ABSTRACT
Spinal cord injury (SCI) involves neuronal apoptosis and axonal disruption, leading to severe motor dysfunction. Studies indicate that exosomes transport microRNAs (miRNAs) and play a crucial role in intercellular communication. This study aimed to explore whether the bone marrow mesenchymal stem cell (BMSCs)-exosomal miR-17-92 cluster can protect against SCI and to explain the underlying mechanisms. In vivo and in vitro SCI models were established and treated with control exosomes (con-exo) or exosomes derived from BMSCs transfected with miR-17-92 cluster plasmid (miR-17-92-exo). Rat BMSCs were isolated and positive markers were identified by flow cytometry. BMSC-derived exosomes were extracted and verified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. The expression of the miR-17-92 cluster was validated by quantitative reverse transcription PCR (qRT-PCR). Spinal cord function, histopathological changes, apoptotic cells, and inflammatory cytokines release in spinal cord tissues were assessed using the Basso-Beattie-Bresnahan (BBB) score, hematoxylin and eosin (HE) staining, terminal deoxynucleotide transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR. In PC12 cells, cell proliferation, apoptosis, apoptosis-related proteins cleaved-Caspase3 expression, and inflammatory factors secretion were analyzed using a cell counting kit-8 (CCK8) assay, flow cytometry, western blotting, and ELISA. Our data revealed that the exosomes were successfully isolated from rat BMSCs. The BMSC-exosomal miR-17-92 cluster improved neural functional recovery after SCI, as evidenced by an increased BBB score, improved pathological damage, reduced neuronal apoptosis, and decreased inflammatory factors release. Additionally, miR-17-92-exo treatment significantly inhibited lipopolysaccharide (LPS)-induced reduction in cell viability, increase in cell apoptosis, and upregulation of inflammatory factors in PC12 cells. The exosomal miR-17-92 cluster derived from BMSCs improved functional recovery and exhibited neuroprotective effects in SCI by alleviating apoptosis and inflammation.
ABSTRACT
Surface treatment and bioactive metal ion incorporation are effective methods for the modification of titanium alloys to be used as biomaterials. However, few studies have demonstrated the use of air-plasma treatment in orthopedic biomaterial development. Additionally, no study has performed a direct comparison between unmodified titanium alloys and air-plasma-treated alloys with respect to their biocompatibility and osteogenesis. In this study, the biological activities of unmodified titanium alloys, air-plasma-treated titanium alloys, and air-plasma-treated strontium-doped/undoped calcium phosphate (CaP) coatings were compared. The strontium-doped CaP (Sr-CaP) coating on titanium alloys were produced by selective laser melting (SLM) technology as well as micro-arc oxidation (MAO) and air-plasma treatment. The results revealed that rapid air-plasma treatment improved the biocompatibility of titanium alloys and that Sr-CaP coating together with air-plasma treatment significantly enhanced both the biocompatibility and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Overall, this study demonstrated that low temperature air-plasma treatment is a fast and effective surface modification which improves the biocompatibility of titanium alloys. Additionally, air-plasma-treated Sr-CaP coatings have numerous practical applications and may provide researchers with new tools to assist in the development of orthopedic implants.
