UBE2C orchestrates bone formation through stabilization of SMAD1/5.

While previous studies have demonstrated the role of ubiquitin-conjugating enzyme 2C (UBE2C) in promoting ß-cell proliferation and cancer cell lineage expansion, its specific function and mechanism in bone marrow mesenchymal stem/stromal cells (BMSCs) growth and differentiation remain poorly understood. Our findings indicate that mice with conditional Ube2c deletions in BMSCs and osteoblasts exhibit reduced skeletal bone mass and impaired bone repair. A significant reduction in the proliferative capacity of BMSCs was observed in conditional Ube2c knockout mice, with no effect on apoptosis. Additionally, conditional Ube2c knockout mice exhibited enhanced osteoclastic activity and reduced osteogenic differentiation. Furthermore, human BMSCs with stable UBE2C knockdown exhibited diminished capacity for osteogenic differentiation. Mechanistically, we discovered that UBE2C binds to and stabilizes SMAD1/5 protein expression levels. Interestingly, UBE2C's role in regulating osteogenic differentiation and SMAD1/5 expression levels appears to be independent of its enzymatic activity. Notably, UBE2C regulates osteogenic differentiation through SMAD1/5 signaling. In conclusion, our findings underscore the pivotal role of UBE2C in bone formation, emphasizing its contribution to enhanced osteogenic differentiation through the stabilization of SMAD1/5. These results propose UBE2C as a promising target for BMSC-based bone regeneration.

Effects of Local Treatment in Combination with Systemic Therapy for Advanced Esophageal Cancer: A Systematic Review and Meta-analysis.

Purpose: Initial studies investigating the combination of local and systemic treatments in advanced esophageal cancer (EC) have conflicting conclusions regarding survival benefits. The objective of this systematic review and meta-analysis is to assess the efficacy of the addition of local therapy to systemic treatments in patients with advanced EC. Methods and Materials: A systematic literature search was conducted in the PubMed, EMBASE, and CENTRAL databases. Key eligibility criteria included studies that enrolled patients with histologically confirmed EC or esophagogastric junction cancer with metastasis or recurrence and compared survival benefits between the combined local and systemic treatment group and the systemic treatment alone group. Survival outcomes, represented by hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), were pooled using a random effects model. The MINORS score was adopted for quality assessment. Risk of bias was statistically examined by Begg's and Egger's tests. Results: A total of 1 randomized controlled trial (RCT) and 10 qualified retrospective studies including 14,489 patients were identified. Addition of local therapy to systemic treatment significantly improved PFS (HR, 0.52; 95% CI, 0.37-0.73; P < .001) and OS (HR, 0.69; 95% CI, 0.58-0.81; P < .0001) compared with systemic treatment alone. The subgroup analysis revealed that combined local and systemic treatment conferred a significant survival advantage in both patients with oligometastasis (PFS: HR, 0.45; 95% CI, 0.31-0.64; P < .0001; OS: HR, 0.62; 95% CI, 0.48-0.79; P < .0001) and recurrence (OS: HR, 0.55; 95% CI, 0.37-0.81; P = .002). Conclusions: In conclusion, addition of local treatment to systemic therapy can improve survival in patients with advanced EC, particularly in those with oligometastasis or recurrent diseases.

Preoperative CT-based radiomic prognostic index to predict the benefit of postoperative radiotherapy in patients with non-small cell lung cancer: a multicenter study.

BACKGROUND: The value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT. METHODS: Patients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI. RESULTS: In total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1-6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18-4.52), cohort 2 (HR = 1.64, 95% CI: 1.26-2.14), cohort 3 (HR = 2.53, 95% CI: 1.45-4.3), cohort 4 (HR = 1.24, 95% CI: 1.01-1.52), cohort 5 (HR = 2.56, 95% CI: 0.73-9.02), cohort 6 (HR = 2.30, 95% CI: 0.53-10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60-0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50-0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46-0.70), and RPI (C-index: 0.65, 95% CI: 0.54-0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40-0.91; p = 0.02), while patients in the low-risk and high-risk groups did not. CONCLUSIONS: We developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.

