Immunotherapy combined with apatinib in the treatment of advanced or metastatic gastric/gastroesophageal tumors: a systematic review and meta-analysis.

BACKGROUND: Immunotherapy or apatinib alone has been used as third-line adjuvant therapy for advanced or metastatic gastric/gastroesophageal junction (G/GEJ) tumors, but the efficacy of combining them with each other for the treatment of patients with advanced or metastatic G/GEJ is unknown; therefore, we further evaluated the efficacy and safety of immunotherapy combined with apatinib in patients with advanced or metastatic G/GEJ. METHODS: The main search was conducted on published databases: Embase, Cochrane library, PubMed.The search was conducted from the establishment of the database to December 2023.Clinical trials with patients with advanced or metastatic G/GEJ and immunotherapy combined with apatinib as the study variable were collected. Review Manager 5.4 software as well as stata 15.0 software were used for meta-analysis. RESULTS: A total of 651 patients from 19 articles were included in this meta-analysis. In the included studies, immunotherapy combined with apatinib had a complete response (CR) of 0.03 (95% CI: 0.00 -0.06), partial response (PR) of 0.34 (95% CI: 0.19-0.49), stable disease (SD) of 0.43 (95% CI: 0.32-0.55), objective response rate (ORR) was 0.36 (95% CI: 0.23-0.48), disease control rate (DCR) was 0.80 (95% CI: 0.74-0.86), and median progression-free survival (PFS) was 4.29 (95% CI: 4.05-4.52), median Overall survival (OS) was 8.79 (95% CI: 7.92-9.66), and the incidence of grade ≥ 3 TRAEs was 0.34 (95% CI: 0:19-0.49). PR, ORR, DCR, median PFS and median OS were significantly higher in the immunotherapy and apatinib combination chemotherapy group (IAC) than in the immunotherapy combination apatinib group (IA). And the difference was not significant in the incidence of SD and grade ≥ 3 TRAEs. CONCLUSION: This meta-analysis shows that immunotherapy combined with apatinib is safe and effective in the treatment of advanced or metastatic G/GEJ, where IAC can be a recommended adjuvant treatment option for patients with advanced or metastatic G/GEJ. However, more large multicenter randomized studies are urgently needed to reveal the long-term outcomes of immunotherapy combined with apatinib treatment.

Radiomic features at Contrast-enhanced CT Predict Virus-driven Liver Fibrosis: A Multi-institutional Study.

BACKGROUND: Liver fibrosis is a major cause of morbidity and mortality among in chronic hepatitis patients. Radiomics, particularly of the spleen, may improve diagnostic accuracy and treatment strategies. External validations are necessary to ensure reliability and generalizability. METHODS: In this retrospective study, we developed three radiomics models using contrast-enhanced CT scans from 167 patients with liver fibrosis (training group) between January 2020 and December 2021. Radiomic features were extracted from arterial venous, portal venous, and equilibrium phase images. Recursive feature selection random forest (RFS-RF) and the least absolute shrinkage and selection operator (LASSO) logistic regression were used for feature selection and dimensionality reduction. Performance was assessed by area under the curve, C-index, calibration plots and decision curve analysis. External validation was performed on 114 patients from two institutions. RESULTS: Twenty-five radiomic features were significantly associated with fibrosis stage, with 80% of the top 10 features originating from portal venous phase spleen images. The radiomics models showed good performance in the validation cohort (C-indices: 0.723-0.808) and excellent calibration. Decision curve analysis indicated clinical benefits, with machine learning-based radiomics models (RFR-score and SVMR-score) providing more significant advantages. CONCLUSION: Radiomic features offer significant benefits over existing serum indices for staging virus-driven liver fibrosis, underscoring the value of radiomics in enhancing diagnostic accuracy. Specifically, radiomics analysis of the spleen presents additional noninvasive options for assessing fibrosis, highlighting its potential in improving patient management and outcomes.

Effect of hydrogel drug delivery system for treating ulcerative colitis: A preclinical meta-analysis.

