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In tumor metastasis, the margination and adhesion of tumor cells are two critical and closely related steps, which may determine the destination where the tumor cells extravasate to. We performed a direct three-dimensional simulation on the behaviors of the tumor cells in a real microvascular network, by a hybrid method of the smoothed dissipative particle dynamics and immersed boundary method (SDPD-IBM). The tumor cells are found to adhere at the microvascular bifurcations more frequently, and there is a positive correlation between the adhesion of the tumor cells and the wall-directed force from the surrounding red blood cells (RBCs). The larger the wall-directed force is, the closer the tumor cells are marginated towards the wall, and the higher the probability of adhesion behavior happen is. A relatively low or high hematocrit can help to prevent the adhesion of tumor cells, and similarly, increasing the shear rate of blood flow can serve the same purpose. These results suggest that the tumor cells may be more likely to extravasate at the microvascular bifurcations if the blood flow is slow and the hematocrit is moderate.

Guided bone regeneration (GBR) is a widely used technique for alveolar bone augmentation. Among all the principal elements, barrier membrane is recognized as the key to the success of GBR. Ideal barrier membrane should have satisfactory biological and mechanical properties. According to their composition, barrier membranes can be divided into polymer membranes and non-polymer membranes. Polymer barrier membranes have become a research hotspot not only because they can control the physical and chemical characteristics of the membranes by regulating the synthesis conditions but also because their prices are relatively low. Still now the bone augment effect of barrier membrane used in clinical practice is more dependent on the body’s own growth potential and the osteogenic effect is difficult to predict. Therefore, scholars have carried out many researches to explore new barrier membranes in order to improve the success rate of bone enhancement. The aim of this study is to collect and compare recent studies on optimizing barrier membranes. The characteristics and research progress of different types of barrier membranes were also discussed in detail.

Implant-associated infection (IAI) is one of the major challenges in orthopedic surgery. The development of implants with inherent antibacterial properties is an effective strategy to resolve this issue. In recent years, biodegradable alloy materials have received considerable attention because of their superior comprehensive performance in the field of orthopedic implants. Studies on biodegradable alloy orthopedic implants with antibacterial properties have gradually increased. This review summarizes the recent advances in biodegradable magnesium- (Mg-), iron- (Fe-), and zinc- (Zn-) based alloys with antibacterial properties as orthopedic implant materials. The antibacterial mechanisms of these alloy materials are also outlined, thus providing more basis and insights on the design and application of biodegradable alloys with antibacterial properties as orthopedic implants.

Ti-5Cu alloy has been proved to have excellent mechanical properties and cell compatibility and has certain antibacterial properties due to the addition of Cu. However, there are few studies on the effects of Ti-5Cu alloy on macrophage polarization and immune-related bone formation. In this study, we prepared Ti-5Cu alloy by three-dimensional printing technology and found that Ti-5Cu alloy presented a much smoother surface compared with Ti. In addition, the CCK-8 results indicated the Ti-5Cu alloy had no cytotoxicity to RAW264.7 cells by co-culture. The results of inductively coupled plasma mass spectrometry showed that the concentration of Cu 2+ was 0.133 mg/L after 7 days of co-culture, and the CCK-8 results proved that Cu 2+ had no cytotoxicity to RAW264.7 at this concentration. Then, we studied the effects of Ti-5Cu alloy on macrophage polarization; it was shown that the Ti-5Cu alloy is more prone to modulate the RAW264.7 polarization towards the M2 phenotype and the conditioned medium derived from Ti-5Cu alloy significantly promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells. However, when the expression of Oncostatin M (OSM) gene of RAW264.7 was knocked down, the osteogenic differentiation of MC3T3-E1 cells was decreased. This suggests that the OSM secreted by RAW264.7 co-cultured with Ti-5Cu alloy could accelerate the osteogenic differentiation of MC3T3-E1 cells by acting on OSMR/gp130 receptors.

Exosomes are nano-sized extracellular vesicles (EVs) released by diverse types of cells, which affect the functions of targeted cells by transporting bioactive substances. As the main component of exosomes, non-coding RNA (ncRNA) is demonstrated to impact multiple pathways participating in bone healing. Herein, this review first introduces the biogenesis and secretion of exosomes, and elucidates the role of the main cargo in exosomes, ncRNAs, in mediating intercellular communication. Subsequently, the potential molecular mechanism of exosomes accelerating bone healing is elucidated from the following four aspects: macrophage polarization, vascularization, osteogenesis and osteoclastogenesis. Then, we systematically introduce construction strategies based on modified exosomes in bone regeneration field. Finally, the clinical trials of exosomes for bone healing and the challenges of exosome-based therapies in the biomedical field are briefly introduced, providing solid theoretical frameworks and optimization methods for the clinical application of exosomes in orthopedics. Graphical abstract

