Design an implant similar to the human bone is one of the critical problems in bone tissue engineering. Metal porous scaffolds have good prospects in bone tissue replacement due to their matching ...elastic modulus, better strength, and biocompatibility. However, traditional processing methods are challenging to fabricate scaffolds with a porous structure, limiting the development of porous scaffolds. With the advancement of additive manufacturing (AM) and computer-aided technologies, the development of porous metal scaffolds also ushers in unprecedented opportunities. In recent years, many new metal materials and innovative design methods are used to fabricate porous scaffolds with excellent mechanical properties and biocompatibility. This article reviews the research progress of porous metal scaffolds, and introduces the AM technologies used in porous metal scaffolds. Then the applications of different metal materials in bone scaffolds are summarized, and the advantages and limitations of various scaffold design methods are discussed. Finally, we look forward to the development prospects of AM in porous metal scaffolds.
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•Deformation mechanisms and fracture modes of gradient porous NiTi alloys based on different unit cells were comprehensively investigated.•At about 50 % porosity, the I structure ...exhibited an abnormally high compressive strength, over twice that of the G and D structures.•Such a large gap in compressive strength was mainly due to their distinct strain heterogeneity and macrostructural stability.•There was a significant difference in the deformation mechanisms activated at the edge and center struts under an external strain of 20 %.
Gradient porous structures based on triply periodic minimal surfaces offer exceptional specific strength and multi-functionality. However, strain heterogeneity complicates their deformation mechanisms and fracture modes. In this study, we fabricated a series of gradient porous NiTi alloys based on gyroid (G), diamond (D), and I-WP (I) unit cells, with porosities ranging from 50% to 70%. Surprisingly, the I structure exhibited an abnormally high compressive strength of nearly 600 MPa at around 50% porosity, more than twice that of the G and D structures. This performance gap was attributed to the activation of mixed deformation mechanisms and distinct fracture modes. While the G structure showed a uniform radial strain distribution, the D and I structures displayed pronounced radial strain gradients with concentrated central strains. The D structure deformed through relative sliding of oblique struts, while the I structure maintained macrostructural stability, with thick edge struts providing continuous strain hardening until monolithic fracture. This unique deformation behavior results from the synergistic effects of its intrinsic macrostructural stability, significant radial strain gradients, and sufficiently thicker edge struts. The integration of metallurgical and architectural design principles represents a novel approach to tailoring the mechanical properties of gradient porous metals for advanced applications.
Bone Marrow mesenchymal Stem Cells (BMSCs) are considered as an important source of cells for regenerative medicine, In particular, Bone Marrow mesenchymal Stem Cells Exosomes (BMSCs-EXO) have the ...most significant effect in the treatment of Spinal Cord Injury (SCI), but the mechanism of action is still unknown. This study found that compared with other SCI groups, BMSCs-EXO loaded with miR-146a could significantly improve the functional recovery of the hind limbs of SCI rats. Hematoxylin and eosin (H&E) indicated that the lesion area of spinal cord injury was less, nissl staining indicated that the number of nissl bodies remained more; the mechanism may be through inhibiting the expression of IRAK1 and TRAF6, blocking the activation of NF-κB p65, reducing the expression of TNF-α, IL-1β and IL-6 inflammatory factors and oxidative stress, improving the SCI microenvironment, and promoting the repair of neural function. In general, we found that BMSCs-EXO loaded with miR-146a could reduce the inflammatory response and oxidative stress in SCI by inhibiting the activation of IRAK1/TRAF6/NF-κB p65 signaling pathway, and promote the recovery of neurological function in SCI rats.
•Ti/Zn composites had enhanced mechanical properties.•The biointerface between the fine grain surface and the macrophages was remodeled.•The released Zn ions mediated the bioenergetic remodeling of ...macrophages.•The immunomodulation of Ti/Zn composites promoted the efficiency of osseointegration.
The remodeling of macrophages mediated by biomaterials is an important step in osseointegration. The biointerfacial characteristics shaped by implants and the bioenergetic state derived from macrophages are considered the key to macrophage reprogramming. In this study, the integrated Ti/Zn composites with optimized morphology and bioactive phase were prepared by friction stir processing, which could meet the multi-biofunctional requirements in the application of narrow-diameter implants. The severe plastic deformation and the hindrance of Zn particles to grain growth promote grain refinement, resulting in enhanced mechanical properties. The cell interfacial adhesion mediated by the grain boundary collaborated the energy metabolism reprogramming induced by the released Zn ion, promoting jointly anti-inflammatory cascade in macrophages and favorable osteogenesis in bone marrow mesenchymal stem cells (BMSCs). This study provides a new simultaneous approach of morphology and composition modification for titanium implants, and reveals the important role of grain size and bioactive element in the reversion of macrophage fate as well.
