Comparison of reconstruction plates and miniplates in mandibular defect reconstruction with free iliac flap.

OBJECTIVE: Given the increasing demand for precise and reliable reconstructive techniques in maxillofacial surgery, we try to offer valuable insights for clinicians in selecting optimal fixation methods. MATERIALS AND METHODS: Patients were categorized into miniplate and reconstruction plate groups for accuracy and bone healing comparison. We measured gonial angle, intercondylar, intergonial and anterior-posterior distance for general accuracy and distance of segmental endpoint to the sagittal plane for partial accuracy. The bone healing rate of the two groups was compared with CT images at 3, 6 and 12 months after operation. RESULT: Considering directional indicators, the miniplate group exhibited a wider intercondylar distance than the reconstruction plate group (p = 0.029). At 6 months postoperatively, the miniplate group demonstrated a higher bone healing rate compared to the reconstruction plate group, with no significant differences at other time points. CONCLUSION: Over a nearly 5-year review, mandibular reconstruction with vascularized iliac bone flaps showed that reconstruction plates better maintained condylar position accuracy, while miniplates had superior bone healing rates at 6 months. No significant differences were found in other accuracy indices between the two plates. CLINICAL RELEVANCE: Clinicians' selection of fixation plates frequently depends on personal preference rather than evidence-based criteria. This study compares the precision and postoperative osseous healing outcomes of miniplates and reconstruction plates to provide a more scientifically grounded basis for clinical decision-making.

Dynamic biomechanical changes of clear aligners during extraction space closure: Finite element analysis.

INTRODUCTION: Clear aligners (CAs) have recently become popular and widely used orthodontic appliances. Research on CA biomechanics has become a focal point in orthodontics to improve the efficiency of CA treatment and address challenging issues, such as extraction. The biomechanical characteristics of CAs in space closure have been reported. However, previous studies have mainly focused on static biomechanical analysis that cannot demonstrate the dynamic biomechanical changes in CAs during space-closing. Given that these biomechanical changes can be significant and have considerable clinical value, this study aimed to investigate these characteristics. METHODS: Sequential extraction space-closing models were derived from included patient data and refined using modeling and CA design software. A finite element analysis was performed to obtain biomechanical raw data. This study introduced a dual coordinate system and space geometry analysis to demonstrate the biomechanical properties accurately. RESULTS: As space closure progressed, the instantaneous tooth displacements increased, indicating an enhanced space closure force because of the increased strain in the CA extraction area. Meanwhile, the central axis of rotation of the anterior teeth continuously moved toward the labial-apical direction, showing a gradually enhanced vertical and torque control effect. CONCLUSIONS: During space closure, CAs undergo specific biomechanical changes, including increased contraction and control forces on both sides of the gap. These biomechanical effects are beneficial to alleviate the roller coaster effect gradually. Meanwhile, more reasonable staging design strategies can be proposed on the basis of this biomechanical mechanism.

Patients' perceptions matter: Risk communication and psychosocial factors in orthodontics.

INTRODUCTION: Effective risk communication is essential for achieving patient-centered oral health care, but the limited understanding of patients' subjective perceptions of orthodontic-related risks hinders this process. This study aimed to investigate adults' awareness, concerns, and risk-avoidance behaviors about long-term orthodontic risks, exploring their relationship with psychosocial factors. METHODS: We included 498 adult patients (mean age, 27.3 ± 6.8 years; women, 75.5%) during their initial visits to the orthodontic department at a hospital in Chengdu, China. Participants' understanding of orthodontic risks was gauged before and after exposure to the Oral Health Education Comics (OHEC), a specifically designed digital tool. Concurrently, we used logistic regression models to investigate the associations between patients' depression, anxiety, self-esteem, perfectionism, and dentofacial esthetics with risk perceptions. RESULTS: Approximately 79.5% of participants initially reported low awareness of orthodontic risks, with most knowledge from online sources. Notably, the percentage of participants with high awareness increased to 64.8% after OHEC. The negative facial soft-tissue change was most concerning for participants: 53.4% showed high concerns, and 28.1% showed high avoidance. Furthermore, linear regression indicated positive associations between depression (ß = 0.42 [95% confidence interval {CI}, 0.07-0.77]) and anxiety (ß = 0.76 [95% CI, 0.35-1.18]) with orthodontic risk concerns, whereas risk avoidance was positively associated with depression (ß = 0.62 [95% CI, 0.27-0.97]), anxiety (ß = 1.09 [95% CI, 0.68-1.50]), and perfectionism (ß = 0.24 [95% CI, 0.02-0.46]). CONCLUSIONS: Findings emphasize the imperative of streamlined risk communication in orthodontics. By incorporating comprehensible tools such as OHEC and integrating psychosocial evaluations, more refined patient-practitioner communication and psychosomatic-based dental care can be achieved.

