONCLUSIONS The presence of PD might contribute to the progression of RA, while RA might have little effect on accelerating the development of PD. In addition, RA patients with PD receiving non-surgical periodontal treatment resulted in noteworthy improvement in the clinical outcome for RA.

A 6-month clinical evaluation of a high frequency sonic toothbrush in comparison with an oscillating-rotating power toothbrush and a traditional sonic toothbrush in reducing gingivitis and plaque.

PURPOSE: To compare the 6-month clinical efficacy of a novel high frequency sonic power toothbrush (A) with an oscillating-rotating (O-R) power toothbrush (B) and a traditional sonic toothbrush (C) in reducing plaque and gingivitis. METHODS: This was a single-center, randomized, examiner-blind, parallel group design consisting of two two-treatment sub-trials. Gingivitis was assessed using the Modified Gingival Index (MGI) and Gingival Bleeding Index (GBI). Plaque was assessed using the Rustogi Modified Navy Plaque Index (RMNPI) at Baseline, Month 3, and Month 6. Statistical analysis between A versus B and A versus C were evaluated. Data were analyzed using an ANCOVA with the baseline score as the covariate. RESULTS: In total, 120 subjects (40 per group) were randomized to treatments and 119 subjects completed the study. All power toothbrushes provided statistically significant reductions in gingivitis and plaque relative to Baseline (P< 0.001). Reductions in MGI and GBI scores were not statistically significantly different between A and B at Months 3 and 6. While A had statistically significant 20.1% and 29.0% greater reductions in total RMNPI and interproximal RMNPI respectively, compared to B at Month 6 (P< 0.05). Reductions in gingivitis and plaque indices were not statistically significantly different between A (41,000 oscillations/minute) and C (31,000 oscillations/minute) at Month 3. Compared to C, A demonstrated 14.0% and 14.5% greater reductions in MGI and GBI respectively, and 26.0% greater reduction in interproximal RMNPI versus baseline at Month 6 (P< 0.05). No adverse events were reported for the power toothbrushes. CLINICAL SIGNIFICANCE: The new high frequency sonic power toothbrush was not significantly different from the oscillating-rotating power toothbrush in gingivitis reduction while it demonstrated statistically significantly greater reductions in plaque. The new high frequency sonic power toothbrush was significantly more efficacious than the traditional sonic toothbrush in reducing plaque and gingivitis after long term use.

Physico-Chemical Processes.

This review covers research articles published in 2017 on topics relating to physico-chemical processes for water and wastewater treatment. The paper divides into nine sections, i. e., membrane technology, ion exchange, capacitive deionization, granular filtration, coagulation/flocculation, sedimentation, flotation, oxidation and adsorption. The membrane technology part includes six parts, including microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), reverse osmosis (RO), forward osmosis (FO), and membrane distillation (MD).

A Porphyrin-Based Conjugated Polymer for Highly Efficient In Vitro and In Vivo Photothermal Therapy.

Conjugated polymers have been increasingly studied for photothermal therapy (PTT) because of their merits including large absorption coefficient, facile tuning of exciton energy dissipation through nonradiative decay, and good therapeutic efficacy. The high photothermal conversion efficiency (PCE) is the key to realize efficient PTT. Herein, a donor-acceptor (D-A) structured porphyrin-containing conjugated polymer (PorCP) is reported for efficient PTT in vitro and in vivo. The D-A structure introduces intramolecular charge transfer along the backbone, resulting in redshifted Q band, broadened absorption, and increased extinction coefficient as compared to the state-of-art porphyrin-based photothermal reagent. Through nanoencapsulation, the dense packing of a large number of PorCP molecules in a single nanoparticle (NP) leads to favorable nonradiative decay, good photostability, and high extinction coefficient of 4.23 × 104 m-1 cm-1 at 800 nm based on porphyrin molar concentration and the highest PCE of 63.8% among conjugated polymer NPs. With the aid of coloaded fluorescent conjugated polymer, the cellular uptake and distribution of the PorCP in vitro can be clearly visualized, which also shows effective photothermal tumor ablation in vitro and in vivo. This research indicates a new design route of conjugated polymer-based photothermal therapeutic materials for potential personalized theranostic nanomedicine.

Broad Bandgap D-A Copolymer Based on Bithiazole Acceptor Unit for Application in High-Performance Polymer Solar Cells with Lower Fullerene Content.

