Association between sugar-sweetened beverages and pure fruit juice with risk of six cardiovascular diseases: a Mendelian randomization study.

BACKGROUND: In observational and prospective cohort studies, intake of sugar-sweetened beverages (SSBs) and pure fruit juice (PFJ) has been associated with cardiovascular disease (CVD). Still, the causality of the connection has not yet been determined. Our objective was to uncover the relationship between SSBs/PFJ and CVD. METHODS: Genetically predicted causal associations between SSBs/PFJ (obtained in a published genome-wide association study) and six common CVDs (atrial fibrillation (AF), angina, heart failure (HF), acute myocardial infarction, hypertension, and coronary atherosclerosis) were assessed using MR analytic modeling. The primary analysis method utilized was the inverse variance weighted (IVW) method, complemented by additional methods such as the weighted median method, MR Egger regression, Cochran's Q test, MR pleiotropy residual, funnel plot, Bonferroni correction, and others for MR analysis. To ensure the robustness of the findings, F-values were calculated as a complementary test to set looser thresholds for exposing genetic instrumental variables (P < 1e-5). RESULTS: The results of MR analysis suggested genetically causal associations between SSBs and AF (odds ratio (OR): 1.023; 95% confidence interval (CI) 1.007-1.038; P = 0.0039) as well as between PFJ and angina (OR: 0.968; 95% CI, 0.943-0.993; P = 0.0138) there was genetic causality. However, MR analysis showed no causal association between SSBs/PFJ and other CVD risks. CONCLUSION: This study suggests that there may be a potential causal relationship between SSBs intake and AF and a causal negative association between PFJ intake and angina.

Craniocervical posture in patients with skeletal malocclusion and its correlation with craniofacial morphology during different growth periods.

The association between craniocervical posture and craniofacial structures in the various sagittal skeletal malocclusion during different growth stages has been the focus of intense interest in fields of orthodontics, but it has not been conclusively demonstrated. Thus, this study aimed to investigate the association between craniofacial morphology and craniocervical posture in patients with sagittal skeletal malocclusion during different growth periods. A total of 150 from a large pool of cephalograms qualified for the inclusion and exclusion were evaluated and classified into three groups according to the Cervical Vertebral Maturation (CVM) by examining the morphological modifications of the second through fourth cervical vertebrae, each group consisted of 50 cephalograms. In each growth period, for the comparison of head and cervical posture differences among various skeletal classes, the radiographs were further subdivided into skeletal Class I (0° < ANB < 5°, n = 16), skeletal Class II (ANB ≥ 5°, n = 18), and skeletal Class III (0° ≤ ANB, n = 16) on the basis of their ANB angle. There was no significant difference in gender (P > 0.05). Some variables were found to be significant during pubertal growth and later in patients with sagittal skeletal malocclusion (P < 0.05). Most indicators describing craniocervical posture were largest in skeletal Class II and smallest in skeletal Class III during the peak growth periods and later. Cervical inclination variables were greater in skeletal Class III than in skeletal Class II. Variables of craniofacial morphology and craniocervical posture are more correlated during the pubertal growth period and later in patients with sagittal skeletal malocclusion. A tendency is an indication of the close interrelationship that a more extended head was in skeletal Class II while a flexed head was in skeletal Class III. Nevertheless, with the considerations of some limitations involved in this study, further longitudinal studies with large samples are required to elucidate the relationship clearly.

Use of problem-based learning in orthopaedics education: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Currently, problem-based learning (PBL) has been widely used in many disciplines, but no systematic review has explored the advantages and disadvantages of PBL in orthopaedics education. METHODS: We searched the PubMed, Cochrane Library, Embase, Web of Science, Scopus, Chongqing VIP Database (VIP), Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases up to April 2023 to identify for relevant studies. Relevant studies were identified by using specific eligibility criteria, and data were extracted. RESULTS: A total of 51 randomized controlled trials with 4268 patients were included. Compared with traditional education, PBL teaching yielded significantly higher knowledge scores (SMD=1.10, 95% CI: 0.78~1.41, P<0.00001), procedural skill scores and clinical skill scores than traditional teaching (SMD=2.07, 95% CI: 1.61~2.53, P<0.00001; SMD=1.20, 95% CI: 0.88~1.52, P<0.00001). Moreover, the total scores were higher in the PBL teaching group than in the traditional teaching group (MD=5.69, 95% CI: 5.11~6.26, P<0.00001). Students also expressed higher levels of interest and satisfaction in the PBL teaching group than in the traditional teaching group (OR=4.70, 95% CI: 3.20~6.93, P<0.00001; OR=5.43, 95% CI: 3.83~7.69, P<0.00001). However, there was less learning time and higher levels of learning pressure in the PBL teaching group (OR=0.12, 95% CI: 0.06~0.24, P<0.00001; OR=5.95, 95% CI: 3.16~11.23, P<0.00001). CONCLUSION: Current evidence indicates that PBL teaching can increase knowledge scores, procedural skill scores, and clinical skill scores. Students have higher levels of interest in teaching and higher levels of teaching satisfaction in the PBL group. However, students can feel higher levels of study pressure and experience less study time. The findings of the current study need to be further verified in multicentre, double-blind and large-sample RCTs.

