Regenerative Biomaterials最新文献

Endothelial cell proliferation plays an important role in angiogenesis and treatment of related diseases. The aim of this study was to evaluate the effect of polyethylenimine (PEI)-modified graphene quantum dots (GQDs) gene vectors on endothelial cell proliferation. The GQDs-cationic polymer gene vectors were synthesized by amidation reaction, and used to deliver pZNF580 gene to Human umbilical vein endothelial cells (HUVECs) for promoting their proliferation. The chemical modification of GQDs can adjust gene vectors' surface properties and charge distribution, thereby enhancing their interaction with gene molecules, which could effectively compress the pZNF580 gene. The CCK-8 assay showed that the cell viability was higher than 80% at higher vector concentration (40 μg/mL), demonstrating that the GQDs-cationic polymer gene vectors and their gene complex nanoparticles (NPs) having low cytotoxicity. The results of the live/dead cell double staining assay were consistent with those of the CCK-8 assay, in which the cell viability of the A-GQDs/pZNF580 (94.38 ± 6.39%), C-GQDs-PEI- polylactic acid-co-polyacetic acid (PLGA)/pZNF580 (98.65 ± 6.60%) and N-GQDs-PEI-PLGA/pZNF580 (90.08 ± 1.60%) groups was significantly higher than that of the Lipofectamine 2000/pZNF580 (71.98 ± 3.53%) positive treatment group. The results of transfection and western blot experiments showed that the vector significantly enhanced the delivery of plasmid to HUVECs and increased the expression of pZNF580 in HUVECs. In addition, the gene NPs better promote endothelial cell migration and proliferation. The cell migration rate and proliferation ability of C-GQDs-PEI-PLGA/pZNF580 and N-GQDs-PEI-PLGA/pZNF580 treatment groups were higher than those of Lipofectamine 2000/pDNA treatment group. Modified GQDs possess the potential to serve as efficient gene carriers. They tightly bind gene molecules through charge and other non-covalent interactions, significantly improving the efficiency of gene delivery and ensuring the smooth release of genes within the cell. This innovative strategy provides a powerful means to promote endothelial cell proliferation.

Cartilage defects may lead to severe degenerative joint diseases. Tissue engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage repair. However, the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully clarified. Herein, we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced chondrogenesis. Results showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the TGF-β signaling pathway, and integrin-β1 (ITGB1), a receptor of collagen, was highly expressed in bone marrow mesenchymal stem cells (BMSCs). Further analysis showed genes such as COL2A1 and Tenascin C (TNC) that interacted with ITGB1 were significantly enriched in extracellular matrix (ECM) structural constituents in the chondrogenic induction group. Knockdown of ITGB1 led to the downregulation of cartilage-specific genes (SOX9, ACAN, COL2A1), SMAD2 and TNC, as well as the downregulation of phosphorylation of SMAD2/3. Knockdown of TNC also resulted in the decrease of cartilage markers, ITGB1 and the SMAD2/3 phosphorylation but overexpression of TNC showed the opposite trend. Finally, in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage regeneration. In summary, we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen hydrogel. It can activate TGF-SMAD2/3 signaling, followed by impacting TNC expression, which in turn promotes the interaction of ITGB1 and TGF-SMAD2/3 signaling to enhance chondrogenesis. These may provide concernful support for cartilage tissue engineering and biomaterials development.

In the bone immune microenvironment, immune cells can regulate osteoblasts through a complex communication network. Macrophages play a central role in mediating immune osteogenesis, exosomes derived from them have osteogenic regulation and can be used as carriers in bone tissue engineering. However, there are problems with exosomal therapy alone, such as poor targeting, and the content of loaded molecules cannot reach the therapeutic concentration. In this study, macrophage-derived exosomes modified with miR-365-2-5p were developed to accelerate bone healing. MC3T3-E1 cells were incubated with the culture supernatants of M0, M1 and M2 macrophages, and it was found that the culture medium of M2 macrophages had the most significant effects in contributing to osteogenesis. High-throughput sequencing identified that miR-365-2-5p was significantly expressed in exosomes derived from M2 macrophages. We incubated MC3T3-E1 with exosomes overexpressing or knocking down miR-365-2-5p to examine the biological function of exosome miR-365-2-5p on MC3T3-E1 differentiation. These findings suggested that miR-365-2-5p secreted by exosomes increased the osteogenesis of MC3T3-E1. Moreover, miR-365-2-5p had a direct influence over osteogenesis for MC3T3-E1. Sequencing analysis combined with dual luciferase detection indicated that miR-365-2-5p binded to the 3'-UTR of OLFML1. In summary, exosomes secreted by M2 macrophages targeted OLFML1 through miR-365-2-5p to facilitate osteogenesis.