Hydrogel drug delivery systems (DDSs) for treating ulcerative colitis (UC) have garnered attention. However, there is a lack of meta-analysis summarizing their effectiveness. Therefore, this study aimed to conduct a meta-analysis of pre-clinical evidence comparing hydrogel DDSs with free drug administration. Subgroup analyses were performed based on hydrogel materials (polysaccharide versus non-polysaccharide) and administration routes of the hydrogel DDSs (rectal versus oral). The outcome indicators included colon length, histological scores, tumor necrosis factor-α (TNF-α), zonula occludens protein 1(ZO-1), and area under the curve (AUC). The results confirmed the therapeutic enhancement of the hydrogel DDSs for UC compared with the free drug group. Notably, no significant differences were found between polysaccharide and non-polysaccharide materials, however, oral administration was found superior regarding TNF-α and AUC. In conclusion, oral hydrogel DDSs can serve as potential excellent dosage forms in oral colon -targeting DDSs, and in the design of colon hydrogel delivery systems, polysaccharides do not show advantages compared with other materials.

STPoseNet: A real-time spatiotemporal network model for robust mouse pose estimation.

Animal behavior analysis plays a crucial role in contemporary neuroscience research. However, the performance of the frame-by-frame approach may degrade in scenarios with occlusions or motion blur. In this study, we propose a spatiotemporal network model based on YOLOv8 to enhance the accuracy of key-point detection in mouse behavioral experimental videos. This model integrates a time-domain tracking strategy comprising two components: the first part utilizes key-point detection results from the previous frame to detect potential target locations in the subsequent frame; the second part employs Kalman filtering to analyze key-point changes prior to detection, allowing for the estimation of missing key-points. In the comparison of pose estimation results between our approach, YOLOv8, DeepLabCut and SLEAP on videos of three mouse behavioral experiments, our approach demonstrated significantly superior performance. This suggests that our method offers a new and effective means of accurately tracking and estimating pose in mice through spatiotemporal processing.

A multifunctional ionic liquid coating on 3D-Printed prostheses: Combating infection, promoting osseointegration.

Periprosthetic infection and mechanical loosening are two leading causes of implant failure in orthopedic surgery that have devastating consequences for patients both physically and financially. Hence, advanced prostheses to simultaneously prevent periprosthetic infection and promote osseointegration are highly desired to achieve long-term success in orthopedics. In this study, we proposed a multifunctional three-dimensional printed porous titanium alloy prosthesis coated with imidazolium ionic liquid. The imidazolium ionic liquid coating exhibited excellent bacterial recruitment property and near-infrared (NIR) triggered photothermal bactericidal activity, enabling the prosthesis to effectively trap bacteria in its vicinity and kill them remotely via tissue-penetrating NIR irradiation. In vivo anti-infection and osseointegration investigations in infected animal models confirmed that our antibacterial prosthesis could provide long-term and sustainable prevention against periprosthetic infection, while promoting osseointegration simultaneously. It is expected to accelerate the development of next-generation prostheses and improve patient outcomes after prosthesis implantation.

Study on the Correlation between Hcy and Hs-CRP Levels and Cognitive Function in Patients with Bipolar Disorder and Borderline Personality Disorder.

OBJECTIVE: This study aims to explore the correlation and clinical significance of homocysteine and high-sensitivity C-reactive protein levels with cognitive function in patients with bipolar disorder (BD) and borderline personality disorder (BPD). METHODS: Patients with BD admitted to our hospital from January 2022 to December 2022 were chosen retrospectively. BPD patients were categorized into comorbidity groups, while those without BPD were assigned to non-comorbidity groups, each consisting of 60 cases. Enzyme-linked immunosorbent assay (ELISA) was utilized to assess serum levels of homocysteine (Hcy) and high-sensitivity C-reactive protein (hs-CRP) in both patient groups. Clinical symptoms were evaluated by the Hamilton Depression Rating Scale (HAMD) and the Young Mania Rating Scale (YMRS). Cognitive function was evaluated and compared using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Pearson correlation analysis was performed on the correlation between patients' serum Hcy and hs-CRP levels and HAMD, YMRS, and RBANS scores. RESULTS: In the comorbidity group, patients exhibited significantly elevated serum Hcy and hs-CRP levels compared to the non-comorbidity group (p < 0.05). Patients in the comorbidity group displayed higher HAMD and YMRS scores than those in the non-comorbidity group (p < 0.05). Additionally, attention, speech, visual span, immediate memory, and delayed memory in the comorbidity group were notably lower than in the non-comorbidity group (p < 0.05). The speech, visual span, and immediate memory of RBANS in bipolar depressive patients with comorbid BPD were lower than those in bipolar depressive patients without comorbid BPD (p < 0.05), the speech of RBANS in bipolar manic patients with comorbid BPD was lower than those in bipolar manic patients without comorbid BPD (p < 0.05). Pearson correlation analysis showed that the expression of Hcy and hs-CRP in the comorbid group was positively correlated with HAMD and YMRS scores, and negatively correlated with attention, speech, visual span, immediate memory, and delayed memory, and these differences were statistically significant (p < 0.05). CONCLUSION: High serum Hcy and hs-CRP expression levels may regulate inflammatory responses, aggravating cognitive impairment in patients with BD and BPD. Serum Hcy and hs-CRP expression levels are significantly related to cognitive dysfunction. They are expected to guide the prevention and treatment of BD comorbid BPD patients.