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Pulpitis, periodontitis, jaw bone defect, and temporomandibular joint damage are common oral and maxillofacial diseases in clinic, but traditional treatments are unable to restore the structure and function of the injured tissues. Due to their good biocompatibility, biodegradability, antioxidant effect, anti-inflammatory activity, and broad-spectrum antimicrobial property, chitosan-based hydrogels have shown broad applicable prospects in the field of oral tissue engineering. Quaternization, carboxymethylation, and sulfonation are common chemical modification strategies to improve the physicochemical properties and biological functions of chitosan-based hydrogels, while the construction of hydrogel composite systems via carrying porous microspheres or nanoparticles can achieve local sequential delivery of diverse drugs or bioactive factors, laying a solid foundation for the well-organized regeneration of defective tissues. Chemical cross-linking is commonly employed to fabricate irreversible permanent chitosan gels, and physical cross-linking enables the formation of reversible gel networks. Representing suitable scaffold biomaterials, several chitosan-based hydrogels transplanted with stem cells, growth factors or exosomes have been used in an attempt to regenerate oral soft and hard tissues. Currently, remarkable advances have been made in promoting the regeneration of pulp-dentin complex, cementum-periodontium-alveolar bone complex, jaw bone, and cartilage. However, the clinical translation of chitosan-based hydrogels still encounters multiple challenges. In future, more in vivo clinical exploration under the conditions of oral complex microenvironments should be performed, and the combined application of chitosan-based hydrogels and a variety of bioactive factors, biomaterials, and state-of-the-art biotechnologies can be pursued in order to realize multifaceted complete regeneration of oral tissue.

Dual-Loaded Liposomes Tagged with Hyaluronic Acid Have Synergistic Effects in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most lethal subtypes of breast cancer. Although chemotherapy is considered the most effective strategy for TNBC, most chemotherapeutics in current use are cytotoxic, meaning they target antiproliferative activity but do not inhibit tumor cell metastasis. Here, a TNBC-specific targeted liposomal formulation of epalrestat (EPS) and doxorubicin (DOX) with synergistic effects on both tumor cell proliferation and metastasis is described. These liposomes are biocompatible and effectively target tumor cells owing to hyaluronic acid (HA) modification on their surface. This active targeting, mediated by CD44-HA interaction, allows DOX and EPS to be delivered simultaneously to tumor cells in vivo, where they suppress not only TNBC tumor growth and the epithelial-mesenchymal transition, but also cancer stem cells, which collectively suppress tumor growth and metastasis of TNBC and may also act to prevent relapse of TNBC.

Development of a powerful synthetic hybrid promoter to improve the cellulase system of Trichoderma reesei for efficient saccharification of corncob residues.