Integrated analyses revealed the potential role and immune link of mitochondrial dysfunction between periodontitis and type 2 diabetes mellitus.

There is a reciprocal comorbid relationship between periodontitis and type 2 diabetes mellitus (T2DM). Recent studies have suggested that mitochondrial dysfunction (MD) could be the key driver underlying this comorbidity. The aim of this study is to provide novel understandings into the potential molecular mechanisms between MD and the comorbidity, and identify potential therapeutic targets for personalized clinical management. MD-related differentially expressed genes (MDDEGs) were identified. Enrichment analyses and PPI network analysis were then conducted. Six algorithms were used to explore the hub MDDEGs, and these were validated by ROC analysis and qRT-PCR. Co-expression and potential drug targeting analyses were then performed. Potential biomarkers were identified using LASSO regression. The immunocyte infiltration levels in periodontitis and T2DM were evaluated via CIBERSORTx and validated in mouse models. Subsequently, MD-related immune-related genes (MDIRGs) were screened by WGCNA. The in vitro experiment verified that MD was closely associated with this comorbidity. GO and KEGG analyses demonstrated that the connection between periodontitis and T2DM was mainly enriched in immuno-inflammatory pathways. In total, 116 MDDEGs, eight hub MDDEGs, and two biomarkers were identified. qRT-PCR revealed a distinct hub MDDEG expression pattern in the comorbidity group. Altered immunocytes in disease samples were identified, and their correlations were explored. The in vivo examination revealed higher infiltration levels of inflammatory immunocytes. The findings of this study provide insight into the mechanism underlying the gene-mitochondria-immunocyte network and provide a novel reference for future research into the function of mitochondria in periodontitis and T2DM.

An Automatic Grading System for Orthodontically Induced External Root Resorption Based on Deep Convolutional Neural Network.

Orthodontically induced external root resorption (OIERR) is a common complication of orthodontic treatments. Accurate OIERR grading is crucial for clinical intervention. This study aimed to evaluate six deep convolutional neural networks (CNNs) for performing OIERR grading on tooth slices to construct an automatic grading system for OIERR. A total of 2146 tooth slices of different OIERR grades were collected and preprocessed. Six pre-trained CNNs (EfficientNet-B1, EfficientNet-B2, EfficientNet-B3, EfficientNet-B4, EfficientNet-B5, and MobileNet-V3) were trained and validated on the pre-processed images based on four different cross-validation methods. The performances of the CNNs on a test set were evaluated and compared with those of orthodontists. The gradient-weighted class activation mapping (Grad-CAM) technique was used to explore the area of maximum impact on the model decisions in the tooth slices. The six CNN models performed remarkably well in OIERR grading, with a mean accuracy of 0.92, surpassing that of the orthodontists (mean accuracy of 0.82). EfficientNet-B4 trained with fivefold cross-validation emerged as the final OIERR grading system, with a high accuracy of 0.94. Grad-CAM revealed that the apical region had the greatest effect on the OIERR grading system. The six CNNs demonstrated excellent OIERR grading and outperformed orthodontists. The proposed OIERR grading system holds potential as a reliable diagnostic support for orthodontists in clinical practice.

Recent advances in the mechanism of hydrogen sulfide in wound healing in diabetes.

Wound healing difficulties in diabetes continue to be a clinical challenge, posing a considerable burden to patients and society. Recently, exploration of the mechanism of wound healing and associated treatment options in diabetes has become topical. Of note, the positive role of hydrogen sulfide in promoting wound healing has been demonstrated in recent studies. Hydrogen sulfide is a confirmed gas transmitter in mammals, playing an essential role in pathology and physiology. This review describes the mechanism underlying the role of hydrogen sulfide in the promotion of diabetic wound healing and the potential for hydrogen sulfide supplementation as a therapeutic application.