MRI-based vertebral bone quality score as a novel bone status marker of patients with adolescent idiopathic scoliosis.

To investigate the application of MRI-based vertebral bone quality (VBQ) score in assessing bone mineral density (BMD) for patients with adolescent idiopathic scoliosis (AIS). We reviewed the data of AIS patients between January 2021 and October 2023 with MRI, whole-spine plain radiographs, quantitative computed tomography (QCT) and general information. VBQ score was calculated using T1-weighted MRI. Univariate analysis was applied to present the differences between variables of patients with normal BMD group (QCT Z-score > - 2.0) and low BMD group (QCT Z-score ≤ - 2.0). The correlation between VBQ score and QCT Z-score was analyzed with Pearson correlation test. A multivariate logistic regression model was used to determine the independent factors related to low BMD. Receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic performance of VBQ score in distinguishing low BMD. A total of 136 AIS patients (mean age was 14.84 ± 2.10 years) were included, of which 41 had low BMD. The low BMD group had a significantly higher VBQ score than that in normal group (3.48 ± 0.85 vs. 2.62 ± 0.62, P < 0.001). The VBQ score was significantly negative correlated with QCT Z score (r = - 0.454, P < 0.001). On multivariate analysis, VBQ score was independently associated with low BMD (OR: 4.134, 95% CI 2.136-8.000, P < 0.001). The area under the ROC curve indicated that the diagnostic accuracy of the VBQ score for predicting low BMD was 81%. A sensitivity of 65.9% with a specificity of 88.4% could be achieved for distinguishing low BMD by setting the VBQ score cutoff as 3.18. The novel VBQ score was a promising tool in distinguishing low BMD in patients with AIS and could be useful as opportunistic assessment for screening and complementary evaluation to QCT before surgery.

Biomaterials science and surface engineering strategies for dental peri-implantitis management.

Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.

TGF-ß signaling regulates differentiation of MSCs in bone metabolism: disputes among viewpoints.

Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into cells of different lineages to form mesenchymal tissues, which are promising in regard to treatment for bone diseases. Their osteogenic differentiation is under the tight regulation of intrinsic and extrinsic factors. Transforming growth factor ß (TGF-ß) is an essential growth factor in bone metabolism, which regulates the differentiation of MSCs. However, published studies differ in their views on whether TGF-ß signaling regulates the osteogenic differentiation of MSCs positively or negatively. The controversial results have not been summarized systematically and the related explanations are required. Therefore, we reviewed the basics of TGF-ß signaling and summarized how each of three isoforms regulates osteogenic differentiation. Three isoforms of TGF-ß (TGF-ß1/ß2/ß3) play distinct roles in regulating osteogenic differentiation of MSCs. Additionally, other possible sources of conflicts are summarized here. Further understanding of TGF-ß signaling regulation in MSCs may lead to new applications to promote bone regeneration and improve therapies for bone diseases.

Apoptotic Vesicles Derived from Dental Pulp Stem Cells Promote Bone Formation through the ERK1/2 Signaling Pathway.

Osteoporosis is a common degenerative bone disease. The treatment of osteoporosis remains a clinical challenge in light of the increasing aging population. Human dental pulp stem cells (DPSCs), a type of mesenchymal stem cells (MSCs), are easy to obtain and have a high proliferation ability, playing an important role in the treatment of osteoporosis. However, MSCs undergo apoptosis within a short time when used in vivo; therefore, apoptotic vesicles (apoVs) have attracted increasing attention. Currently, the osteogenic effect of DPSC-derived apoVs is unknown; therefore, this study aimed to determine the role of DPSC-derived apoVs and their potential mechanisms in bone regeneration. We found that MSCs could take up DPSC-derived apoVs, which then promoted MSC osteogenesis in vitro. Moreover, apoVs could increase the trabecular bone count and bone mineral density in the mouse osteoporosis model and could promote bone formation in rat cranial defects in vivo. Mechanistically, apoVs promoted MSC osteogenesis by activating the extracellular regulated kinase (ERK)1/2 signaling pathway. Consequently, we propose a novel therapy comprising DPSC-derived apoVs, representing a promising approach to treat bone loss and bone defects.

Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake.

Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.

Mgp High-Expressing MSCs Orchestrate the Osteoimmune Microenvironment of Collagen/Nanohydroxyapatite-Mediated Bone Regeneration.

Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial-mediated bone regeneration, a comprehensive single-cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite-based bone repair materials via combining analysis of single-cell RNA sequencing and spatial transcriptomics. A group of functional MSCs with high expression of matrix Gla protein (Mgp) is identified, which may serve as a pioneer subpopulation involved in bone repair. Remarkably, these Mgp high-expressing MSCs (MgphiMSCs) exhibit efficient osteogenic differentiation potential and orchestrate the osteoimmune microenvironment around implanted biomaterials, rewiring the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand-receptor pair. The inhibition of Mdk/Lrp1 activates the pro-inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple immune-cell subsets also exhibit close crosstalk between MgphiMSCs via the secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles and interactions characterized in this study can broaden the understanding of the functional MSC subpopulations at the early stage of biomaterial-mediated bone regeneration and provide the basis for materials-designed strategies that target osteoimmune modulation.

Network analysis of histopathological image features and genomics data improving prognosis performance in clear cell renal cell carcinoma.

INTRODUCTION: Clear cell renal cell carcinoma is the most common type of kidney cancer, but the prediction of prognosis remains a challenge. METHODS: We collected whole-slide histopathological images, corresponding clinical and genetic information from the The Cancer Imaging Archive and The Cancer Genome Atlas databases and randomly divided patients into training (n = 197) and validation (n = 84) cohorts. After feature extraction by CellProfiler, we used 2 different machine learning techniques (Least Absolute Shrinkage and Selector Operation-regularized Cox and Support Vector Machine-Recursive Feature Elimination) and weighted gene co-expression network analysis to select prognosis-related image features and genes, respectively. These features and genes were integrated into a joint model using random forest and used to create a nomogram that combines other predictive indicators. RESULTS: A total of 4 overlapped features were identified, represented by the computed histopathological risk score in the random forest model, and showed predictive value for overall survival (test set: 1-year area under the curves (AUC) = 0.726, 3-year AUC = 0.727, and 5-year AUC = 0.764). The histopathological-genetic risk score (HGRS) integrating the genetic information computed performed better than the model that used image features only (test set: 1-year AUC = 0.682, 3-year AUC = 0.734, and 5-year AUC = 0.78). The nomogram (gender, stage, and HGRS) achieved the highest net benefit according to decision curve analysis compared to HGRS or clinical model. CONCLUSION: This study developed a histopathological-genetic-related nomogram by combining histopathological features and clinical predictors, providing a more comprehensive prognostic assessment for clear cell renal cell carcinoma patients.

Establishment of a 3D esthetic analysis workflow on 3D virtual patient and preliminary evaluation.

BACKGROUND: In esthetic dentistry, a thorough esthetic analysis holds significant role in both diagnosing diseases and designing treatment plans. This study established a 3D esthetic analysis workflow based on 3D facial and dental models, and aimed to provide an imperative foundation for the artificial intelligent 3D analysis in future esthetic dentistry. METHODS: The established 3D esthetic analysis workflow includes the following steps: 1) key point detection, 2) coordinate system redetermination and 3) esthetic parameter calculation. The accuracy and reproducibility of this established workflow were evaluated by a self-controlled experiment (n = 15) in which 2D esthetic analysis and direct measurement were taken as control. Measurement differences between 3D and 2D analysis were evaluated with paired t-tests. RESULTS: 3D esthetic analysis demonstrated high consistency and reliability (0.973 < ICC < 1.000). Compared with 2D measurements, the results from 3D esthetic measurements were closer to direct measurements regarding tooth-related esthetic parameters (P<0.05). CONCLUSIONS: The 3D esthetic analysis workflow established for 3D virtual patients demonstrated a high level of consistency and reliability, better than 2D measurements in the precision of tooth-related parameter analysis. These findings indicate a highly promising outlook for achieving an objective, precise, and efficient esthetic analysis in the future, which is expected to result in a more streamlined and user-friendly digital design process. This study was registered with the Ethics Committee of Peking University School of Stomatology in September 2021 with the registration number PKUSSIRB-202168136.