Increasing studies have revealed the importance of mechanical cues in tumor progression, invasiveness and drug resistance. During malignant transformation, changes manifest in either the mechanical properties of the tissue or the cellular ability to sense and respond to mechanical signals. The major focus of the review is the subtle correlation between mechanical cues and apoptosis in tumor cells from a mechanobiology perspective. To begin, we focus on the intracellular force, examining the mechanical properties of the cell interior, and outlining the role that the cytoskeleton and intracellular organelle-mediated intracellular forces play in tumor cell apoptosis. This article also elucidates the mechanisms by which extracellular forces guide tumor cell mechanosensing, ultimately triggering the activation of the mechanotransduction pathway and impacting tumor cell apoptosis. Finally, a comprehensive examination of the present status of the design and development of anti-cancer materials targeting mechanotransduction is presented, emphasizing the underlying design principles. Furthermore, the article underscores the need to address several unresolved inquiries to enhance our comprehension of cancer therapeutics that target mechanotransduction.

Eradicating biofouling from implant surfaces is essential in treating peri-implant infections, as it directly addresses the microbial source for infection and inflammation around dental implants. This controlled laboratory study examines the effectiveness of the four commercially available debridement solutions '(EDTA (Prefgel^®), NaOCl (Perisolv^®), H₂O₂ (Sigma-Aldrich) and Chlorhexidine (GUM^® Paroex^®))' in removing the acquired pellicle, preventing pellicle re-formation and removing of a multi-species oral biofilm growing on a titanium implant surface, and compare the results with the effect of a novel formulation of a peroxide-activated 'Poloxamer gel (Nubone^® Clean)'. Evaluation of pellicle removal and re-formation was conducted using scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy to assess the surface morphology, elemental composition and chemical surface composition. Hydrophilicity was assessed through contact angle measurements. The multi-species biofilm model included Streptococcus oralis, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans, reflecting the natural oral microbiome's complexity. Biofilm biomass was quantified using safranin staining, biofilm viability was evaluated using confocal laser scanning microscopy, and SEM was used for morphological analyses of the biofilm. Results indicated that while no single agent completely eradicated the biofilm, the 'Poloxamer gel' activated with 'H₂O₂' exhibited promising results. It minimized re-contamination of the pellicle by significantly lowering the contact angle, indicating enhanced hydrophilicity. This combination also showed a notable reduction in carbon contaminants, suggesting the effective removal of organic residues from the titanium surface, in addition to effectively reducing viable bacterial counts. In conclusion, the 'Poloxamer gel + H₂O₂' combination emerged as a promising chemical decontamination strategy for peri-implant diseases. It underlines the importance of tailoring treatment methods to the unique microbial challenges in peri-implant diseases and the necessity of combining chemical decontaminating strategies with established mechanical cleaning procedures for optimal management of peri-implant diseases.

Bioprosthetic heart valve (BHV) replacement has been the predominant treatment for severe heart valve diseases over decades. Most clinically available BHVs are crosslinked by glutaraldehyde (GLUT), while the high toxicity of residual GLUT could initiate calcification, severe thrombosis, and delayed endothelialization. Here, we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of BHVs. In particular, recombinant humanized collagen type III (rhCOLIII), which was precisely customized with anti-coagulant and pro-endothelialization bioactivity, was first incorporated into the polyvinyl alcohol (PVA)-based hydrogel via hydrogen bond interactions. Then, tannic acid was introduced to enhance the mechanical performance of PVA-based hydrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of substrates. In vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLIII and TA possessed long-term anti-coagulant, accelerated endothelialization, mild inflammatory response and anti-calcification properties. Therefore, our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.

Tendinopathy is a common disorder that causes local dysfunction and reduces quality of life. Recent research has indicated that alterations in the inflammatory microenvironment play a vital role in the pathogenesis of tendinopathy. Herein, injectable methacrylate gelatin (GelMA) microspheres (GM) were fabricated and loaded with heparin-dopamine conjugate (HDC) and hepatocyte growth factor (HGF). GM@HDC@HGF were designed to balance the inflammatory microenvironment by inhibiting oxidative stress and inflammation, thereby regulating extracellular matrix (ECM) metabolism and halting tendon degeneration. Combining growth factors with heparin was expected to improve the encapsulation rate and maintain the long-term efficacy of HGF. In addition, the catechol groups on dopamine have adhesion and antioxidant properties, allowing potential attachment at the injured site, and better function synergized with HGF. GM@HDC@HGF injected in situ in rat Achilles tendinopathy (AT) models significantly down-regulated oxidative stress and inflammation, and ameliorated ECM degradation. In conclusion, the multifunctional platform developed presents a promising alternative for the treatment of tendinopathy.