Nanotube topography rejuvenates the senescence of mesenchymal stem cells by activating YAP signalling.

Improving the regenerative ability of senescent stem cells is a critical issue in combating aging. The destiny and function of senescent stem cells are controlled by the niche, including the physical architecture of the surface of the extracellular matrix (ECM). In this study, we explored the functions of TiO2 nanotube topography on mesenchymal stem cells (MSCs) under senescence, as well as its mechanical effects on senescence. First, we created different nanotube topographies on the titanium samples. Next, we cultured senescent mesenchymal stem cells (S-MSCs) on samples with various nanotube topographies to determine suitable parameters. We found nanotube with a diameter of 10 nm significantly alleviated the cellular senescence of S-MSCs and improved the osteogenic differentiation of S-MSCs in vitro. Using an ectopic periodontium regeneration model, we confirmed that specific nanotube topography could promote tissue regeneration of S-MSCs in vivo. Moreover, we demonstrated that nanotube topography activated YAP in S-MSCs and reformed nuclear-cytoskeletal morphology to inhibit senescence. Taken together, our study establishes a bridge linking between nano-topography, mechanics, and senescence, suggesting a potential strategy to improve tissue regeneration in aged individuals by providing optimized surface topography on biomaterials.

Functional diversity of apoptotic vesicle subpopulations from bone marrow mesenchymal stem cells in tissue regeneration.

Apoptosis releases numerous apoptotic vesicles that regulate processes such as cell proliferation, immunity, and tissue regeneration and repair. Now, it has also emerged as an attractive candidate for biotherapeutics. However, apoptotic vesicles encompass a diverse range of subtypes, and it remains unclear which specific subtypes play a pivotal role. In this study, we successfully isolated different apoptotic vesicle subtypes based on their sizes and characterized them using NTA and TEM techniques, respectively. We compared the functional variances among the distinct subtypes of apoptotic vesicles in terms of stem cell proliferation, migration, and differentiation, as well as for endothelial cell and macrophage function, effectively identifying subtypes that exhibit discernible functional differences. ApoSEV (with diameter <1000 nm) promoted stem cell proliferation, migration, and multi-potent differentiation, and accelerated skin wound healing of diabetes mouse model, while apoBD (with diameter >1000 nm) played the opposite effect on cell function and tissue regeneration. Lastly, employing protein analysis and gene sequencing techniques, we elucidated the intrinsic mechanisms underlying these differences between different subtypes of apoEVs. Collectively, this study identified that apoptotic vesicle subtypes possessed distinct bio-functions in regulating stem cell function and behaviour and modulating tissue regeneration, which primarily attribute to the distinct profiling of protein and mRNA in different subtypes. This comprehensive analysis of specific subtypes of apoEVs would provide novel insights for potential therapeutic applications in cell biology and tissue regeneration.

ApoSEVs-Mediated Modulation of Versatile Target Cells Promotes Diabetic Wound Healing: Unveiling a Promising Strategy.

Background: Diabetic chronic wounds present a formidable challenge in clinical management, lacking effective treatment options. Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for tissue repair and regeneration. However, transplanted MSCs often undergo rapid apoptosis, giving rise to heterogeneous extracellular vesicles (EVs), including apoptotic bodies (apoBDs) and apoptotic small extracellular vesicles (apoSEVs). The potential stimulatory role of these EVs in diabetic wound healing remains unknown. Methods: In this study, we investigated the effects of apoSEVs derived from adipose-derived mesenchymal/stromal cells (ADSCs) on the recovery of diabetic wounds by modulating the function of versatile target cells. First, we characterized the apoSEVs and apoBDs derived from apoptotic ADSCs. Subsequently, we evaluated the effects of apoSEVs and apoBDs on macrophages, endothelial cells, and fibroblasts, three essential cell types in wound healing, under high-glucose conditions. Furthermore, we developed a gelatin methacryloyl (GelMA) hydrogel for the sustained release of apoSEVs and investigated its therapeutic effects on wound healing in type 2 diabetic mice in vivo. Results: apoSEVs facilitated the polarization of M1 phenotype macrophages to M2 phenotype, promoted proliferation, migration, and tube formation of endothelial cells, and enhanced fibroblast proliferation and migration. However, apoBDs failed to improve the function of endothelial cells and fibroblasts. In vivo, the apoSEVs-loaded GelMA effectively promoted wound healing by facilitating collagen fiber deposition, angiogenesis, and immune regulation. Conclusion: Our study elucidates the beneficial effects of apoSEVs on wound recovery in diabetes and introduces a novel strategy for diabetic wound treatment based on apoSEVs.

Effect of Age on Transalveolar Sinus Floor Elevation with Simultaneous Placement of Dental Implants: A Retrospective Study.