Exploring the mechanism of ShenGui capsule in treating heart failure based on network pharmacology and molecular docking: A review.

ShenGui capsule (SGC), as a herbal compound, has significant effects on the treatment of heart failure (HF), but its mechanism of action is unclear. In this study, we aimed to explore the potential pharmacological targets and mechanisms of SGC in the treatment of HF using network pharmacology and molecular docking approaches. Potential active ingredients of SGC were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform database and screened by pharmacokinetic parameters. Target genes of HF were identified by comparing the toxicogenomics database, GeneCards, and DisGeNET databases. Protein interaction networks and gene-disorder-target networks were constructed using Cytoscape for visual analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes were also performed to identify protein functional annotations and potential target signaling pathways through the DAVID database. CB-DOCK was used for molecular docking to explore the role of IL-1ß with SGC compounds. Sixteen active ingredients in SGC were screened from the traditional Chinese medicine systems pharmacology database and analysis platform, of which 36 target genes intersected with HF target genes. Protein-protein interactions suggested that each target gene was closely related, and interleukin-1ß (IL-1ß) was identified as Hub gene. The network pharmacology analysis suggested that these active ingredients were well correlated with HF. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that target genes were highly enriched in pathways such as inflammation. Molecular docking results showed that IL-1ß binds tightly to SGC active components. This experiment provides an important research basis for the mechanism of action of SGC in the treatment of HF. In this study, the active compounds of SGC were found to bind IL-1ß for the treatment of heart failure.

Modulation of the microhomology-mediated end joining pathway suppresses large deletions and enhances homology-directed repair following CRISPR-Cas9-induced DNA breaks.

BACKGROUND: CRISPR-Cas9 genome editing often induces unintended, large genomic rearrangements, posing potential safety risks. However, there are no methods for mitigating these risks. RESULTS: Using long-read individual-molecule sequencing (IDMseq), we found the microhomology-mediated end joining (MMEJ) DNA repair pathway plays a predominant role in Cas9-induced large deletions (LDs). We targeted MMEJ-associated genes genetically and/or pharmacologically and analyzed Cas9-induced LDs at multiple gene loci using flow cytometry and long-read sequencing. Reducing POLQ levels or activity significantly decreases LDs, while depleting or overexpressing RPA increases or reduces LD frequency, respectively. Interestingly, small-molecule inhibition of POLQ and delivery of recombinant RPA proteins also dramatically promote homology-directed repair (HDR) at multiple disease-relevant gene loci in human pluripotent stem cells and hematopoietic progenitor cells. CONCLUSIONS: Our findings reveal the contrasting roles of RPA and POLQ in Cas9-induced LD and HDR, suggesting new strategies for safer and more precise genome editing.

Single-cell RNA sequencing reveals cell-cell communication and potential biomarker in sepsis and septic shock patients.

BACKGROUND: Sepsis is a disease characterized by infection-induced multiorgan dysfunction, which can progress to septic shock if not promptly treated. Early identification of sepsis is crucial for its treatment. However, there are currently limited specific biomarkers for sepsis or septic shock. This study aims to identify potential biomarkers for sepsis and septic shock. METHODS: We analyzed single-cell transcriptomic data of peripheral blood mononuclear cells (PBMCs) from healthy individuals, sepsis and septic shock patients, identified differences in gene expression and cell-cell communication between different cell types during disease progression. Moreover, our analyses were further validated with flow cytometry and bulk RNA-seq data. RESULTS: Our study elucidates the alterations in cellular proportions and cell-cell communication among healthy controls, sepsis, and septic shock patients. We identified a specific augmentation in the Resistin signaling within sepsis monocytes, mediated via RETN-CAP1 ligand-receptor pairs. Additionally, we observed enhanced IL16 signaling within monocytes from septic shock patients, mediated through IL16-CD4 ligand-receptor pairs. Subsequently, we confirmed our findings by validating the increase in CAP-1+ monocytes in sepsis and IL16+ monocytes in septic shock in mouse models. And a significant upregulation of CAP-1 and IL16 was also observed in the bulk RNA-seq data from patients with sepsis and septic shock. Furthermore, we identified four distinct clusters of CD14+ monocytes, highlighting the heterogeneity of monocytes in the progress of sepsis. CONCLUSIONS: In summary, our work demonstrates changes in cell-cell communication of healthy controls, sepsis and septic shock, confirming that the molecules CAP-1 and IL16 on monocytes may serve as potential diagnostic markers for sepsis and septic shock, respectively. These findings provide new insights for early diagnosis and stratified treatment of the disease.