THE ACCURACY OF INTRAORAL SCAN IN OBTAINING DIGITAL IMPRESSIONS OF EDENTULOUS ARCHES: A SYSTEMATIC REVIEW.

OBJECTIVES: Accuracy is a crucial factor when assessing the quality of digital impressions. This systematic review aims to assess the accuracy of intraoral scan (IOS) in obtaining digital impressions of edentulous jaws. METHODS: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42022382983). A thorough retrieval of 7 electronic databases was undertaken, encompassing MEDLINE (PubMed), Web of Science, EMBASE, Scopus, Cochrane Library, Virtual Health Library, and Open gray, through September 11, 2023. A snowball search was performed by tracing the reference lists of the included studies. The Population, Intervention, Comparison, and Outcome (PICO) question of this systematic review was: "What is the accuracy of intraoral scan in obtaining digital impressions of edentulous arches?" The Modified Methodological Index for Nonrandomized Studies (MINORS) was employed to assess the risk of bias. RESULTS: Among the studies retrieved from databases and manual search, a total of 25 studies were selected for inclusion in this systematic review, including 9 in vivo and 16 in vitro studies. Twenty-one of the included studies utilized the 3D deviation analysis method, while 4 studies employed the linear or angular deviation analysis method. The accuracy results of in vitro studies indicated a trueness range of 20-600 µm and a precision range of 2-700 µm. Results of in vivo studies indicated a trueness range of 40-1380 µm, while the precision results were not reported. CONCLUSION: According to the results of this study, direct digital impressions by IOS cannot replace the conventional impressions of completely edentulous arches in vivo. Edentulous digital impressions by IOS demonstrated poor accuracy in peripheral areas with mobile tissues, such as the soft palate, vestibular sulcus, and sublingual area.

The Evaluation of Clinical and Intravoxel Incoherent Motion Parameters of Primary Lesion in Oligometastatic Prostate Cancer.

BACKGROUND: In the realm of cancer studies,the differences among the biological behavior of oligometastatic prostate cancer (OPCa), localized prostate cancer (LPCa), and widely prostate cancer (WPCa) are still unclear. OBJECTIVES: The purpose of our study was to assess the clinical and intravoxel incoherent motion (IVIM) parameters of tumor burden in OPCa. In addition, the correlation between clinical and IVIM parameters and the prostate-specific antigen nadir (PSAN) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) in OPCa was explored. It was found that the IVIM parameters could effectively differentiate LPCa and WPCa, as well as LPCa and OPC. Moreover, Gleason score (GS) was positively correlated with PSAN, while prostate volume was positively correlated with TTN. METHODS: About 54 patients were included in this retrospective study (mean age=74±7.4 years). ADC, D, D*, and f were acquired according to the biexponential Diffusion Weighted Imaging (DWI) model. The Kruskal-Wallis test was used to test the differences in clinical and IVIM parameters among the three groups. The Receiver Operating Characteristic (ROC) curve was used to evaluate the discrimination abilities. The Area Under the Curve (AUC) was compared using the DeLong test. Furthermore, Spearman correlation analysis was performed to assess the correlation between clinical and IVIM parameters of PSAN and TTN during initial ADT with OPCa. RESULTS: There were significant differences among the three groups observed for age, PSA, GS, ADC, D and D* values (P<0.05). Multi-parameter pairwise comparison results showed that significant differences between LPCa and WPCa were observed for the age, PSA, GS, ADC, D and D* values (P<0.05). However, D* was different between the LPCa and OPCa groups (P=0.032). GS showed a significant positive correlation with PSAN (Rho=0.594, P=0.042), and prostate volume showed a significant positive correlation with TTN (Rho=0.777, P=0.003). CONCLUSIONS: The IVIM parameters can effectively differentiate LPCa and WPCa, as well as LPCa and OPCa. Moreover, there was a certain trend in their distribution, which could reflect the tumor burden of PCa.