Evaluation of MV140 in preventing recurrent urinary tract infections: a multicentre double-blind randomized controlled trial protocol.

OBJECTIVES: To determine, firstly, whether MV140 reduces rates of recurrent urinary tract infections (rUTIs) in patients older than 65 years, measured as the number of urinary tract infections (UTIs) detected over 12 months following the completion of a 3-month treatment course and, additionally, to assess the number of re-admissions to the emergency department, the rate of antibiotic use for UTIs, the safety profile of MV140, and quality of life. MATERIALS AND METHODS: This is a multicentre, double-blind, randomized controlled trial with two arms. Patients will be randomized and allocated to receive either a 3-month course of MV140 or placebo (two sublingual sprays daily). Participants will have 3-monthly consultations with the investigator for 12 months to assess differences in rates of rUTIs between the two groups. Study candidates will be identified and recruited from inpatient and outpatient clinics across Sydney via referral to the investigation team. After obtaining consent, participants will undergo initial study consultations including urine microscopy and culture, uroflowmetry, and bladder scan to assess postvoid residual urine volume. Participants will be randomized and provided with a unique trial number. Electronic medical records will be reviewed to collect relevant information. Participants will be provided with a study diary to record relevant data. RESULTS: Follow-up consultations will be conducted every 3 months for a 12-month duration, during which the study diary will be reviewed. These follow-up consultations will primarily occur via telephone review, however, there will be flexibility for in-person reviews for participants who find telephone consultation prohibitively difficult. CONCLUSION: This is a multicentre, double-blinded, randomised control trial, the first in Australia to assess the safety and efficacy of MV140 Uromune vaccine in prevention of recurrent UTIs. Results have been promissing in the global literatures.

A Chance Finding of High Grade Prostate Cancer in a 35-Year-Old Male - A Case Report and Outcomes of Robotic Radical Prostatectomy in Young Men with Prostate Cancer.

Background: Prostate cancer is often considered a disease of older men and this indeed fits with its peak incidence between 65-79 years of age. Reports of prostate cancer in men younger than 40 years of age and the outcomes of this age group following treatment are few in the literature. Here, we present the case of an unusual diagnosis of high grade prostate cancer in a very young man and outline early outcomes following treatment with robotic-assisted radical prostatectomy. Case Presentation: A 35-year-old male, intermittently taking finasteride for hair loss, was found to have an elevated prostate-specific antigen (PSA) of 12.5ng/mL leading to an incidental diagnosis of high grade prostate cancer. Targeted trans-perineal prostate biopsy found Gleason 4+5=9 acinar adenocarcinoma, without cribriform architecture but with features suspicious for extracapsular extension. Robotic radical prostatectomy with bilateral pelvic lymph node dissection was performed and found Gleason 4+5=9 adenocarcinoma with focal cribriform architecture, extra prostatic extension and clear margins, stage pT3a N0 M0. PSA was undetectable at 12 months, continence was immediate, and the patient reported strong erections soon after surgery. Family history of prostate cancer and genetic testing were both negative. Conclusion: This case highlights that not all clinically significant cancers will be identified by following PSA screening guidelines starting at 50 years of age (or 40 years of age for men with a family history of prostate cancer). While high grade prostate cancer in a man less than 40 years of age is uncommon, the literature suggests the incidence is increasing. Our case alongside series in the literature indicate that these men have better functional outcomes and equal oncological outcomes with early surgical intervention for localized disease when compared to the older population.

Segmental testicular infarction secondary to protein C deficiency.

Protein C deficiency is a rare blood disorder that increases the risk of thromboembolism, resulting in deep vein thrombosis, pulmonary embolisms and strokes. Segmental testicular infarction is also a rare condition with unclear aetiology. This case presents a man in his 50s with protein C deficiency who developed a segmental testicular infarction. The patient was managed conservatively, without surgical intervention. He was monitored with serial ultrasound, which demonstrated progression from normal testis to segmental infarction and eventually resolution. The case highlights that protein C deficiency can cause testicular infarction, and a multidisciplinary approach can help avoid unnecessary surgery with excellent outcomes. Segmental infarction should be considered in patients with pre-existing thrombophilias after excluding malignancy and infection. Conservative management with repeat ultrasonography and follow-up can be appropriate in such cases.

Urology case report - Emergency penectomy for the transfeminine patient.