BRG1 programs PRC2-complex repression and controls oligodendrocyte differentiation and remyelination.

Chromatin-remodeling protein BRG1/SMARCA4 is pivotal for establishing oligodendrocyte (OL) lineage identity. However, its functions for oligodendrocyte-precursor cell (OPC) differentiation within the postnatal brain and during remyelination remain elusive. Here, we demonstrate that Brg1 loss profoundly impairs OPC differentiation in the brain with a comparatively lesser effect in the spinal cord. Moreover, BRG1 is critical for OPC remyelination after injury. Integrative transcriptomic/genomic profiling reveals that BRG1 exhibits a dual role by promoting OPC differentiation networks while repressing OL-inhibitory cues and proneuronal programs. Furthermore, we find that BRG1 interacts with EED/PRC2 polycomb-repressive-complexes to enhance H3K27me3-mediated repression at gene loci associated with OL-differentiation inhibition and neurogenesis. Notably, BRG1 depletion decreases H3K27me3 deposition, leading to the upregulation of BMP/WNT signaling and proneurogenic genes, which suppresses OL programs. Thus, our findings reveal a hitherto unexplored spatiotemporal-specific role of BRG1 for OPC differentiation in the developing CNS and underscore a new insight into BRG1/PRC2-mediated epigenetic regulation that promotes and safeguards OL lineage commitment and differentiation.

Long-lived nitric oxide molecular tagging velocimetry with 1 + 1 REMPI.

The successful demonstration of long-lived nitric oxide (NO) fluorescence for molecular tagging velocimetry (MTV) measurements is described in this Letter. Using 1 + 1 resonance-enhanced multiphoton ionization (REMPI) of NO at a wavelength near 226 nm, targeting the overlapping Q1(7) and Q21(7) lines of the A-X (0, 0) electronic system, the lifetime of the NO MTV signal was observed to be approximately 8.6 µs within a 100-Torr cell containing 2% NO in nitrogen. This is in stark contrast to the commonly reported single photon NO fluorescence, which has a much shorter calculated lifetime of approximately 43 ns at this pressure and NO volume fraction. While the shorter lifetime fluorescence can be useful for molecular tagging velocimetry with single laser excitation within very high-speed flows at some thermodynamic conditions, the longer lived fluorescence shows the potential for an order of magnitude more accurate and precise velocimetry, particularly within lower speed regions of hypersonic flow fields such as wakes and boundary layers. The physical mechanism responsible for the generation of this long-lived signal is detailed. Furthermore, the effectiveness of this technique is showcased in a high-speed jet flow, where it is employed for precise flow velocity measurements.

Poria cocos polysaccharides improve alcoholic liver disease by interfering with ferroptosis through NRF2 regulation.

The active ingredient in Poria cocos, a parasitic plant belonging to the family Polyporaceae, is Poria cocos polysaccharide (PCP). PCP exhibits liver protection and anti-inflammatory effects, although its effect on alcoholic liver disease (ALD) remains unstudied. This study investigated the mechanism of PCP in improving ALD by regulating the Nrf2 signaling pathway. After daily intragastric administration of high-grade liquor for 4 hours, each drug group received PCPs or the ferroptosis inhibitor ferrostatin-1. The Nrf2 inhibitor ML385 (100 mg/kg/day) group was intraperitoneally injected, after which PCP (100 mg/kg/day) was administered by gavage. Samples were collected after 6 weeks for liver function and blood lipid analysis using an automatic biochemical analyzer. In the alcoholic liver injury cell model established with 150 mM alcohol, the drug group was pretreated with PCP, Fer-1, and ML385, and subsequent results were analyzed. The results revealed that PCP intervention significantly reduced liver function and blood lipid levels in alcohol-fed rats, along with decreased lipid deposition. PCP notably enhanced Nrf2 signaling expression, regulated oxidative stress levels, inhibited NF-κß, and its downstream inflammatory signaling pathways. Furthermore, PCP upregulated FTH1 protein expression and reduced intracellular Fe2+, suggesting an improvement in ferroptosis. In vitro studies yielded similar results, indicating that PCP can reduce intracellular ferroptosis by regulating oxidative stress and improve alcoholic liver injury by inhibiting the production of inflammatory factors.