Purpose: To analyze the effects of age on the sinus graft remodeling of transalveolar sinus floor elevation (SFE) with simultaneous placement of dental implants. Materials and Methods: A retrospective study design was adopted. A total of 222 sites in 216 patients who underwent transalveolar SFE with immediate implant placement were included. The clinical and radiographic data were collected at preoperative, postoperative, and postloading time points. Age was divided into three groups: < 30 years, 30 to 50 years, and > 50 years. The ratio of sinus graft resorption (Ratio) was used to evaluate the outcomes of the surgery and loading. ANOVA was applied to explore the correlation of total elevation height (TEH) with implant loading. The Ridge regression model was used to explore the relationship between Ratio and age and other possible factors. Results: A total of 222 implants in 216 patients were included for implant-based analysis. The TEH averaged 6.983 ± 2.251 mm on the day after surgery (T1), and sinus graft resorption was found during the healing period and after implant loading (P < .01). Age was found to be a reliable correlation with the Ratio (P < .01). A significantly decreased bone formation efficiency was found with aging. Conclusion: According to the results of this retrospective chart review, age was the main factor affecting the outcomes when applying transalveolar SFE with simultaneous implant placement. This finding could be a guide for clinical treatment.

Vascularized dental pulp regeneration using cell-laden microfiber aggregates.

Regeneration of dental pulp via the transplantation of dental pulp stem cells (DPSCs) has emerged as a novel therapy for dental pulp necrosis after inflammation and injury. However, providing sufficient oxygen and nutrients to support stem cell survival, self-renewal, and differentiation in the narrow root canal remains a great challenge. In this study, we explored a novel strategy based on cell-laden microfibers for dental pulp regeneration. Firstly, we fabricated suitable GelMA hydrogels that facilitate the survival and proliferation of DPSCs and human umbilical vein endothelial cells (HUVECs) and possess satisfactory biomechanical properties to generate microfibers. Two kinds of GelMA microfibers were fabricated with DPSCs and HUVECs via a silicone-tube-based coagulant bath-free method. Live/dead and Ki-67 immunofluorescence staining assays identified that these two cell lines maintained high survival rate and proliferation ability in GelMA microfibers. Immunofluorescence staining confirmed that DPSCs fully spread in the microfibers and highly expressed CD90 and laminin. HUVECs positively express CD31 and VE-cad in microfibers and could migrate well in the GelMA hydrogel. In vitro permeation experiments confirmed the superiority of microfiber aggregates (MAs) in liquid permeation compared to GelMA hydrogel blocks. We further adopted an ectopic pulp regeneration assay in nude mice to validate the regeneration of the aggregates of mixed DPSC-microfibers and HUVEC-microfibers in vivo. Compared to a conventional mixture of DPSCs and HUVECs in GelMA hydrogel blocks, the aggregates of cell-laden microfibers generated more pulp-like tissue, blood vessels, and odontoblast-like cells that positively express DMP-1 and DSPP. To our knowledge, this is the first attempt to apply cell-laden MAs for pulp regeneration. Our study proposes a new solution to the challenge of pulp regeneration, which might promote the clinical translation and application of stem cell-based therapy.

Surgical Navigation System for Hypertensive Intracerebral Hemorrhage Based on Mixed Reality.

Hypertensive intracerebral hemorrhage (HICH) is an intracerebral bleeding disease that affects 2.5 per 10,000 people worldwide each year. An effective way to cure this disease is puncture through the dura with a brain puncture drill and tube; the accuracy of the insertion determines the quality of the surgery. In recent decades, surgical navigation systems have been widely used to improve the accuracy of surgery and minimize risks. Augmented reality- and mixed reality-based surgical navigation is a promising new technology for surgical navigation in the clinic, aiming to improve the safety and accuracy of the operation. In this study, we present a novel multimodel mixed reality navigation system for HICH surgery in which medical images and virtual anatomical structures can be aligned intraoperatively with the actual structures of the patient in a head-mounted device and adjusted when the patient moves in real time while under local anesthesia; this approach can help the surgeon intuitively perform intraoperative navigation. A novel registration method is used to register the holographic space and serves as an intraoperative optical tracker, and a method for calibrating the HICH surgical tools is used to track the tools in real time. The results of phantom experiments revealed a mean registration error of 1.03 mm and an average time consumption of 12.9 min. In clinical usage, the registration error was 1.94 mm, and the time consumption was 14.2 min, showing that this system is sufficiently accurate and effective for clinical application.

Personalized virtual reality simulation training system for percutaneous needle insertion and comparison of zSpace and vive.