MR radiomics predicts pathological complete response of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a multicenter study.

BACKGROUND: More than 40% of patients with resectable esophageal squamous cell cancer (ESCC) achieve pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT), who have favorable prognosis and may benefit from an organ-preservation strategy. Our study aims to develop and validate a machine learning model based on MR radiomics to accurately predict the pCR of ESCC patients after nCRT. METHODS: In this retrospective multicenter study, eligible patients with ESCC who underwent baseline MR (T2-weighted imaging) and nCRT plus surgery were enrolled between September 2014 and September 2022 at institution 1 (training set) and between December 2017 and August 2021 at institution 2 (testing set). Models were constructed using machine learning algorithms based on clinical factors and MR radiomics to predict pCR after nCRT. The area under the curve (AUC) and cutoff analysis were used to evaluate model performance. RESULTS: A total of 155 patients were enrolled in this study, 82 in the training set and 73 in the testing set. The radiomics model was constructed based on two radiomics features, achieving AUCs of 0.968 (95%CI 0.933-0.992) in the training set and 0.885 (95%CI 0.800-0.958) in the testing set. The cutoff analysis resulted in an accuracy of 82.2% (95%CI 72.6-90.4%), a sensitivity of 75.0% (95%CI 58.3-91.7%), and a specificity of 85.7% (95%CI 75.5-96.0%) in the testing set. CONCLUSION: A machine learning model based on MR radiomics was developed and validated to accurately predict pCR after nCRT in patients with ESCC.

Apoptotic vesicles derived from human red blood cells promote bone regeneration via carbonic anhydrase 1.

Apoptotic vesicles (apoVs) are nanoscale vesicles derived from billions of apoptotic cells involved in the maintenance of the human body's homeostasis. Previous researches have shown that some apoVs, such as those derived from mesenchymal stem cells, contribute to bone formation. However, those apoVs cannot be extracted from patients in large quantities, and cell expansion is needed before apoV isolation, which limits their clinical translation. Mature RBCs, which have no nuclei or genetic material, are easy to obtain, showing high biological safety as a source of extracellular vesicles (EVs). Previous studies have demonstrated that RBC-derived EVs have multiple biological functions, but it is unknown whether RBCs produce apoVs and what effect these apoVs have on bone regeneration. In this study, we isolated and characterized RBC-derived apoVs (RBC-apoVs) from human venous blood and investigated their role in the osteogenesis of human bone mesenchymal stem cells (hBMSCs). We showed that RBCs could produce RBC-apoVs that expressed both general apoVs markers and RBC markers. RBC-apoVs significantly promoted osteogenesis of hBMSCs and enhanced bone regeneration in rat calvarial defects. Mechanistically, RBC-apoVs regulated osteogenesis by transferring carbonic anhydrase 1 (CA1) into hBMSCs and activating the P38 MAPK pathway. Our results indicated that RBC-apoVs could deliver functional molecules from RBCs to hBMSCs and promote bone regeneration, pointing to possible therapeutic use in bone tissue engineering.

Effect of storage temperature on the dimensional stability of DLP printed casts.

