Injectable Self-Healing Antibacterial Hydrogels with Tailored Functions by Loading Peptide Nanofiber-Biomimetic Silver Nanoparticles.

Polymer hydrogels find extensive application in biomedicine, serving specific purposes such as drug delivery, biosensing, bioimaging, cancer therapy, tissue engineering, and others. In response to the growing threat of bacterial infections and the escalating resistance to conventional antibiotics, this research introduces a novel injectable, self-healing antimicrobial hydrogel comprising bioactive aldolized hyaluronic acid (AHA) and quaternized chitosan (QCS). This designed QCS/AHA hydrogel incorporates self-assembling peptide nanofibers (PNFs) and small-sized silver nanoparticles (AgNPs) for tailored functionality. The resulting hybrid QCS/AHA/PNF/AgNPs hydrogel demonstrates impressive rheological characteristics, broad-spectrum antimicrobial efficacy, and high biocompatibility. Notably, its antimicrobial effectiveness against Escherichia coli and S. aureus surpasses 99.9%, underscoring its potential for treating infectious wounds. Moreover, the rheological analysis confirms its excellent shear-thinning and self-healing properties, enabling it to conform closely to irregular wound surfaces. Furthermore, the cytotoxicity assessment reveals its compatibility with human umbilical vein endothelial cells, exhibiting no significant adverse effects. The combined attributes of this bioactive QCS/AHA/PNF/AgNPs hydrogel position it as a promising candidate for antimicrobial applications and wound healing.

M2 macrophage-derived exosomal miR-486-5p influences the differentiation potential of bone marrow mesenchymal stem cells and osteoporosis.

BACKGROUND: An imbalance between osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMMSCs) can cause osteoporosis. Macrophage-derived exosomes (MD-Exos) and microRNAs (miRNAs) enriched in exosomes participate in the differentiation of BMMSCs. METHODS: Bioinformatics methods were used to analyze differentially expressed miRNAs. We cocultured M2 macrophages and BMMSCs to examine the biological function of exosomal microRNA-486-5p (miR-486-5p) on BMMSCs differentiation. Gain-of-function experiments related to osteogenesis were designed to investigate the effects of exosomes carrying miR-486-5p on an ovariectomized (OVX) mice model and the direct impact of miR-486-5p on BMMSCs. A dual luciferase experiment was performed to demonstrate the target gene of miR-486-5p. RESULTS: Bioinformatics analysis identified high expression of miRNA-486 in M2 macrophage-derived exosomes (M2D-Exos). The in vitro results demonstrated that M2 macrophage-derived exosomal miR-486-5p enhanced osteogenic capacity but inhibited the adipogenesis of BMMSCs. The direct effect of miR-486-5p on BMMSCs showed the same effects. Animal experiments revealed that exosomal miR-486-5p rescued bone loss of OVX mice. SMAD2 was characterized as a target gene of miR-486-5p. Pathway analysis showed that M2 macrophage-derived exosomal miR-486-5p stimulated osteogenic differentiation via the TGF-ß/SMAD2 signalling pathway. CONCLUSIONS: Taken together, M2 macrophage-derived exosomal miR-486-5p influences the differentiation potential of BMMSCs through the miR-486-5p/SMAD2/TGF-ß signalling pathway and osteoporosis.

Ortho-silicic Acid Plays a Protective Role in Glucocorticoid-Induced Osteoporosis via the Akt/Bad Signal Pathway In Vitro and In Vivo.

Glucocorticoid-induced osteoporosis (GIOP) has been the most common form of secondary osteoporosis. Glucocorticoids (GCs) can induce osteocyte and osteoblast apoptosis. Plenty of research has verified that silicon intake would positively affect bone. However, the effects of silicon on GIOP are not investigated. In this study, we assessed the impact of ortho-silicic acid (OSA) on Dex-induced apoptosis of osteocytes by cell apoptosis assays. The apoptosis-related genes, cleaved-caspase-3, Bcl-2, and Bax, were detected by western blotting. Then, we evaluated the possible role of OSA on osteogenesis and osteoclastogenesis with Dex using Alizarin red staining and tartrate-resistant acid phosphatase (TRAP) staining. We also detected the related genes by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting. We then established the GIOP mouse model to evaluate the potential role of OSA in vivo. We found that OSA showed no cytotoxic on osteocytes below 50 µM and prevented MLO-Y4 from Dex-induced apoptosis. We also found that OSA promoted osteogenesis and inhibited osteoclastogenesis with Dex. OSA had a protective effect on GIOP mice via the Akt signal pathway in vivo. In the end, we verified the Akt/Bad signal pathway in vitro, which showed the same results. Our finding demonstrated that OSA could protect osteocytes from apoptosis induced by GCs both in vitro and in vivo. Also, it promoted osteogenesis and inhibited osteoclastogenesis with the exitance of Dex. In conclusion, OSA has the potential value as a therapeutic agent for GIOP.