PURPOSE: In this research, we present a personalized simulation training system for percutaneous needle insertion based on virtual reality (VR). Within this system, surgeons can become more familiar with real surgical procedures, thereby reducing errors that may occur in real surgery. Additionally, different VR technologies, i.e., zSpace and Vive, were compared to provide surgeons with a better surgical training environment. METHODS: and Methods A VR system combined with the treatment planning system was developed to create personalized patient training environment. An evaluation study recruiting twenty novices was performed to demonstrate the system. Each participant performed six independent needle placements using the VR system. Placement time was recorded. Placement error was defined as the distance from the needle tip to the target center. The participants completed a seven-point Likert scale questionnaire after the simulation. RESULTS: Compared with Vive, using zspace reduces the placement time (from 90.32 s to 68.94 s). The placement error using zSpace and Vive was similar (1.27 ± 0.68 mm, 1.56 ± 0.81 mm, respectively). The questionnaire survey results show that most participants are highly satisfied with the training effect of the VR system. Participants prefer the operation mode and convenience of zSpace but think that the immersion of Vive is better. CONCLUSIONS: The personalized virtual reality surgical training system was effective as a training system for percutaneous needle insertion. The system based on zSpace had a shorter placement time while maintaining placement accuracy compared to the system based on Vive. The system based on zSpace achieved higher satisfaction in most aspects except for immersion.

Augmented reality surgical navigation system based on the spatial drift compensation method for glioma resection surgery.

BACKGROUND: The number of patients who suffer from glioma has been increasing, and this malignancy is a serious threat to human health. The mainstream treatment for glioma is surgical resection; therefore, accurate resection can improve postoperative patient recovery. PURPOSE: Many studies have investigated surgical navigation guided by mixed reality, with good outcomes. However, the limitations of mixed reality, such as spatial drift caused by environmental changes, limit its clinical application. Therefore, we present a mixed reality surgical navigation system for glioma resection. Preoperative information can be fused precisely with the real patient with the spatial compensation method to achieve clinically suitable accuracy. METHODS: A head-mounted device was used to display virtual information, and a markerless spatial registration method was applied to precisely align the virtual anatomy with the real patient preoperatively. High-accuracy preoperative and intraoperative movement and spatial drift compensation methods were used to increase the positional accuracy of the mixed reality-guided glioma resection system when the patient's head is fixed to the bed frame. Several experiments were designed to validate the accuracy and efficacy of this system. RESULTS: Phantom experiments were performed to test the efficacy and accuracy of this system under ideal conditions, and clinical tests were conducted to assess the performance of this system in clinical application. The accuracy of spatial registration was 1.18 mm in the phantom experiments and 1.86 mm in the clinical application. CONCLUSIONS: Herein, we present a mixed reality-based multimodality-fused surgical navigation system for assisting surgeons in intuitively identifying the glioma boundary intraoperatively. The experimental results indicate that this system has suitable accuracy and efficacy for clinical usage.

A neuroendoscopic navigation system based on dual-mode augmented reality for minimally invasive surgical treatment of hypertensive intracerebral hemorrhage.

BACKGROUND AND OBJECTIVE: Hypertensive intracerebral hemorrhage is characterized by a high rate of morbidity, mortality, disability and recurrence. Neuroendoscopy has been utilized for treatment as an advanced technology. However, traditional neuroendoscopy allows professionals to see only tissue surfaces, and the field of vision is limited, which cannot provide spatial guidance. In this study, an AR-based neuroendoscopic navigation system is proposed to assist surgeons in locating and clearing hematoma. METHODS: The neuroendoscope can be registered through the vector closed loop algorithm. The single-shot method is designed to register medical images with patients precisely. Real-time AR is realized based on video stream fusion. Dual-mode AR navigation is proposed to provide comprehensive guidance from catheter implantation to hematoma removal. A series of experiments is designed to validate the accuracy and significance of this system. RESULTS: The average root mean square error of the registration between medical images and patients is 0.784 mm, and the variance is 0.1426 mm. The pixel mismatching degrees are less than 1% in different AR modes. In catheter implantation experiments, the average error of distance is 1.28 mm, and the variance is 0.43 mm, while the average error of angles is 1.34°, and the variance is 0.45°. Comparative experiments are also conducted to evaluate the feasibility of this system. CONCLUSION: This system can provide stereo images with depth information fused with patients to guide surgeons to locate targets and remove hematoma. It has been validated to have high accuracy and feasibility.

Estrogen-Related Receptor γ Induces Angiogenesis and Extracellular Matrix Degradation of Temporomandibular Joint Osteoarthritis in Rats.