STATEMENT OF PROBLEM: Despite studies focusing on the accuracy and dimensional stability of additive manufacturing, research on the impact of storage conditions on these properties of 3-dimensional (3D) printed objects is lacking. PURPOSE: The purpose of this in vitro study was to investigate the influence of storage temperature on the dimensional stability of digital light processing (DLP) printed casts and to determine how different locations in printed casts react differently. MATERIAL AND METHODS: A completely dentate maxillary typodont model was digitized with a desktop laser scanner. The typodont was subsequently modified with a software program by adding cuboids with a side length of 3 mm on both maxillary central incisors, first molars, and second molars. The file was saved in the standard tessellation language (STL) format. The modified digitized typodont was then processed through the DLP technology printing process with a desktop DLP printer and photopolymerizing resin. The casts were printed 32 times and stored in sealed plastic bags, shielded from light, and subjected to 4 different temperature conditions (-20 °C, 4 °C, 20 °C, and 37 °C, n=8 each). The cuboids on the central incisors were labeled as the P1 group, first molars as the P2 group, and second molars as the P3 group. The distance between the cuboids was measured 5 times, with results recorded immediately after cast production and at 1, 2, 3, 5, 7, 14, and 28 days after. Repeated analysis of variance (ANOVA) and the Tukey honestly significant difference (HSD) test were used to compare the recorded values among the groups (α=.05). RESULTS: In the P1 group, the casts stored at -20 °C exhibited the smallest overall size change, with a mean ±standard deviation volume of 99.42 ±0.04% compared with the original casts after 28 days of storage. This was followed by the casts stored at 4 °C, 20 °C, and 37 °C, with remaining volumes of 99.39 ±0.06% (P=.139), 99.14 ±0.08% (P<.001), and 98.96 ±0.03% (P<.001), respectively. For the P2 and P3 groups, casts stored at 4 °C retained the most volume at 99.82 ±0.01%, whereas those stored at -20 °C, 20 °C, and 37 °C underwent greater changes, with remaining volumes of 99.66 ±0.03%, 100.32 ±0.02%, and 100.44 ±0.02%, respectively (P<.001). The P3 group exhibited a similar trend to that of the P2 group, with the casts stored at 4 °C remaining closest to the original dimensions at 99.86 ±0.02%, while casts stored at -20 °C showed 99.73 ±0.03% of the original volume and those stored at 20 °C and 37 °C expanded with volumes of 100.37 ±0.03% and 100.48 ±0.03%, respectively (P<.001). CONCLUSIONS: DLP printed casts stored at 4 °C exhibited the greatest overall dimensional stability, followed sequentially by those stored at -20 °C, 20 °C, and 37 °C. Additionally, the study confirmed that the posterior and anterior teeth regions of DLP printed casts respond differently to different storage temperatures.

CeO2 Nanoparticles to Promote Wound Healing: A Systematic Review.

Cerium (Ce) is a hot topic in the field of materials research due to its electronic layer structure and the unique antioxidant abilities of its oxide (CeO2 ). Cerium oxide nanoparticles (CeO2 NPs) demonstrate their potential as an antioxidant and antibacterial agent. Current research focuses on whether they can be used to promote wound healing and in what manner. This article provides a systematic review of the various forms of CeO2 NPs that are used in wound-healing materials over the past decade, as well as the effectiveness demonstrated by in vivo and in vitro experiments, with a focus on the relationship between concentration and effectiveness. CeO2 NPs are expected to become effective ingredients in dressings that require antibacterial, antioxidant, and wound healing promoting properties. This article serves as a reference for further research and clinical applications of nano-sized CeO2 in wound healing.

Zeolite imidazolate framework-8 in bone regeneration: A systematic review.

Zeolite imidazolate framework-8 (ZIF-8) is a biomaterial that has been increasingly studied in recent years. It has several applications such as bone regeneration, promotion of angiogenesis, drug loading, and antibacterial activity, and exerts multiple effects to deal with various problems in the process of bone regeneration. This systematic review aims to provide an overview of the applications and effectiveness of ZIF-8 in bone regeneration. A search of papers published in the PubMed, Web of Science, Embase, and Cochrane Library databases revealed 532 relevant studies. Title, abstract, and full-text screening resulted in 39 papers being included in the review, including 39 in vitro and 22 animal studies. Appropriate concentrations of nano ZIF-8 can promote cell proliferation and osteogenic differentiation by releasing Zn2+ and entering the cell, whereas high doses of ZIF-8 are cytotoxic and inhibit osteogenic differentiation. In addition, five studies confirmed that ZIF-8 exhibits good vasogenic activity. In all in vivo experiments, nano ZIF-8 promoted bone formation. These results indicate that, at appropriate concentrations, materials containing ZIF-8 promote bone regeneration more than materials without ZIF-8, and with characteristics such as promoting angiogenesis, drug loading, and antibacterial activity, it is expected to show promising applications in the field of bone regeneration. STATEMENT OF SIGNIFICANCE: This manuscript reviewed the use of ZIF-8 in bone regeneration, clarified the biocompatibility and effectiveness in promoting bone regeneration of ZIF-8 materials, and discussed the possible mechanisms and factors affecting its promotion of bone regeneration. Overall, this study provides a better understanding of the latest advances in the field of bone regeneration of ZIF-8, serves as a design guide, and contributes to the design of future experimental studies.