A new broad bandgap and 2D-conjugated D-A copolymer, PBDTBTz-T, based on bithienyl-benzodithiophene donor unit and bithiazole (BTz) acceptor unit, is designed and synthesized for the application as donor material in polymer solar cells (PSCs). The polymer possesses highly coplanar and crystalline structure with a higher hole mobility and lower HOMO energy level which is beneficial to achieve higher open circuit voltage (Voc ) of the PSCs with the polymer as donor. The PSCs based on PBDTBTz-T:PC71 BM blend film with a lower PC71 BM content of 40% demonstrate a power conversion efficiency (PCE) of 6.09% with a relatively higher Voc of 0.92 V. These results indicate that the lower HOMO energy level of the BTz-based D-A copolymer is beneficial to a high Voc of the PSCs. The polymer, with highly coplanar and crystalline structure, can effectively reduce the content of fullerene acceptor in the active layer and can enhance the absorption and PCE of the PSCs.

JNK MAPK is involved in BMP-2-induced odontoblastic differentiation of human dental pulp cells.

Bone morphogenetic protein-2 (BMP-2) is a multi-functional growth factor belonging to the transforming growth factor ß superfamily that has a broad range of activities that affect many different cell types. BMP-2 induces odontoblastic differentiation of human dental pulp cells (DPCs), but the underlying mechanism remains unclear. In this study, we investigated the potential role of the JNK mitogen-activated protein kinases (MAPK) pathway in BMP-2-induced odontoblastic differentiation of DPCs. The levels of phosphorylated and unphosphorylated JNK MAPK were quantified by Western blot analysis following treatment with BMP-2 and the JNK inhibitor SP600125. The role of JNK MAPK in the BMP-2-induced odontoblastic differentiation of DPCs was determined by measuring alkaline phosphatase (ALP) activity and by examining the expression of odontoblastic markers using quantitative real-time polymerase chain reaction analysis. The effect of JNK MAPK silencing on odontoblastic differentiation was also investigated. BMP-2 upregulated the phosphorylation of JNK in DPCs in a dose- and time-dependent manner. Early markers of odontoblastic differentiation, including ALP activity, osteopontin and dentin matrix protein-1, were not inhibited by the JNK inhibitor. However, the JNK inhibitor, SP600125, significantly inhibited late-stage differentiation of odontoblasts, including the gene expression of osteocalcin, dentin sialophosphoprotein and bone sialoprotein, and also reduced the formation of mineralized nodules in BMP-2-treated DPCs. Consistent with this observation, silencing of JNK MAPK also decreased late-stage odontoblastic differentiation. Taken together, these findings suggest that JNK activity is required for late-stage odontoblastic differentiation induced by BMP-2.

Accuracy of using computer-aided rapid prototyping templates for mandible reconstruction with an iliac crest graft.

BACKGROUND: This study aimed to evaluate the accuracy of surgical outcomes in free iliac crest mandibular reconstructions that were carried out with virtual surgical plans and rapid prototyping templates. METHODS: This study evaluated eight patients who underwent mandibular osteotomy and reconstruction with free iliac crest grafts using virtual surgical planning and designed guiding templates. Operations were performed using the prefabricated guiding templates. Postoperative three-dimensional computer models were overlaid and compared with the preoperatively designed models in the same coordinate system. RESULTS: Compared to the virtual osteotomy, the mean error of distance of the actual mandibular osteotomy was 2.06 ± 0.86 mm. When compared to the virtual harvested grafts, the mean error volume of the actual harvested grafts was 1412.22 ± 439.24 mm3 (9.12% ± 2.84%). The mean error between the volume of the actual harvested grafts and the shaped grafts was 2094.35 ± 929.12 mm3 (12.40% ± 5.50%). CONCLUSIONS: The use of computer-aided rapid prototyping templates for virtual surgical planning appears to positively influence the accuracy of mandibular reconstruction.

Advancements in manganese complex-based MRI agents: Innovations, design strategies, and future directions.

This review focuses on the advancements in manganese (Mn) complex-based magnetic resonance imaging (MRI) agents for imaging different diseases. Here we emphasize the unique redox properties of Mn to deliver innovative MRI contrast agents, including small molecules, nanoparticles (NPs), metal-organic frameworks (MOFs), and polymer hybrids. Aspects of their rational design have been discussed, including size dependence, morphology tuning, surface property enhancement, etc., while also discussing the existing challenges and potential solutions. The present work will inspire and motivate scientists to emphasize MRI-guided applications and bring clinical success in the coming years.