BACKGROUND: The filamentous fungus Trichoderma reesei is a widely used workhorse for cellulase production in industry due to its prominent secretion capacity of extracellular cellulolytic enzymes. However, some key components are not always sufficient in this cellulase cocktail, making the conversion of cellulose-based biomass costly on the industrial scale. Development of strong and efficient promoters would enable cellulase cocktail to be optimized for bioconversion of biomass. RESULTS: In this study, a synthetic hybrid promoter was constructed and applied to optimize the cellulolytic system of T. reesei for efficient saccharification towards corncob residues. Firstly, a series of 5' truncated promoters in different lengths were established based on the strong constitutive promoter Pcdna1. The strongest promoter amongst them was Pcdna1-3 (- 640 to - 1 bp upstream of the translation initiation codon ATG), exhibiting a 1.4-fold higher activity than that of the native cdna1 promoter. Meanwhile, the activation region (- 821 to - 622 bp upstream of the translation initiation codon ATG and devoid of the Cre1-binding sites) of the strong inducible promoter Pcbh1 was cloned and identified to be an amplifier in initiating gene expression. Finally, this activation region was fused to the strongest promoter Pcdna1-3, generating the novel synthetic hybrid promoter Pcc. This engineered promoter Pcc drove strong gene expression by displaying 1.6- and 1.8-fold stronger fluorescence intensity than Pcbh1 and Pcdna1 under the inducible condition using egfp as the reporter gene, respectively. Furthermore, Pcc was applied to overexpress the Aspergillus niger ß-glucosidase BGLA coding gene bglA and the native endoglucanase EG2 coding gene eg2, achieving 43.5-fold BGL activity and 1.2-fold EG activity increase, respectively. Ultimately, to overcome the defects of the native cellulase system in T. reesei, the bglA and eg2 were co-overexpressed under the control of Pcc promoter. The bglA-eg2 double expression strain QPEB70 exhibited a 178% increase in total cellulase activity, whose cellulase system displayed 2.3- and 2.4-fold higher saccharification efficiency towards acid-pretreated and delignified corncob residues than the parental strain, respectively. CONCLUSIONS: The synthetic hybrid promoter Pcc was generated and employed to improve the cellulase system of T. reesei by expressing specific components. Therefore, construction of synthetic hybrid promoters would allow particular cellulase genes to be expressed at desired levels, which is a viable strategy to optimize the cellulolytic enzyme system for efficient biomass bioconversion.

Comparative Analysis of Herbaceous and Woody Cell Wall Digestibility by Pathogenic Fungi.

Fungal pathogens have evolved combinations of plant cell-wall-degrading enzymes (PCWDEs) to deconstruct host plant cell walls (PCWs). An understanding of this process is hoped to create a basis for improving plant biomass conversion efficiency into sustainable biofuels and bioproducts. Here, an approach integrating enzyme activity assay, biomass pretreatment, field emission scanning electron microscopy (FESEM), and genomic analysis of PCWDEs were applied to examine digestibility or degradability of selected woody and herbaceous biomass by pathogenic fungi. Preferred hydrolysis of apple tree branch, rapeseed straw, or wheat straw were observed by the apple-tree-specific pathogen Valsa mali, the rapeseed pathogen Sclerotinia sclerotiorum, and the wheat pathogen Rhizoctonia cerealis, respectively. Delignification by peracetic acid (PAA) pretreatment increased PCW digestibility, and the increase was generally more profound with non-host than host PCW substrates. Hemicellulase pretreatment slightly reduced or had no effect on hemicellulose content in the PCW substrates tested; however, the pretreatment significantly changed hydrolytic preferences of the selected pathogens, indicating a role of hemicellulose branching in PCW digestibility. Cellulose organization appears to also impact digestibility of host PCWs, as reflected by differences in cellulose microfibril organization in woody and herbaceous PCWs and variation in cellulose-binding domain organization in cellulases of pathogenic fungi, which is known to influence enzyme access to cellulose. Taken together, this study highlighted the importance of chemical structure of both hemicelluloses and cellulose in host PCW digestibility by fungal pathogens.

Quantitative Proteome Profiling Reveals Cellobiose-Dependent Protein Processing and Export Pathways for the Lignocellulolytic Response in Neurospora crassa.