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The imbalance between osteogenesis and adipogenesis in the bone marrow is the main characteristic of osteoporosis (OP). Thus, exploring regulation of the differentiation of bone marrow stromal cells ...(BMSCs) into osteoblasts and adipocytes is important to identify novel targets for the treatment of OP. In the present study, the master regulator of endoplasmic reticulum (ER) stress, heat shock protein family A (Hsp70) member 5 (HSPA5) was shown to significantly accumulate in osteoblasts and adipocytes, but not in osteoclasts in bone sections from aged and postmenopausal OP mice. In vitro study revealed that HSPA5 negatively modulated osteogenic differentiation and positively promoted adipogenic differentiation, and that targeting HSPA5 with its inhibitor HA15 enhanced osteogenic differentiation and inhibited adipogenic differentiation. Also, HA15 treatment induces ER stress and autophagy, and decreases apoptosis in cells. We constructed a postmenopausal OP model in mice with ovariectomy surgery, and treated the mice with HA15. The results showed that HA15 treatment induced appropriate ER stress, activated autophagy and decreased apoptosis in osteoblasts, thereby alleviating bone loss in vivo. Our results indicated that HSPA5 participated in OP pathogenesis by regulating the differentiation of BMSCs. HSPA5 may serve as a new target for the treatment of OP, and targeting HSPA5 with HA15 prevents the progression of OP and provides a candidate therapeutic molecule for postmenopausal OP.
Osteoporosis (OP) is characterized by decreased bone mineral density and impaired bone strength. Carfilzomib (CFZ) is a new-generation proteasome inhibitor and has been found to affect bone ...metabolism. However, the effect and mechanism of CFZ on OP has not been investigated systematically. In this study, we found that protein levels of proteasome activator subunit 1/2 (PSME1/2) increased in OP, and accumulated mostly in osteoblasts and osteoclasts. Treatment with PSME1/2 recombinant protein inhibited osteogenesis and promoted osteoclast formation in vitro. Also, PSME1/2 inhibited the expression of β-catenin protein, resulting in limitation of Wnt/β-catenin signaling. CFZ inhibited PSME1 and PSME2 proteasome activities and increased β-catenin protein level, resulting in the translocation of β-catenin to the nucleus and activation of canonical Wnt/β-catenin signaling, further promoting osteogenesis and inhibiting osteoclastic differentiation. In vivo, we conducted ovariectomy (OVX) to create a model of OVX-induced postmenopausal OP in mice. When analyzed by micro-CT scanning, enhancement of bone mineral density, bone volume, trabecular number, and thickness was seen in the CFZ-treated mice. Also, we noticed increased osteogenesis and decreased osteoclastogenesis, diminished expression of PSME1 and PSME2 and activated Wnt/β-catenin signaling in bone sections from OP mice treated with CFZ. Overall, our data indicated that PSME1/2 may serve as new targets for the treatment of OP, and targeting PSME1/2 with CFZ provides a candidate therapeutic molecule for postmenopausal OP.
•PSME1/2 protein levels accumulated in osteoblasts and osteoclasts in OP.•PSME1/2 inhibited osteogenesis and promoted osteoclasts formation via inhibiting Wnt/β-catenin signaling.•Carfilzomib targeting PSME1/2 to activate Wnt/β-catenin and alleviate bone loss in OP.