Management of gender dysphoria and healthcare for transgender and non-binary patients is a growing field in Australia and abroad. Currently, gender-affirming surgery is not offered under Australia's national public health insurance. We present an unusual case of emergency penectomy required for a 57-year-old woman assigned-male-at-birth from rural Australia after a self-inflicted chemical burn. This case report outlines the surgical challenges of partial penectomy and neo meatus formation to allow for future gender-affirming surgery and highlights the lack of infrastructure within the public healthcare system for management of gender dysphoria both in rural and metropolitan settings.

Portable Handheld "SkinPen" Loaded with Biomaterial Ink for In Situ Wound Healing.

In situ bioprinting has emerged as an attractive tool for directly depositing therapy ink at the defective area to adapt to the irregular wound shape. However, traditional bioprinting exhibits an obvious limitation in terms of an unsatisfactory bioadhesive effect. Here, a portable handheld bioprinter loaded with biomaterial ink is designed and named "SkinPen". Gelatin methacrylate (GelMA) and Cu-containing bioactive glass nanoparticles (Cu-BGn) serve as the main components to form the hydrogel ink, which displays excellent biocompatibility and antibacterial and angiogenic properties. More importantly, by introducing ultrasound and ultraviolet in a sequential programmed manner, the SkinPen achieves in situ instant gelation and amplified (more than threefold) bioadhesive shear strength. It is suggested that ultrasound-induced cavitation and the resulting topological entanglement contribute to the enhanced bioadhesive performance together. Combining the ultrasound-enhanced bioadhesion with the curative role of the hydrogel, the SkinPen shows a satisfactory wound-healing effect in diabetic rats. Given the detachable property of the SkinPen, the whole device can be put in a first-aid kit. Therefore, the application scenarios can be expanded to many kinds of accidents. Overall, this work presents a portable handheld SkinPen that might provide a facile but effective approach for clinical wound management.

Low-Intensity Pulsed Ultrasound Attenuates Periodontal Ligament Cells Apoptosis by Activating Yes-Associated Protein-Regulated Autophagy.

OBJECTIVE: The goal of the work described here was to determine if low-intensity pulsed ultrasound (LIPUS) has an anti-inflammatory effect on lipopolysaccharide (LPS)-induced inflammation in periodontal ligament cells (PDLCs). The mechanism underlying this effect remains to be explored and is likely related to PDLC apoptosis regulated by Yes-associated protein (YAP) and autophagy. METHODS: To verify this hypothesis, we used a rat model of periodontitis and primary human PDLCs. We examined alveolar bone resorption in rats and apoptosis, autophagy and YAP activity in LPS-treated PDLCs with and without application of LIPUS by cellular immunofluorescence, transmission electron microscopy and Western blotting. Then, siRNA transfection was used to decrease YAP expression to confirm the regulatory role of YAP in the anti-apoptotic effect of LIPUS on PDLCs. DISCUSSION: We found that LIPUS attenuated alveolar bone resorption in rats and this was accompanied by YAP activation. LIPUS inhibited hPDLC apoptosis by YAP activation, and promoted autophagic degradation to help autophagy completion. These effects were reversed after YAP expression was blocked. CONCLUSION: LIPUS attenuates PDLC apoptosis by activating Yes-associated protein-regulated autophagy.

A survival nomogram model constructed with common clinical characteristics to assist clinical decisions for diffuse low-grade gliomas: A population analysis based on SEER database.

Background: The prognosis of diffuse low-grade gliomas (DLGGs, WHO grade 2) is highly variable, making it difficult to evaluate individual patient outcomes. In this study, we used common clinical characteristics to construct a predictive model with multiple indicators. Methods: We identified 2459 patients diagnosed with astrocytoma and oligodendroglioma from 2000 to 2018 in the SEER database. After removing invalid information, we randomly divided the cleaned patient data into training and validation groups. We performed univariate and multivariate Cox regression analyses and constructed a nomogram. Receiver operating characteristic (ROC) curve, c-index, calibration curve, and subgroup analyses were used to assess the accuracy of the nomogram by internal and external validation. Results: After univariate and multivariate Cox regression analyses, we identified seven independent prognostic factors, namely, age (P<0.001), sex (P<0.05), histological type (P<0.001), surgery (P<0.01), radiotherapy (P<0.001), chemotherapy (P<0.05) and tumor size (P<0.001). The ROC curve, c-index, calibration curve, and subgroup analyses of the training group and the validation group showed that the model had good predictive value. The nomogram for DLGGs predicted patients' 3-, 5- and 10-year survival rates based on these seven variables. Conclusions: The nomogram constructed with common clinical characteristics has good prognostic value for patients with DLGGs and can help physicians make clinical decisions.