Platelet-Derived Apoptotic Vesicles Promote Bone Regeneration via Golgi Phosphoprotein 2 (GOLPH2)-AKT Signaling Axis.

Apoptotic vesicles (apoVs) are apoptotic-cell-derived nanosized vesicles that take on dominant roles in regulating bone homeostasis. We have demonstrated that mesenchymal stem cell (MSC)-derived apoVs are promising therapeutic agents for bone regeneration. However, clinical translation of MSC-derived apoVs has been hindered due to cell expansion and nuclear substance. As another appealing source for apoV therapy, blood cells could potentially eliminate these limitations. However, whether blood cells can release apoVs during apoptosis is uncertain, and the detailed characteristics and biological properties of respective apoVs are not elucidated. In this study, we showed that platelets (PLTs) could rapidly release abundant apoVs during apoptosis in a short time. To recognize the different protein expressions between PLT-derived apoVs and PLTs, we established their precise protein landscape. Furthermore, we identified six proteins specifically enriched in PLT-derived apoVs, which could be considered as specific biomarkers. More importantly, PLT-derived apoVs promoted osteogenesis of MSCs and rescued bone loss via Golgi phosphoprotein 2 (GOLPH2)-induced AKT phosphorylation, therefore, leading to the emergence of their potential in bone regeneration. In summary, we comprehensively determined characteristics of PLT-derived apoVs and confirmed their roles in bone metabolism through previously unrecognized GOPLH2-dependent AKT signaling, providing more understanding for exploring apoV-based therapy in bone tissue engineering.

Alkaline shear-thinning micro-nanocomposite hydrogels initiate endogenous TGFß signaling for in situ bone regeneration.

Recruiting endogenous stem cells to bone defects without stem cell transplantation and exogenous factor delivery represents a promising strategy for bone regeneration. Herein, we develop an alkaline shear-thinning micro-nanocomposite hydrogel (10-MmN), aiming to alkaline-activate endogenous TGFß1 and achieve in situ bone regeneration. It contains polyethyleneimine (PEI)-modified gelatin, laponite nanoplatelets (LAP), a bicarbonate buffer with a pH of 10, and gelatin microspheres (MSs). PEI-modified gelatin plays a pivotal role in hydrogel fabrication. It endows the system with sufficient positive charges, and forms a shear-thinning nanocomposite matrix in the pH 10 buffer (10-mN) with negatively charged LAP via electrostatic gelation. For biological functions, the pH 10 buffer dominates alkaline activation of endogenous serum TGFß1 to recruit rat bone marrow stem cells through the Smad pathway, followed by improved osteogenic differentiation. In addition, MSs are incorporated into 10-mN to form 10-MmN, and function as substrates to provide good attachment sites for the recruited stem cells and facilitate further their osteogenic differentiation. In a rat critical-sized calvarial defect model, 10-MmN exhibits excellent biocompatibility, biodegradability, hydrogel infusion and retention in bone defects with flexible shapes and active bleeding. Importantly, it repairs ~95% of the defect areas in 3 months by recruiting TGFßR2+ and CD90+CD146+ stem cells, and promoting cell proliferation, osteogenic differentiation and bone formation. The present study provides a biomaterial-based strategy to regulate alkalinity in bone defects for the initiation of endogenous TGFß signaling, which can be extended to treat other diseases.