Revealing the structural changes of lignin in Chinese quince (Chaenomeles sinensis) fruit as it matures.

Chinese quince fruits (Chaenomeles sinensis) contain substantial amounts of lignin; however, the exact structure of lignin remains to be investigated. In this study, milled wood lignins (Milled wood lignin (MWL)-1, MWL-2, MWL-3, MWL-4, MWL-5, and MWL-6) were extracted from fruits harvested once a month from May to October 2019 to investigate their structural evolution during fruit growth. The samples were characterized via High-performance anion exchange chromatography (HPAEC), Fourier transform-infrared spectroscopy (FT-IR), gel permeation chromatography (GPC), thermogravimetric (TGA), pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and NMR (2D-heteronuclear single quantum coherence (HSQC) and 31P). The MWL samples in all fruit growth stages were GS-type lignin and lignin core undergoing minimal alterations during fruit development. The predominant linkage in the lignin structure was ß-O-4', followed by ß-ß' and ß-5'. Galactose and glucose were the main monosaccharides associated with MWL. In MWL-6, the lignin exhibited the highest homogeneity and thermal stability. As the fruit matured, a gradual increase in the ß-O-4' proportion and the ratio of S/G was observed. The results provide comprehensive characterization of the cell wall lignin of quince fruit as it matures. This study could inspire innovative applications of quince fruit lignin and provide the optimal harvest time for lignin utilization.

NIR-II Excitable Water-Dispersible Two-Dimensional Conjugated Polymer Nanoplates for In Vivo Two-Photon Luminescence Bioimaging.

While two-dimensional conjugated polymers (2DCPs) have shown great promise in two-photon luminescence (TPL) bioimaging, 2DCP-based TPL imaging agents that can be excited in the second near-infrared window (NIR-II) have rarely been reported so far. Herein, we report two 2DCPs including 2DCP1 and 2DCP2, with octupolar olefin-linked structures for NIR-II-excited bioimaging. The 2DCPs are customized with the fully conjugated donor-acceptor (D-A) linkage and aggregation-induced emission (AIE) active building blocks, leading to good two-photon absorption into the NIR-II window with a 2PACS of ∼64.0 GM per choromophore for both 2DCPs. Moreover, 2DCP1 powders can be exfoliated into water-dispersible nanoplates with a Pluronic F-127 surfactant-assisted temperature-swing method, accompanied by both a drastic reduction of 2PACS throughout the range of 780-1080 nm and a sharp increase of photoluminescence quantum yield to 33.3%. The 2DCP1 nanoplates are subsequently proven to be capable of assisting in visualizing mouse brain vasculatures with a penetration depth of 421 µm and good contrast in vivo, albeit that only 19% of previous 2PACS at 1040 nm is preserved. This work not only provides important insights on how to construct NIR-II excitable 2DCPs for TPL bioimaging but also how to investigate the exfoliation-photophysical property correlation of 2DCPs, which should aid in future research on developing highly efficient TPL bioimaging agents.

[Effects of Polystyrene Microplastics on Growth, Physiology, Biochemistry, and Canopy Temperature Characteristics of Chinese Cabbage Pakchoi (Brassica chinensis L.)].

The aim of this study was to clarify the response characteristics of Chinese cabbage pakchoi (Brassica chinensis L.) under two particle size (100 nm and 1000 nm) polystyrene microplastic (PS-MPs) stress conditions. This study can provide a theoretical basis and experimental reference for the interpretation of the physiological and ecological mechanism of microplastic pollution and the bioremediation of microplastic-contaminated soil. Hydroponic experiments were carried out to study the effects of two particle sizes (100 nm and 1000 nm) of PS-MPs on growth, photosynthetic physiology, antioxidant enzyme activities, nutritional quality, anatomical structure, and canopy temperature in Chinese cabbage pakchoi. The results showed that PS-MPs stress significantly inhibited the growth and development of Chinese cabbage pakchoi. When PS-MPs stress was increased, the phenotypic indicators were significantly reduced. Meanwhile, PS-MPs stress significantly enhanced the oxidative stress response of Chinese cabbage pakchoi, such as the activities of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX) and the content of malondialdehyde (MDA) in leaves. Such a change tended to decrease the thickness of fenestrated and leaf and spongy tissues. Moreover, PS-MPs stress significantly increased the canopy population temperature of the Chinese cabbage pakchoi leaves. Microplastic stress had obvious inhibitory effects and toxic damage on the growth, development, and physical and chemical properties of Chinese cabbage pakchoi.