Time-series expression profiles of mRNAs and lncRNAs during mammalian palatogenesis.

OBJECTIVES: Mammalian palatogenesis is a highly regulated morphogenetic process to form the intact roof of the oral cavity. Long noncoding RNAs (lncRNAs) and mRNAs participate in numerous biological and pathological processes, but their roles in palatal development and causing orofacial clefts (OFC) remain to be clarified. METHODS: Palatal tissues were separated from ICR mouse embryos at four stages (E10.5, E13.5, E15, and E17). Then, RNA sequencing (RNA-seq) was used. Various analyses were performed to explore the results. Finally, hub genes were validated via qPCR and in situ hybridization. RESULTS: Starting from E10.5, the expression of cell adhesion genes escalated in the following stages. Cilium assembly and ossification genes were both upregulated at E15 compared with E13.5. Besides, the expression of cilium assembly genes was also increased at E17 compared with E15. Expression patterns of three lncRNAs (H19, Malat1, and Miat) and four mRNAs (Cdh1, Irf6, Grhl3, Efnb1) detected in RNA-seq were validated. CONCLUSIONS: This study provides a time-series expression landscape of mRNAs and lncRNAs during palatogenesis, which highlights the importance of processes such as cell adhesion and ossification. Our results will facilitate a deeper understanding of the complexity of gene expression and regulation during palatogenesis.

A Biomimetic Smart Nanoplatform as "Inflammation Scavenger" for Regenerative Therapy of Periodontal Tissue.

Introduction: The functional reconstruction of periodontal tissue defects remains a clinical challenge due to excessive and prolonged host response to various endogenous and exogenous pro-inflammatory stimuli. Thus, a biomimetic nanoplatform with the capability of modulating inflammatory response in a microenvironment-responsive manner is attractive for regenerative therapy of periodontal tissue. Methods: Herein, a facile and green design of engineered bone graft materials was developed by integrating a biomimetic apatite nanocomposite with a smart-release coating, which could realize inflammatory modulation by "on-demand" delivery of the anti-inflammatory agent through a pH-sensing mechanism. Results: In vitro and in vivo experiments demonstrated that this biocompatible nanoplatform could facilitate the clearance of reactive oxygen species in human periodontal ligament stem cells under inflammatory conditions via inhibiting the production of endogenous proinflammatory mediators, in turn contributing to the enhanced healing efficacy of periodontal tissue. Moreover, this system exhibited effective antimicrobial activity against common pathogenic bacteria in the oral cavity, which is beneficial for the elimination of exogenous pro-inflammatory factors from bacterial infection during healing of periodontal tissue. Conclusion: The proposed strategy provides a versatile apatite nanocomposite as a promising "inflammation scavenger" and propels the development of intelligent bone graft materials for periodontal and orthopedic applications.

Does head and cervical posture correlate to malocclusion? A systematic review and meta-analysis.

BACKGROUND: The association of head and cervical posture with malocclusion has been studied for many years. Despite extensively encouraging researches, no conclusive evidence has been reached for clinical application. OBJECTIVE: To identify the question "Does head and cervical posture correlate to malocclusion?", a systematic review and meta-analysis based on the available studies were carried out (PROSPERO registration number: CRD42022319742). METHODS: A search of PubMed, Embase, Cochrane Library, and the grey literature was performed without language restrictions. The study screening, data extraction, risk-of-bias evaluation and methodological quality assessment were performed by two independent investigators. When a disagreement arose, a third author was consulted. RESULTS: 6 original cross-sectional studies involving 505 participants were included, which were of moderate methodological quality. NL/VER in Class Ⅱ group and NL/CVT in Class Ⅲ group showed significant differences compared to Class Ⅰ group, but no significant differences were observed in most of the variables like NSL/VER, OPT/CVT, OPT/HOR, CVT/HOR, NSL/OPT, NSL/CVT, NL/OPT in Class Ⅱ and Ⅲ groups. CONCLUSIONS: The results suggested that the current research evidence is not sound enough to prove the association of head and cervical posture with sagittal malocclusion. Better controlled design and a larger sample size are required for clarifying this question in future study.

Nanocarrier-Assisted Delivery of Metformin Boosts Remodeling of Diabetic Periodontal Tissue via Cellular Exocytosis-Mediated Regulation of Endoplasmic Reticulum Homeostasis.