BackgroundThis study sought to identify potential key genes for osteosarcoma metastasis and analyze their immune infiltration patterns using bioinformatic methods. MethodsWe obtained transcriptomic ...data related to osteosarcoma and osteosarcoma with metastasis from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) and The Gene Expression Omnibus (GEO) databases and identified the differentially expressed genes (DEGs). We also identified potential key genes for osteosarcoma metastasis by a protein-protein interaction network analysis, and we conducted a Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify the core genes for prognosis, immune cell infiltration, and drug sensitivity, and the risk prediction and prognosis models of metastasis were constructed. ResultsBy comparing the transcriptome data of osteosarcomas without metastasis and those with metastasis, a total of 19 core DEGs were identified, and the GO and KEGG analyses revealed an association between these DEGs and the regulation of cell division, secretory granule lumen, the Ras-associated protein 1 (Rap1) signaling pathway, and the mitogen-activated protein kinase (MAPK) signaling pathway. Compared with other immune cells, macrophage infiltration was predominant in osteosarcoma samples with metastatic osteosarcoma, and insulin-like growth factors-1 (IGF1) and myelocytomatosis protein 2 (MYC2) genes were predicted to more than 50 targeted therapeutic agents. A metastasis prediction model with 5 genes i.e., ecotropic viral integration site 2B (EVI2B), CCAAT/enhancer binding protein (CEBPA), lymphocyte cytosolic protein 2 (LCP2), selectin L (SELL), and Niemann-Pick disease, type C2A (NPC2A), and a prognostic model with 4 genes i.e., insulin-like growth factors-2 (IGF2), cathepsin O (CTSO), Niemann-Pick disease, type C2 (NPC2), and amyloid beta (A4) precursor protein-binding, family B, member 1 interacting protein (APBB1IP) were developed. ConclusionsWe constructed a metastasis prediction model with 5 genes (i.e., EVI2B, CEBPA, LCP2, SELL, and NPC2A), and a prognostic model with 4 genes (i.e., IGF2, CTSO, NPC2, and APBB1IP) that may be potential biomarkers for osteosarcoma metastasis. Macrophages are the predominant immune infiltrating cells in osteosarcoma metastasis and may provide a new direction for the treatment of osteosarcoma.
Role of microRNA-429 (miRNA-429) in osteogenic differentiation of hADMSCs was elucidated to explore the potential mechanism. Serum level of miRNA-429 in osteoporosis patients and controls was ...determined by quantitative real-time polymerase chain reaction (qRT-PCR). After H
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induction in hADMSCs, cell viability and reactive oxygen species (ROS) level were determined by cell-counting kit (CCK-8) assay and flow cytometry, respectively. Alkaline phosphatase (ALP) activity in H
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-induced hADMSCs was also detected. The binding condition between miRNA-429 and SCD-1 was verified by dual-luciferase reporter gene assay. Relative levels of osteogenesis-related genes influenced by SCD-1 and miRNA-429 were detected by qRT-PCR. Furthermore, regulatory effects of SCD-1 and miRNA-429 on ALP activity and calcification ability of hADMSCs were evaluated. miRNA-429 was significantly upregulated in serum of osteoporosis patients. During the process of osteogenesis differentiation, H
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induction gradually upregulated miRNA-429 in hADMSCs. Overexpression of miRNA-429 markedly reduced ALP activity. Subsequent dual-luciferase reporter gene assay verified that miRNA-429 could bind to SCD-1 and negatively regulated its protein level in hADMSCs. SCD-1 was obviously downregulated in the osteogenesis differentiation of hADMSCs under oxidative stress. Moreover, silencing of SCD-1 suppressed expression of osteogenesis-related gene, ALP activity and calcification ability. Notably, SCD-1 knockdown partially reversed the regulatory effect of miRNA-429 on the osteogenic differentiation of hADMSCs. miRNA-429 suppresses the osteogenic differentiation of hADMSCs under oxidative stress via downregulating SCD-1.
The development of rapid and field monitoring tools is highly desirable for the sensitive detection of organophosphate pesticide (OP) residues in water and agriculture products without interference. ...A novel disposable acetylcholinesterase (AChE) biosensor with low detecting potential (+50mV), good selectivity, and high sensitivity was developed based on electrochemically reduced graphene oxide and Nafion hybrid nanocomposite (Er-GRO–Nafion) modified electrode. The Er-GRO–Nafion nanocomposite with conductive and three-dimensional interpenetrating network owns excellent characters as electrode modification material. It effectively promoted the electron transfer rate of electrode interface, could catalyze the anodic oxidation of thiocholine at ultra-low potential, and facilitated the access of substrates to the active centers. The modified electrode was used for the electrochemical detection of dichlorvos after adsorbing AChE on the biocompatible matrix. By dexterously controlling the electrochemical reduction variables and optimizing the electrode preparation parameters, the proposed electrochemical biosensor showed high sensitivity, wide linear range (from 5.0 to 100ngmL−1 and from 1.0 to 20μgmL−1), low detection limit (2.0ngmL−1), good stability and reproducibility. It also had high precision for the real sample analysis, which indicated the good perspective for field application.
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