Filamentous fungi are intensively used for producing industrial enzymes, including lignocellulases. Employing insoluble cellulose to induce the production of lignocellulases causes some drawbacks, e.g., a complex fermentation operation, which can be overcome by using soluble inducers such as cellobiose. Here, a triple ß-glucosidase mutant of Neurospora crassa, which prevents rapid turnover of cellobiose and thus allows the disaccharide to induce lignocellulases, was applied to profile the proteome responses to cellobiose and cellulose (Avicel). Our results revealed a shared proteomic response to cellobiose and Avicel, whose elements included lignocellulases and cellulolytic product transporters. While the cellulolytic proteins showed a correlated increase in protein and mRNA levels, only a moderate correlation was observed on a proteomic scale between protein and mRNA levels (R2 = 0.31). Ribosome biogenesis and rRNA processing were significantly overrepresented in the protein set with increased protein but unchanged mRNA abundances in response to Avicel. Ribosome biogenesis, as well as protein processing and protein export, was also enriched in the protein set that showed increased abundance in response to cellobiose. NCU05895, a homolog of yeast CWH43, is potentially involved in transferring a glycosylphosphatidylinositol (GPI) anchor to nascent proteins. This protein showed increased abundance but no significant change in mRNA levels. Disruption of CWH43 resulted in a significant decrease in cellulase activities and secreted protein levels in cultures grown on Avicel, suggesting a positive regulatory role for CWH43 in cellulase production. The findings should have an impact on a systems engineering approach for strain improvement for the production of lignocellulases.IMPORTANCE Lignocellulases are important industrial enzymes for sustainable production of biofuels and bio-products. Insoluble cellulose has been commonly used to induce the production of lignocellulases in filamentous fungi, which causes a difficult fermentation operation and enzyme loss due to adsorption to cellulose. The disadvantages can be overcome by using soluble inducers, such as the disaccharide cellobiose. Quantitative proteome profiling of the model filamentous fungus Neurospora crassa revealed cellobiose-dependent pathways for cellulase production, including protein processing and export. A protein (CWH43) potentially involved in protein processing was found to be a positive regulator of lignocellulase production. The cellobiose-dependent mechanisms provide new opportunities to improve the production of lignocellulases in filamentous fungi.

Orthodontic compressive force modulates Ets-1/Tks5 pathway to promote the formation of circumferential invadopodia and the fusion of osteoclast precursors.

During orthodontic treatment a mechanical force is applied to the teeth. However, it remains unclear how mechanical force promotes the maturation and fusion of osteoclast precursors into osteoclasts. In this study, we aimed to explore the mechanism by which orthodontic compressive force promotes osteoclast maturation. We used a RAW264.7 macrophage-like cell line derived from Balb/c mice as the experimental model. We found that compressive force promoted the maturation of osteoclasts based on tartrate-resistant acid phosphatase staining and the formation of invadopodia based on immunstaining of Tks5 and F-actin. Moreover, we found that compressive force upregulated the expression of Ets-1 and Tks5 and promoted the activation of Ets-1 in RAW264.7 cells. Furthermore, we identified Tks5 as a transcription target of Ets-1 in RAW264.7 cells and demonstrated that Ets-1 mediates the effects of compressive force on Tks5 upregulation, invadopodia formation and cell fusion in osteoclasts. In conclusion, Ets-1 is upregulated by compressive force and it is essential to transducing the mechanical signal to promote invadopodia formation and osteoclast fusion. Our findings provide novel insight into the mechanism underlying osteoclast maturation and fusion during orthodontic treatment.

A ROS-responsive polymeric prodrug nanosystem with self-amplified drug release for PSMA (-) prostate cancer specific therapy.

BACKGROUND: The selectively accumulate in tumor site and completely release drug within cancer cells great limit the therapeutic effect of nano-drug delivery system. Moreover, absence of appropriate biomarker is one of the major challenges for prostate specific membrane antigen negative (PSMA (-)) prostate cancer therapy. RESULTS: Herein, a PSMA (-) prostate cancer specific targeted and intracellular reactive oxygen species (ROS) amplification for ROS-responsive self-accelerating drug release nanoplatform (ATD-NPs) was developed. ATD-NPs was formed by three parts, including PSMA (-) prostate cancer specifically targeted part (DUP-PEG-DSPE), ROS-sensitive doxorubicin (DOX) polymeric prodrug (P(L-TK-DOX)), and the ROS generation agent (α-tocopheryl succinate, α-TOS); and this delivery system is expected to enhance PSMA (-) prostate cancer therapeutic effect, increase selective accumulation at tumor site and overcome intracellular incomplete drug release. After administration i.v injection, ATD-NPs could specifically accumulate in tumor site and markedly be internalized by cancer cells based on the DUP-1 (a PSMA (-) cancer cells specific target peptide). Subsequently, ATD-NPs could be dissociated under the high concentration reactive oxygen species (ROS) condition, resulting in DOX and α-TOS release. Then, the released α-TOS could be reacted with mitochondria to produce ROS, which in turn accelerating the release of drugs. Finally achieved the purpose of enhancing therapeutic efficacy and reducing side effect. Both in vitro and in vivo experiments demonstrated that the combination of tumor actively-targeted and self-amplifying ROS-responsive drug release showed more significant antitumor activity in the human PSMA (-) prostate cancer. CONCLUSION: The described technology unifies the tumor actively targets, self-amplified drug release, and excellent biocompatibility into one formulation, are promising for cancer treatment.