Molecular insight into T cell exhaustion in hepatocellular carcinoma.

Hepatocellular carcinoma is one of the leading causes of cancer-related mortality globally. The emergence of immunotherapy has been shown to be a promising therapeutic approach for hepatocellular carcinoma in recent years. It has been well known that T cell plays a key role in current immunotherapy. However, sustained exposure to antigenic stimulation within the tumor microenvironment may lead to T cell exhaustion, which may cause treatment ineffectiveness. Therefore, reversing T cell exhaustion has been an important issue for the clinical application of immunotherapy, and a comprehensive understanding of the intricacies surrounding T cell exhaustion and its underlying mechanisms is imperative for devising strategies to overcome the T cell exhaustion during treatment. In this review, we summarized the reported drivers of T cell exhaustion in hepatocellular carcinoma and delineate potential ways to reverse it. Additionally, we discussed the interplay among metabolic plasticity, epigenetic regulation, and transcriptional factors in exhausted T cells in hepatocellular carcinoma, and their implication for future clinical applications.

Eubacterium rectale is a potential marker of altered gut microbiota in psoriasis and psoriatic arthritis.

Previous studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients. IMPORTANCE: In this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.

Evaluation of neoadjuvant immunotherapy in resectable gastric/gastroesophageal junction tumors: a meta-analysis and systematic review.

Background: Neoadjuvant therapy for resectable gastric cancer/gastroesophageal junction tumors is progressing slowly. Although immunotherapy for advanced gastric cancer/gastroesophageal junction tumors has made great progress, the efficacy and safety of neoadjuvant immunotherapy for locally resectable gastric cancer/gastroesophageal junction tumors have not been clearly demonstrated. Here, we conducted a systematic review and meta-analysis to assess the efficacy and safety of neoadjuvant immunotherapy and advance the current research. Methods: Original articles describing the safety and efficacy of neoadjuvant immunotherapy for resectable gastric cancer/gastroesophageal junction tumors published up until October 15, 2023 were retrieved from PubMed, Embase, the Cochrane Library, and other major databases. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated for heterogeneity and subgroup analysis. Results: A total of 1074 patients from 33 studies were included. The effectiveness of neoadjuvant immunotherapy was mainly evaluated using pathological complete remission (PCR), major pathological remission (MPR), and tumor regression grade (TRG). Among the included patients, 1015 underwent surgical treatment and 847 achieved R0 resection. Of the patients treated with neoadjuvant immunotherapy, 24% (95% CI: 19%-28%) achieved PCR and 49% (95% CI: 38%-61%) achieved MPR. Safety was assessed by a surgical resection rate of 0.89 (95% CI: 85%-93%), incidence of ≥ 3 treatment-related adverse events (TRAEs) of 28% (95% CI: 17%-40%), and incidence of ≥ 3 immune-related adverse events (irAEs) of 19% (95% CI: 11%-27%). Conclusion: Neoadjuvant immunotherapy, especially neoadjuvant dual-immunotherapy combinations, is effective and safe for resectable gastric/gastroesophageal junction tumors in the short term. Nevertheless, further multicenter randomized trials are required to demonstrate which combination model is more beneficial. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=358752, identifier CRD42022358752.

A method for studying escape behavior to terrestrial threats in rodents.

BACKGROUND: Escape is one of the most essential behaviors for an animal's survival because it could be a matter of life and death. Much of our current understanding of the neural mechanisms underlying escape is derived from the looming paradigm, which mimics a diving aerial predator. Yet, the idea of the looming paradigm does not account for all types of threats like lions hunting antelopes or cats stalking mice. Escape responses to such terrestrial threats may require different strategies and neural mechanisms. NEW METHODS: Here, we developed a real-time interactive platform to study escape behavior to terrestrial threats in mice. A closed-loop controlled robot was magnetically pulled to mimic a terrestrial threat that chases a mouse. By using strong magnets and high-precision servo motors, the robot is capable of moving precisely with a high spatial-temporal resolution. Different algorithms can be used to achieve single approach or persistent approach. RESULTS: Animal experiments showed that mice exhibited consistent escape behavior when exposed to an approaching robotic predator. When presented with a persistently approaching predator, the mice were able to rapidly adapt their behavior, as evidenced by a decrease in startle responses and changes in movement patterns. COMPARISON WITH EXISTING METHODS: In comparison to existing methods for studying escape behavior, such as the looming paradigm, this approach is more suitable for investigating animal behavior in response to sustained threats. CONCLUSION: In conclusion, we have developed a flexible platform to study escape behavior to terrestrial threats in mice.