A state-of-the-art liposome technology for glioblastoma treatment.

Glioblastoma (GBM) is a challenging problem due to the poor BBB permeability of cancer drugs, its recurrence after the treatment, and high malignancy and is difficult to treat with the currently available therapeutic strategies. Furthermore, the prognosis and survival rate of GBM are still poor after surgical removal via conventional combination therapy. Owing to the existence of the formidable blood-brain barrier (BBB) and the aggressive, infiltrating nature of GBM growth, the diagnosis and treatment of GBM are quite challenging. Recently, liposomes and their derivatives have emerged as super cargos for the delivery of both hydrophobic and hydrophilic drugs for the treatment of glioblastoma because of their advantages, such as biocompatibility, long circulation, and ease of physical and chemical modification, which facilitate the capability of targeting specific sites, circumvention of BBB transport restrictions, and amplification of the therapeutic efficacy. Herein, we provide a timely update on the burgeoning liposome-based drug delivery systems and potential challenges in these fields for the diagnosis and treatment of brain tumors. Furthermore, we focus on the most recent liposome-based drug delivery cargos, including pH-sensitive, temperature-sensitive, and biomimetic liposomes, to enhance the multimodality in imaging and therapeutics of glioblastoma. Furthermore, we highlight the future difficulties and directions for the research and clinical translation of liposome-based drug delivery. Hopefully, this review will trigger the interest of researchers to expedite the development of liposome cargos and even their clinical translation for improving the prognosis of glioblastoma.

Circular RNA BIRC6 depletion promotes osteogenic differentiation of periodontal ligament stem cells via the miR-543/PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment.

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are the ideal seed cells for periodontal tissue regeneration. It is well established that persistent inflammation significantly impairs the osteogenic differentiation capability of PDLSCs. Therefore, maintaining PDLSC osteogenic potential under the inflammatory microenvironment is important for treating bone loss in periodontitis. The aim of our study was to explore the potential role of circular RNA BIRC6 (circBIRC6) in regulating osteogenic differentiation of PDLSCs in the inflammatory conditions. METHODS: Alkaline phosphatase staining, Alizarin Red staining, quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining were used to evaluated the effects of circBIRC6 on the osteogenic differentiation of PDLSCs. RNA pull-down and luciferase assays were performed to explore the interaction between circBIRC6 and miR-543. Then, the downstream signaling pathway affected by circBIRC6/miR-543 axis was further investigated. RESULTS: The expression level of circBIRC6 was higher in PDLSCs exposed to inflammatory stimulus and in periodontitis tissues compared to the respective controls. Downregulation of circBIRC6 enhanced the osteogenic potential of PDLSCs under the inflammatory conditions, and upregulation of circBIRC6 led to opposite findings. Mechanistically, we found that circBIRC6 modulated PDLSC osteogenic differentiation through sponging miR-543. More importantly, we have demonstrated that circBIRC6/miR-543 axis regulated the mineralization capacity of PDLSCs via PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment. CONCLUSIONS: In summary, the expression of miR-543 is significantly increased following circBIRC6 downregulation, leading to inhibition of PTEN and subsequently activation of PI3K/AKT/mTOR signaling pathway. Therefore, targeting circBIRC6 might represent a potential therapeutic strategy for improving bone loss in periodontitis.

Curative Effect of Yangxin Dingji Capsule Combined With Mexiletine Hydrochloride on Postoperative Arrhythmia and Its Influences on the Vascular Endothelial Function in Coronary Bifurcation Lesions.