The effect of cyclic tensile force on the actin cytoskeleton organization and morphology of human periodontal ligament cells.

To explore Girdin/Akt pathway protein expression and morphology change by cyclic tension in the periodontal ligament cells. Human periodontal ligament cells were exposed to cyclic tension force at 4000 µstrain and 0.5 Hz for 6 h though a four-point bending system. Cyclic tension force upregulated F-actin, Girdin and Akt expression in hPDL. In transmission electron microscope assay showed that there are more and bigger mitochondria, more and longer cynapses, more cellular organisms after tension force stimulation than control. The actin filament was changed to be regular lines and pointed to poles of cells. However, we found that the Girdin-depleted cells are small and there are more micro-organisms including more lysosomes and matrix vesicles than control. These finding suggest that the STAT3/Girdin/Akt pathway in PDL to response to mechanical stimulation as well, and Girdin may play a significant role in triggering cell proliferation and migration during orthodontic treatment. It provided an insight into the molecular basis for development of a vitro cell model in studying orthodontic treatment.

Socio-demographic factors, dental status and health-related behaviors associated with geriatric oral health-related quality of life in Southwestern China.

BACKGROUND: The aging of Chinese society has increased interest in improving the health-related quality of life (HRQoL) of the elderly, including their oral health-related quality of life (OHRQoL). This study aims to evaluate the OHRQoL of elders living in Sichuan Province (China) and to explore the explanatory factors of their OHRQoL. METHODS: A cross-sectional study conducted in 2016 in the Sichuan Province analyzed data from 744 elders, aged 65 to 74 years (mean age 69.3, 51.3% female). Clinical examinations and questionnaires were completed to collect information on the participants' socio-demographic characteristics, health-related behaviors, dental status, subjective health conditions and General Oral Health Assessment Index (GOHAI) score. RESULTS: The mean GOHAI score was 48.23 (SD 7.62), and the median score was 49. After adjustment for age and gender, the multiple linear regression analysis showed that participants who were female, had fair or poor self-rated oral health, decayed, missing and filled teeth (DMFT) score ≥ 20, fair or poor self-rated general health, and ≥ 2 teeth with root caries had worse OHRQoL, and participants who were edentulous had better OHRQoL (F = 29.58, p < 0.001). CONCLUSION: The OHRQoL of the elders living in Sichuan Province was relatively good. The explanatory variables were gender; self-rated oral health; DMFT score; self-rated general health; number of natural teeth; and number of teeth with root caries. More attention should be paid to caries status and retention of healthy teeth to improve the OHRQoL of elders in Sichuan Province, preserving a healthy mouth contributes to better OHRQoL.

Chimeric Protein Template-Induced Shape Control of Bone Mineral Nanoparticles and Its Impact on Mesenchymal Stem Cell Fate.

Protein-mediated molecular self-assembly has become a powerful strategy to fabricate biomimetic biomaterials with controlled shapes. Here we designed a novel chimeric molecular template made of two proteins, silk fibroin (SF) and albumin (ALB), which serve as a promoter and an inhibitor for hydroxyapatite (HA) formation, respectively, to synthesize HA nanoparticles with controlled shapes. HA nanospheres were produced by the chimeric ALB-SF template, whereas HA nanorods were generated by the SF template alone. The success in controlling the shape of HA nanoparticles allowed us to further study the effect of the shape of HA nanoparticles on the fate of rat mesenchymal stem cells (MSCs). We found that the nanoparticle shape had a crucial impact on the cellular uptake and HA nanospheres were internalized in MSCs at a faster rate. Both HA nanospheres and nanorods showed no significant influence on cell proliferation and migration. However, HA nanospheres significantly promoted the osteoblastic differentiation of MSCs in comparison to HA nanorods. Our work suggests that a chimeric combination of promoter and inhibitor proteins is a promising approach to tuning the shape of nanoparticles. It also sheds new light into the role of the shape of the HA nanoparticles in directing stem cell fate.