The main causes of cartilage destruction during temporomandibular joint osteoarthritis (TMJOA) are extracellular matrix degradation and angiogenesis, accompanied by an increased level of matrix-degrading enzymes and proangiogenic factors. Interleukin 6 and extracellular signal-regulated kinase (ERK) signaling pathways may play a critical role in these two processes simultaneously, but researchers have not clearly determined the mechanism. We hypothesized that estrogen-related receptor γ (ERRγ) is involved in both cartilage degeneration and angiogenesis in TMJOA. The interactions between ERRγ and the Mmp9 and Vegfa promoter regions were investigated using a chromatin immunoprecipitation (ChIP) assay. A chick embryo chorioallantoic membrane (CAM) assay was performed to investigate the inhibitory effects of U0126 and GSK5182 on angiogenesis. Western blotting, reverse transcription-quantitative PCR (RT-qPCR), immunofluorescence staining, toluidine blue staining, and transfection with cDNAs or small interfering RNAs (siRNAs) were performed on primary mandibular condylar chondrocytes (MCCs). Unilateral anterior crossbite-induced TMJOA models were established in rats, and Western blotting, RT-qPCR, immunohistochemistry, and Safranin O-Fast Green staining were performed to evaluate changes in vivo. ERK1/2 activated matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor A (VEGFA), which are involved in cartilage destruction, through ERRγ. Based on the ChIP assay results, ERRγ directly activated the transcription of the Mmp9 and Vegfa genes. In chick embryo CAM models, U0126 and GSK5182 significantly inhibited angiogenesis. In conclusion, ERRγ is a downstream transcription factor of ERK1/2, and its upregulation leads to extracellular matrix degradation and angiogenesis in TMJOA. This study identified a common factor between inflammation and vascularization in OA as well as a new therapeutic target for OA: ERRγ.

Efficacy of secondary closure technique after extraction of third molars: a meta-analysis.

The purpose of this study was to assess the influence of two suture methods on the postoperative complications of extraction of mandibular third molars (M3M). We searched the MEDLINE (PubMed), Cochrane Library, and Web of Science databases until 18 May 2018 for randomised controlled trials (RCT) that evaluated the influence of any suture techniques on postoperative complications after the removal of impacted M3M. Pain, facial swelling, and trismus were measured for both the early stage (2-3 days) and late stage (5-7 days) after extraction. We identified 655 records, of which five were assessed for eligibility. All trials included had a moderate risk of bias. The analysis showed that the patients whose wounds had been closed primarily had significantly more pain than those whose wounds were closed secondarily (a wedge of mucosa) during the early stage (standardised mean difference (SMD), -0.49; 95% CI -0.71 to -0.27; P<0.0001) and the late stage (SMD -0.36; 95% CI -0.54 to -0.19; P<0.0001) after the removal of impacted M3M. Patients whose wounds were closed secondarily had less swelling (mm) at the postoperative early stage (SMD -1.12; 95% CI -1.57 to -0.66; P<0.00001) and late stage (SMD -0.51; 95% CI -0.68 to -0.33; P<0.00001). There was more trismus in the primary closure group than in the secondary group during both stages. Our findings suggest that secondary closure causes less pain, facial swelling, and trismus in both early and late stages of surgical removal of impacted M3M, and therefore it improves the quality of life by reducing postoperative discomfort.

Anesthetic Efficiency of Articaine Versus Lidocaine in the Extraction of Lower Third Molars: A Meta-Analysis and Systematic Review.

PURPOSE: The purpose of this study was to evaluate whether the anesthetic efficiency of articaine is superior to that of lidocaine during lower third molar extraction (LTME). MATERIALS AND METHODS: Three electronic databases (PubMed, Cochrane, and Web of Science) were searched to identify randomized controlled trials up to December, 31 2017. Five evaluation indexes were extracted, namely success rate of anesthesia, subjective onset time of anesthesia, objective onset time of anesthesia, duration time of anesthesia, and intraoperative pain assessment, to assess the anesthesia efficiency of the 2 solutions. All data analyses were conducted using Review Manager (version 5.3; The Cochrane Collaboration, London, United Kingdom). RESULTS: Nine studies were included in this review. The sample was composed of 770 LTMEs from 493 patients, with 382 LTMEs in the lidocaine group and 388 LTMEs in the articaine group. Compared with lidocaine, 4% articaine with 1:100,000 epinephrine showed a higher success rate of anesthesia (risk ratio, 1.10; 95% confidence interval [CI], 1.01 to 1.21; P = .03), shorter subjective onset time of anesthesia (standardized mean difference, 1.20; 95% CI, 0.50 to 1.89; P = .0007), and longer duration time of anesthesia (mean difference, 0.83 hours; 95% CI, 0.59 to 1.07 hours; P < .00001); however, for intraoperative pain assessment (mean difference, 3.12 mm; 95% CI, -0.13 to 6.37 mm; P = .06) and objective onset time of anesthesia (standardized mean difference, 0.44; 95% CI, -0.39 to 1.26; P = .30), there was no significant difference between the 2 solutions. CONCLUSIONS: The results of this study suggest that 4% articaine with 1:100,000 epinephrine possesses superior anesthetic efficiency relative to lidocaine for inferior alveolar nerve blocks during LTME.