Stabilizing 3D-printed metal alloys.

A design strategy overcomes the strength-ductility trade-off in alloy manufacturing.

Novel-Ink-Based Direct Ink Writing of Ti6Al4V Scaffolds with Sub-300 µm Structural Pores for Superior Cell Proliferation and Differentiation.

Ti6Al4V scaffolds with pore sizes between 300 and 600 µm are deemed suitable for bone tissue engineering. However, a significant proportion of human bone pores are smaller than 300 µm, playing a crucial role in cell proliferation, differentiation, and bone regeneration. Ti6Al4V scaffolds with these small-sized pores are not successfully fabricated, and their cytocompatibility remains unknown. The study presents a novel ink formula specifically tailored for fabricating Ti6Al4V scaffolds featuring precise and unobstructed sub-300 µm structural pores, achieved by investigating the rheological properties and printability of five inks containing 60-77.5 vol% Ti6Al4V powders and bisolvent binders. Ti6Al4V scaffolds with 50-600 µm pores are fabricated via direct ink writing and subjected to in vitro assays with MC3T3-E1 and bone marrow mesenchymal stem cells. The 100 µm pore-sized scaffolds exhibit the highest cell adhesion and proliferation capacity based on live/dead assay, FITC-phalloidin/4',6-diamidino-2-phenylindole staining, and cell count kit 8 assay. The alizarin red staining, real-time quantitative PCR assay, and immunocytochemical staining demonstrate the superior osteogenic differentiation potential of 100 and 200 µm pore-sized scaffolds. The importance of sub-300 µm structrual pores is highlighted, redefining the optimal pore size for Ti6Al4V scaffolds and advancing bone tissue engineering and clinical medicine development.

Study on Osseointegration Capability of ß-Type Ti-Nb-Zr-Ta-Si Alloy for Orthopedic Implants.

Osseointegration is the basic condition for orthopedic implants to maintain long-term stability. In order to achieve osseointegration, a low elastic modulus is the most important performance indicator. It is difficult for traditional titanium alloys to meet this requirement. A novel ß-titanium alloy (Ti-35Nb-7Zr-5Ta)98Si2 was designed, which had excellent strength (a yield strength of 1296 MPa and a breaking strength 3263 MPa), an extremely low elastic modulus (37 GPa), and did not contain toxic elements. In previous in vitro studies, we confirmed the good biocompatibility of this alloy and similar bioactivity to Ti-6Al-4V, but no in vivo study was performed. In this study, Ti-6Al-4V and (Ti-35Nb-7Zr-5Ta)98Si2 were implanted into rabbit femurs. Imaging evaluation and histological morphology were performed, and the bonding strength and bone contact ratio of the two alloys were measured and compared. The results showed that both alloys remained in their original positions 3 months after implantation, and neither imaging nor histological observations found inflammatory reactions in the surrounding bone. The bone-implant contact ratio and bonding strength of (Ti-35Nb-7Zr-5Ta)98Si2 were significantly higher than those of Ti-6Al-4V. The results confirmed that (Ti-35Nb-7Zr-5Ta)98Si2 has a better osseointegration ability than Ti-6Al-4V and is a promising material for orthopedic implants.

Functionalized biomimetic mineralized collagen promotes osseointegration of 3D-printed titanium alloy microporous interface.

Mineralized collagen (MC) is the fundamental unit of natural bone tissue and can induce bone regeneration. Unmodified MC has poor mechanical properties and a single component, making it unable to cope with complex physiological environment. In this study, we introduced sodium alginate (SA) and vascular endothelial growth factor (VEGF) into the MC material to construct functionalized mineralized collagen (FMC) with good mechanical strength and the ability to continuously release growth factors. The FMC is filled into the pores of 3D printed titanium alloy scaffold to form a new organic-inorganic bioactive interface. With the continuous degradation of FMC, bone marrow mesenchymal stem cells (BMSCs) and vascular endothelial cells (VECs) in the surrounding environment are recruited to the surface of the scaffold to promote bone and vascular regeneration. After implanting the scaffold into the distal femoral defect of rabbits, Micro CT, histological, push-out, as well as immunohistochemical analysis showed that the composite interface can significantly promote osseointegration. These findings provide a new strategy for the development and application of mineralized collagen materials.