Electrochemical sensor for determination of tulathromycin built with molecularly imprinted polymer film.

A novel tulathromycin (TLTMC) electrochemical sensor based on molecularly imprinted polymer (MIP) membranes was constructed. p-Aminothiophenol (p-ATP) and TLTMC were assembled on the surface of gold nanoparticles (AuNPs) modified on the gold electrode (GE) by the formation of Au-S bonds and hydrogen-bonding interactions. Besides, polymer membranes were formed by electropolymerization in a polymer solution containing p-ATP, tetrachloroaurate(III) acid (HAuCl4), tetrabutylammonium perchlorate (TBAP), and a template molecule TLTMC. A novel molecular imprinted sensor (MIS) in this experiment was achieved after the removal of TLTMC. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements were used to illustrate the process of electropolymerization and its optimal conditions. The electrode with MIP obtained the linear of response range, which was between 3.0 × 10(-12) mol L(-1) and 7.0 × 10(-9) mol L(-1), and the limit of detection was 1.0 × 10(-12) mol L(-1). All the obtained results indicate that the MIS tends to be an effective electrochemical technique for the determination of TLTMC in real-time and in a complicated matrix.

A monetite/amorphous silica complex for long-term dentine hypersensitivity treatment through the acid stability and mineralization promoting effect of silica.

Dentine hypersensitivity (DH) is often related to the exposure of dentin tubules. Mineral particles, such as hydroxyapatite and bioactive glass, can provide calcium and phosphate ions to temporarily block dentin tubules via the biomineralization process, serving as feasible alternatives for DH treatment. However, due to the acidic microenvironment caused by dietary acids, these particles are easily eroded and dissolved, making it difficult to achieve efficient dentin tubule occlusion. Given the significant stability of silica in dietary acids and its excellent ability to bond with calcium and phosphate ions to form mineralized hydroxyapatite, we proposed to develop a micron-sized monetite/amorphous silica complex (MMSi) hydrosol to effectively seal the exposed dentin tubules. In this study, we hypothesized that the MMSi hydrosol could tolerate acid erosion and concurrently provide active sites for the calcium and phosphate ions to promote biomineralization in comparison to a micron-sized monetite (MM) hydrosol. Hence, the composition and microstructure including the surface morphology, silica content and phase composition of MMSi were investigated to verify the presence of silica. The results of the ion release and in vitro biomineralization process indicated that silica did not hinder the calcium and phosphate ion release and the formation of hydroxyapatite via the biomineralization process. The acid-resistant test suggested that the MMSi hydrosol exhibited a significantly slower corrosion rate than the MM hydrosol when treated with citric acid. Notably, the silica in the MMSi hydrosol retained the ability to induce the nucleation and crystallization of hydroxyapatite during de/remineralization processes. Finally, the MMSi hydrosol was mixed with commercialized toothpaste to explore its efficacy in dentin tubule occlusion via cycling de/remineralization processes. As a result, compared to the MM hydrosol, the toothpaste containing the MMSi hydrosol presented excellent acid-resistant ability and dentin tubule occlusion outcomes, which indicated that the MMSi hydrosol could be a potential promise in the long-term treatment of DH.

Multifunctional Exosomes Derived from M2 Macrophages with Enhanced Odontogenesis, Neurogenesis and Angiogenesis for Regenerative Endodontic Therapy: An In Vitro and In Vivo Investigation.