Objective: The aim of the study is to explore the curative effect of Yangxin Dingji capsule combined with mexiletine hydrochloride on postoperative ventricular arrhythmia (VA) and its influences on vascular endothelial function in coronary bifurcation lesions (CBL). Methods: A total of 110 patients with CBL admitted to the hospital were enrolled as research subjects between January and December 2021. According to the random number table method, they were divided into a combination group and control group, with 55 cases in each group. The control group was treated with mexiletine hydrochloride, while the combination group was additionally treated with Yangxin Dingji capsules. All were continuously treated for 4 weeks. The clinical response rate between the two groups was compared. The frequencies of 24 h paroxysmal atrial fibrillation, premature atrial contraction, and premature ventricular contraction were compared by the Holter monitoring. The whole blood low-shear viscosity, whole blood high-shear viscosity, and fibrinogen (Fb) in both groups were measured by a full-automatic blood flow analyzer. The levels of plasma nitric oxide (NO), endothelin-1 (ET-1), and von Willebrand factor (vWF) were detected by the nitrate reductase method and enzyme-linked immunosorbent assay (ELISA). During treatment, the occurrence of adverse reactions (vomiting, loss of appetite, dry mouth, diarrhea, nausea) in both groups was statistically analyzed. Results: After treatment, the total response rate of treatment in the combination group was significantly higher than that in the control group (P < 0.05). After treatment, frequencies of paroxysmal atrial fibrillation, premature atrial contraction, and premature ventricular contraction in the combination group were significantly lower than those in the control group (P < 0.05). Whole blood low-shear viscosity, whole blood high-shear viscosity, and the Fb level were significantly lower than those in the control group (P < 0.05). After treatment, the NO level in the combination group was significantly higher than that in the control group (P < 0.05), while levels of ET-1 and vWF were significantly lower than those in the control group (P < 0.05). During treatment, there was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). Conclusion: Yangxin Dingji capsule combined with mexiletine hydrochloride can significantly improve clinical effects in CBL patients, improve VA and vascular endothelial function, and reduce plasma viscosity without increasing the incidence of adverse reactions.

Biomimetic and immunomodulatory baicalin-loaded graphene oxide-demineralized bone matrix scaffold for in vivo bone regeneration.

The use of an artificial bone substitute is a potential strategy for repairing bone defects; however, the inadequate consideration of repair-immune system interactions, resulting in significant pathological changes in the microenvironment, is a major barrier to achieving effective regenerative outcomes. Here, we evaluated a biomimetic baicalin (BAI)-incorporating graphene oxide-demineralized bone matrix (GO-BAI/DBM) hybrid scaffold, which was beneficial for bone regeneration. First, by considering that bone is a kind of organic-inorganic composite, a biomimetic GO/DBM bone substitute with enhanced physiochemical and osteoinductive properties was fabricated. Furthermore, inherently therapeutic GO was also used as a drug delivery carrier to achieve the sustained and prolonged release of BAI. Notably, a series of experiments showed that the GO-BAI nanocomposites could transform inflammatory M1 macrophages into pro-healing M2 macrophages, which was beneficial for in vitro angiogenesis and osteogenesis. By using a rat subcutaneous model, it was revealed that the GO-BAI nanocomposites proactively ameliorated the inflammatory response, which was coupled with decreased fibrous encapsulation. Notably, obvious in situ calvarial bone regeneration was achieved using the GO-BAI/DBM hybrid scaffold. These findings demonstrated that the bifunctional GO-BAI/DBM scaffold, by enhancing beneficial cross-talk among bone cells and inflammatory cells, might be utilized as an effective strategy for bone regeneration.

Asymmetric Silica Nanoparticles with Tailored Spiky Coverage Derived from Silica-Polymer Cooperative Assembly for Enhanced Hemocompatibility and Gene Delivery.

Asymmetric mesoporous silica nanoparticles (AMSNs) with one side featuring a spiky nanotopography, while the other side is smooth and solid, were synthesized via an ethylenediamine (EDA)-directed silica-polymer cooperative assembly approach. By simply varying the EDA amount (x), AMSNs-x samples with adjustable spiky surface coverage were obtained. It is demonstrated that a spiky coverage higher than 50% improved the hemocompatibility of AMSN-x, possibly due to the reduced contact area of the smooth side exposed to the red blood cell (RBC) membrane. Moreover, AMSNs-175 and AMSNs-200 with high spiky coverage enhanced their plasmid DNA (pDNA) loading and binding capability, as well as cellular uptake into HEK-293T cells, thus resulting in high transfection performance. The good hemocompatibility and high performance in pDNA delivery of AMSNs-x with high spiky coverage allow them to serve as promising nonviral vectors for potential applications in gene therapies and DNA vaccines.