Exosomal MiR-199a-5p Inhibits Tumorigenesis and Angiogenesis by Targeting VEGFA in Osteosarcoma.

Background: Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents. microRNAs have been found to play a vital role in tumor angiogenesis. Here, we investigated the effects of miR-199a-5p on tumor growth and angiogenesis in osteosarcoma. Furthermore, the underlying molecular mechanisms and signaling pathways were explored. Methods: The datasets were extracted from the Gene Expression Omnibus and the differentially expressed miRNAs (DEmiRNAs) were screened out by the GEO2R online platform. The potential target genes were predicted using the miRTarBase database. The predicted target genes were further analyzed by Gene Ontology and pathway enrichment analysis and a regulatory network of DEmiRNAs and their target genes was constructed. In addition, the effects of osteosarcoma cell derived exosomal miR-199a-5p on the proliferation, migration and neovascularization of HUVECs were evaluated by conducting EdU assays, Transwell experiments and tube formation assays. A dual-luciferase reporter assay was performed to detect whether VEGFA was the direct target of miR-199a-5p. Furthermore, in vivo xenograft models were established to further investigate the intrinsic role of miR-199a-5p in osteosarcoma tumorigenesis and angiogenesis. Results: A total of 149 DE-miRNAs were screened out, including 136 upregulated miRNAs and 13 downregulated miRNAs in human osteosarcoma plasma samples compared with normal plasma samples. A total of 1313 target genes of the top three upregulated and downregulated miRNAs were predicted. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and VEGFA. By constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-663a, miR-199a-5p and miR-223-3p. In addition, we found that the expression level of miR-199a-5p in exosomes derived from osteosarcoma cells was remarkably higher than the osteosarcoma cells, and the exosomes derived from osteosarcoma cells were transported to HUVECs. Overexpression of miR-199a-5p could significantly inhibited HUVEC proliferation, migration and neovascularization, whereas downregulation of miR-199a-5p expression exerted the opposite effect. Moreover, the in vivo results verified that overexpression of miR-199a-5p in osteosarcoma cells could suppress the growth and angiogenesis of tumors. Conclusion: Our results demonstrated that miR-199a-5p could be transported from osteosarcoma cells to HUVECs through exosomes, subsequently targeting VEGFA and inhibiting the growth and angiogenesis of osteosarcoma. Therefore, miR-199a-5p may act as a biomarker in the diagnosis and treatment of osteosarcoma.

Using EMG signals to assess proximity of instruments to nerve roots during robot-assisted spinal surgery.

BACKGROUND: Detecting neural threats using electromyography (EMG) has gained recognition in the field of spinal surgery. To provide an efficient approach to detect neural threats during the operation of the spinal surgery robot, an automated method based the internal connection between EMG signal and neural proximity (NP) was explored by experiments. METHODS: A NP classifier was designed to distinguish the pattern of the threats. Then, it was evaluated in rabbit models in vivo. The experiments were conducted using 20 rabbits. In each rabbit, two puncture paths were created using a surgical robot. For each path, EMG signals were recorded at series of path-points with different neural proximities, and were constructed as datasets after data cleaning and processing. The proposed NP classifier was trained and tested on the datasets. RESULTS: Classification accuracy of Path 1 and Path 2 were 99.1% and 94.0%, respectively. CONCLUSION: This feasibility study proved that EMG can be used to detect the proximity of surgical instruments to nerve roots during robot-assisted spinal surgery. As the methods of detecting neural threats for surgical robots are still scarce, we believe this work will improve the clinical performance of spinal surgery robots and help the doctors to perform surgery safely.