INTRODUCTION: Exosomes derived from M2 macrophages (M2-Exos) exhibit tremendous potential for inducing tissue repair and regeneration. Herein, this study was designed to elucidate the biological roles of M2-Exos in regenerative endodontic therapy (RET) compared with exosomes from M1 macrophages (M1-Exos). METHODS: The internalization of M1-Exos and M2-Exos by dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) was detected by uptake assay. The effects of M1-Exos and M2-Exos on DPSC and HUVEC behaviors, including migration, proliferation, odonto/osteogenesis, neurogenesis, and angiogenesis were determined in vitro. Then, Matrigel plugs incorporating M2-Exos were transplanted subcutaneously into nude mice. Immunostaining for vascular endothelial growth factor (VEGF) and CD31 was performed to validate capillary-like networks. RESULTS: M1-Exos and M2-Exos were effectively absorbed by DPSCs and HUVECs. Compared with M1-Exos, M2-Exos considerably facilitated the proliferation and migration of DPSCs and HUVECs. Furthermore, M2-Exos robustly promoted ALP activity, mineral nodule deposition, and the odonto/osteogenic marker expression of DPSCs, indicating the powerful odonto/osteogenic potential of M2-Exos. In sharp contrast with M1-Exos, which inhibited the neurogenic capacity of DPSCs, M2-Exos contributed to a significantly augmented expression of neurogenic genes and the stronger immunostaining of Nestin. Consistent with remarkably enhanced angiogenic markers and tubular structure formation in DPSCs and HUVECs in vitro, the employment of M2-Exos gave rise to more abundant vascular networks, dramatically higher VEGF expression, and widely spread CD31+ tubular lumens in vivo, supporting the enormous pro-angiogenic capability of M2-Exos. CONCLUSIONS: The multifaceted roles of M2-Exos in ameliorating DPSC and HUVEC functions potentially contribute to complete functional pulp-dentin complex regeneration.

Exosomes as Promising Therapeutic Tools for Regenerative Endodontic Therapy.

Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.

Preparation and properties of polyvinyl alcohol/chitosan-based hydrogel with dual pH/NH3 sensor for naked-eye monitoring of seafood freshness.

To address the issue of food spoilage causing health and economic loss, we developed a pH/NH3 dual sensitive hydrogel based on polyvinyl alcohol/chitosan (PVA/CS) containing chitosan-phenol red (CP). The CP was synthesized via Mannich reaction and immobilized it in PVA/CS hydrogel through freezing/thawing method to prepare the final PVA/CS/CP hydrogel. The synthesis of CP was confirmed by 1H NMR, FT-IR, XRD, UV-vis, and XPS. The characteristics of hydrogel were evaluated by FT-IR, XRD, SEM, mechanical properties, thermal stability, leaching, and color stability tests. The PVA/CS/CP hydrogel showed distinctly different color at various pH and NH3 vapor levels (yellow to purple). The hydrogel exhibited obvious color changes (ΔE = 46.95) in response to shrimp spoilage, stored at 4 °C. It showed positive and strong correlation between the ΔE values of the indicator hydrogel and total volatile basic nitrogen (TVB-N) as (R2 = 0.9573) and with pH as (R2 = 0.8686), respectively. These results clearly show that the PVA/CS/CP hydrogel could be applied for naked-eye real-time monitoring of seafood freshness in intelligent packaging.

Fabrication of a Nanoscale Magnesium/Copper Metal-Organic Framework on Zn-Based Guided Bone Generation Membranes for Enhancing Osteogenesis, Angiogenesis, and Bacteriostasis Properties.

Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal-organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu2+. As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn2+, Mg2+, and Cu2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.

A chitosan-based hydrogel loaded with fenofibrate for diabetic wound healing.

Diabetic wounds represent a common chronic condition, posing significant challenges in the treatment process due to bacterial infections, increased generation of reactive oxygen species (ROS) and exacerbated inflammation. Fenofibrate (FEN) is a clinical medication used for lipid regulation. In this study, it was utilized for the first time as an effective component of wound dressings for treating diabetic ulcers, exploring its novel applications further. Therefore, we prepared a polyvinyl alcohol/chitosan/FEN (PCF) hydrogel using a freeze-thaw method and conducted physicochemical characterization of the PCF hydrogel to further elucidate its biological functions. In vitro studies demonstrated that the PCF hydrogel exhibits excellent biocompatibility along with significant antimicrobial, pro-angiogenic, ROS-scavenging, and anti-inflammatory properties. Subsequent animal experiments indicated that the PCF hydrogel has the ability to promote blood vessel formation and collagen deposition. Additionally, the PCF hydrogel showed a significant inhibitory effect on the inflammatory response, as evidenced by the reductions in the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These compelling findings accentuate the promising application of the PCF hydrogel in the treatment of diabetic wounds.