Large bone defects are a major global health concern. Bone tissue engineering (BTE) is the most promising alternative to avoid the drawbacks of autograft and allograft bone. Nevertheless, how to precisely control stem cell osteogenic differentiation has been a long-standing puzzle. Compared with biochemical cues, physicomechanical stimuli have been widely studied for their biosafety and stability. The mechanical properties of various biomaterials (polymers, bioceramics, metal and alloys) become the main source of physicomechanical stimuli. By altering the stiffness, viscoelasticity, and topography of materials, mechanical stimuli with different strengths transmit into precise signals that mediate osteogenic differentiation. In addition, externally mechanical forces also play a critical role in promoting osteogenesis, such as compression stress, tensile stress, fluid shear stress and vibration, etc. When exposed to mechanical forces, mesenchymal stem cells (MSCs) differentiate into osteogenic lineages by sensing mechanical stimuli through mechanical sensors, including integrin and focal adhesions (FAs), cytoskeleton, primary cilium, ions channels, gap junction, and activating osteogenic-related mechanotransduction pathways, such as yes associated proteins (YAP)/TAZ, MAPK, Rho-GTPases, Wnt/β-catenin, TGFβ superfamily, Notch signaling. This review summarizes various biomaterials that transmit mechanical signals, physicomechanical stimuli that directly regulate MSCs differentiation, and the mechanical transduction mechanisms of MSCs. This review provides a deep and broad understanding of mechanical transduction mechanisms and discusses the challenges that remained in clinical translocation as well as the outlook for the future improvements.

Improving the filtration efficiency of air filter materials is an ongoing research goal. This study conducted in-depth research on a new reduced graphene oxide air filter material, and the differences in its performance and conductivity durability before and after eliminating static electricity were tested and analyzed. The results showed that the filtration efficiency of the reduced graphene oxide air filter material significantly decreased after eliminating static electricity. The maximum decrease in filtration efficiency was observed at a filtration velocity of 0.8 m/s, with PM10 > PM1.0 > PM2.5. In this case, the filtration efficiency decreased by 11.8%, 7.98%, and 7.17%, respectively. The maximum difference in filtration efficiency of 0.29 μm particulates was about 12.7%. Eliminating static electricity slightly increased the resistance (2.5~15.5 Pa). In addition, the new reduced graphene oxide air filter material exhibited good conductivity and stability after continuous testing. This study provides data support for the application of subsequent electrification sterilization, reference values for multi-angle applications, and the development of new composite air filter materials.

Microfluidic chips have been widely used to probe the mechanical properties of cells, which are recognized as a promising label-free biomarker for some diseases. In our previous work (Ye et al., 2018), we have studied the relationships between the transit time and the mechanical properties of a cell flowing through a microchannel with a single constriction, which potentially forms a basis for a microfluidic chip to measure cell’s mechanical properties. Here, we investigate this microfluidic chip design and examine its potential in performances. We first develop the simultaneous dependence of the transit time on both the shear and bending moduli of a cell, and then examine the chip sensitivity with respect to the cell mechanical properties while serializing a single constriction along the flow direction. After that, we study the effect of the flow velocity on the transit time, and also test the chip’s ability to identify heterogeneous cells with different mechanical properties. The results show that the microfluidic chip designed is capable of identifying heterogeneous cells, even when only one unhealthy cell is included. The serialization of chip can greatly increase the chip sensitivity with respect to the mechanical properties of cells. The flow with a higher velocity helps in not only promoting the chip throughput, but also in providing more accurate transit time measurements, because the cell prefers a symmetric deformation under a high velocity.

Abstract In recent decades, bone tissue engineering, which is supported by scaffold, seed cells and bioactive molecules (BMs), has provided new hope and direction for treating bone defects. In terms of seed cells, compared to bone marrow mesenchymal stem cells, which were widely utilized in previous years, adipose-derived stem cells (ADSCs) are becoming increasingly favored by researchers due to their abundant sources, easy availability and multi-differentiation potentials. However, there is no systematic theoretical basis for selecting appropriate biomaterials loaded with ADSCs. In this review, the regulatory effects of various biomaterials on the behavior of ADSCs are summarized from four perspectives, including biocompatibility, inflammation regulation, angiogenesis and osteogenesis, to illustrate the potential of combining various materials with ADSCs for the treatment of bone defects. In addition, we conclude the influence of additional application of various BMs on the bone repair effect of ADSCs, in order to provide more evidences and support for the selection or preparation of suitable biomaterials and BMs to work with ADSCs. More importantly, the associated clinical case reports and experiments are generalized to provide additional ideas for the clinical transformation and application of bone tissue engineering loaded with ADSCs. Graphical abstract

pneumonia (PJP) shows a high fatality rate in non-HIV patients. However, there are limited data on drug resistance-related gene mutations in these patients. This study aimed to describe the prevalence of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of in non-HIV patients in China, providing a reference for drug usage. We analyzed the polymorphisms of DHPS and DHFR genes from 45 non-HIV patients in China, including infection (n = 14) and colonization (n = 31). This analysis also considered clinical characteristics, burden, treatment response, and prognosis. Compared to the colonization, infection had significantly altered blood indicators (GR%, LY%, HGB, TP, ALB, CRP, <0.05) with higher burden ( <0.05) and worse prognosis ( <0.05). Additionally, patients with infection were more susceptible to infections, such as the Epstein-Barr virus, Cytomegalovirus, Mycoplasma and Klebsiella pneumoniae. Although no known drug-resistance mutations were detected in the DHPS gene in this study, 10 nonsynonymous mutations were identified. Furthermore, 10 nonsynonymous and 2 synonymous mutations were found in the DHFR gene. However, these mutations were not associated with a worse prognosis. Our results implied that TMP-SMX prophylaxis is still recommended for PJP in high-risk non-HIV patients in China.