Endoplasmic reticulum (ER) dysfunction is a potential contributor to the impaired repair capacity of periodontal tissue in diabetes mellitus (DM) patients. Restoring ER homeostasis is thus critical for successful regenerative therapy of diabetic periodontal tissue. Recent studies have shown that metformin can modulate DM-induced ER dysfunction, yet its mechanism remains unclear. Herein, we show that high glucose elevates the intracellular miR-129-3p level due to exocytosis-mediated release failure and subsequently perturbs ER calcium homeostasis via downregulating transmembrane and coiled-coil domain 1 (TMCO1), an ER Ca2+ leak channel, in periodontal ligament stem cells (PDLSCs). This results in the degradation of RUNX2 via the ubiquitination-dependent pathway, in turn leading to impaired PDLSCs osteogenesis. Interestingly, metformin could upregulate P2X7R-mediated exosome release and decrease intracellular miR-129-3p accumulation, which restores ER homeostasis and thereby rescues the impaired PDLSCs. To further demonstrate the in vivo effect of metformin, a nanocarrier for sustained local delivery of metformin (Met@HALL) in periodontal tissue is developed. Our results demonstrate that compared to controls, Met@HALL with enhanced cytocompatibility and pro-osteogenic activity could boost the remodeling of diabetic periodontal tissue in rats. Collectively, our findings unravel a mechanism of metformin in restoring cellular ER homeostasis, enabling the development of a nanocarrier-mediated ER targeting strategy for remodeling diabetic periodontal tissue.

Low-intensity pulsed ultrasound promotes periodontal regeneration in a beagle model of furcation involvement.

Objective: To evaluate the regeneration potential of periodontitis tissue treated by low-intensity pulsed ultrasound (LIPUS) combined with the guided tissue regeneration (GTR) technique in a beagle model of furcation involvement (FI). Background: Achieving predictable regeneration remains a clinical challenge for periodontitis tissue due to the compromised regenerative potential caused by chronic inflammation stimulation. LIPUS, an FDA-approved therapy for long bone fracture and non-unions, has been demonstrated effective in the in vitro attenuation of inflammation-induced dysfunction of periodontal ligament stem cells (PDLSCs), the key cells contributing to periodontal regeneration. However, the in vivo effect of LIPUS on periodontitis tissue is rarely reported. Methods: A beagle model of FI was established, and the experimental teeth were randomly assigned into three groups: control group, GTR group, and GTR+LIPUS group. Radiographic examinations were performed, and clinical periodontal parameters were recorded to reflect the periodontal condition of different groups. Histological analyses using H&E and Masson's staining were conducted to evaluate the periodontal tissue regeneration. Results: LIPUS could enhance new periodontal bone formation and bone matrix maturity in FI after GTR treatment. Moreover, clinical assessment and histomorphometric analyses revealed less inflammatory infiltration and superior vascularization within bone grafts in the LIPUS treatment group, indicating the anti-inflammatory and pro-angiogenic effects of LIPUS in FI. Conclusion: Our investigation on a large animal model demonstrated that LIPUS is a promising adjunctive approach for the regeneration of periodontitis tissue, paving a new avenue for LIPUS application in the field of periodontal regenerative medicine.

MicroRNA-29b/graphene oxide-polyethyleneglycol-polyethylenimine complex incorporated within chitosan hydrogel promotes osteogenesis.

MicroRNAs (miRNAs) play a pivotal role in regulating a number of physiologic and pathologic processes including bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, making them a candidate used to promote osteogenesis. However, due to intrinsic structure and characteristics, "naked" miRNAs are unstable in serum and could not pass across the cellular membrane. Nano delivery systems seem to be a solution to these issues. Recently, graphene oxide (GO)-based nanomaterials are considered to be promising for gene delivery due to their unique physiochemical characteristics such as high surface area, biocompatibility, and easy modification. In this work, a GO-based nanocomplex functionalized by polyethyleneglycol (PEG) and polyethylenimine (PEI) was prepared for loading and delivering miR-29b, which participates in multiple steps of bone formation. The nanocomplex revealed good biocompatibility, miRNA loading capacity, and transfection efficiency. The miR-29b/GO-PEG-PEI nanocomplex was capsulated into chitosan (CS) hydrogel for osteogenesis. In vitro and in vivo evaluation indicated that miR-29b/GO-PEG-PEI@CS composite hydrogel was able to promote BMSC osteogenic differentiation and bone regeneration. All these results indicate that PEG/PEI functionalized GO could serve as a promising candidate for miRNA cellular delivery, and the miR-29b/GO-PEG-PEI@CS hydrogel has the potential for repairing bone defects in vivo.