Collagen sponge scaffolds loaded with Trichostatin A pretreated BMSCs-derived exosomes regulate macrophage polarization to promote skin wound healing.

The process of wound healing includes the inflammatory stage, which plays an important role. Macrophages can promote inflammatory response and also promote angiogenesis, wound contraction and tissue remodeling required for wound healing. It is crucial to promote macrophages to polarize from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype at a critical time for the quality of wound healing. Because mesenchymal stem cell-derived exosomes have broad therapeutic prospects in the field of tissue repair and regeneration, in this study, we explored whether trichostatin A pretreated bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (T-Exo) could promote wound healing by binding to biomaterial scaffolds through certain anti-inflammatory effects. In the cell experiment, we established macrophage inflammation model and then treated with T-Exo, and finally detected the expression levels of macrophage polarization proteins CD206, CD86 and TNF-α, iNOS, and Arg-1 by Western Blot and immunofluorescence staining; detected the expression levels of inflammation-related genes TNF-α, iNOS, IL-1ß, IL-10 and anti-inflammatory genes CD206 and Arg-1 by qRT-PCR; explored the promoting ability of T-Exo to promote cell migration and tube formation by cell scratch experiment and angiogenesis experiment. The results showed that T-Exo could promote the polarization of M1 macrophages to M2 macrophages, and promote the migration and angiogenesis of HUVECs. Because TSA pretreatment may bring about changes in the content and function of BMSCs-derived exosomes, proteomic analysis was performed on T-Exo and unpretreated BMSCs-derived exosomes (Exo). The results showed that the differentially expressed proteins in T-Exo were related to some pathways that promote angiogenesis, cell migration, proliferation, and re-epithelialization. Then, exosome/collagen sponge (T-Exo/Col) biological scaffolds were prepared, and the physicochemical properties and biocompatibility of the scaffolds were investigated. Animal skin wound models were established, and the therapeutic effect and anti-inflammatory effect of T-Exo/Col in wound repair were evaluated by small animal in vivo imaging, H&E staining, Masson trichrome staining, immunohistochemical staining, Western Blot, and qRT-PCR. The results showed that T-Exo significantly promoted wound healing by inhibiting inflammation, thereby further promoting angiogenesis and collagen formation in vivo. Moreover, the existence of Col scaffold in T-Exo/Col enabled T-Exo to achieve a certain sustained release effect. Finally, we further explored whether TSA exerts beneficial effects by inhibiting HDAC6 gene of BMSCs, but the results showed that knockdown of HDAC6 gene would cause oxidative stress damage to BMSCs, which means that TSA does not produce these beneficial effects by inhibiting HDAC6 gene. What molecular mechanisms TSA exerts beneficial effects through needs to be further elucidated in the future.

Advances in the Mechanistic Study of the Control of Oxidative Stress Injury by Modulating HDAC6 Activity.

Oxidative stress is defined as an injury resulting from a disturbance in the dynamic equilibrium of the redox environment due to the overproduction of active/radical oxygen exceeding the antioxidative ability of the body. This is a key step in the development of various diseases. Oxidative stress is modulated by different factors and events, including the modification of histones, which are the cores of nucleosomes. Histone modification includes acetylation and deacetylation of certain amino acid residues; this process is catalyzed by different enzymes. Histone deacetylase 6 (HDAC6) is a unique deacetylating protease that also catalyzes the deacetylation of different nonhistone substrates to regulate various physiologic processes. The intimate relationship between HDAC6 and oxidative stress has been demonstrated by different studies. The present paper aims to summarize the data obtained from a mechanistic study of HDAC6 and oxidative stress to guide further investigations on mechanistic characterization and drug development.

Research progress of extracellular vesicles and exosomes derived from mesenchymal stem cells in the treatment of oxidative stress-related diseases.

There is growing evidence that mesenchymal stem cell-derived extracellular vesicles and exosomes can significantly improve the curative effect of oxidative stress-related diseases. Mesenchymal stem cell extracellular vesicles and exosomes (MSC-EVs and MSC-Exos) are rich in bioactive molecules and have many biological regulatory functions. In this review, we describe how MSC-EVs and MSC-Exos reduce the related markers of oxidative stress and inflammation in various systemic diseases, and the molecular mechanism of MSC-EVs and MSC-Exos in treating apoptosis and vascular injury induced by oxidative stress. The results of a large number of experimental studies have shown that both local and systemic administration can effectively inhibit the oxidative stress response in diseases and promote the survival and regeneration of damaged parenchymal cells. The mRNA and miRNAs in MSC-EVs and MSC-Exos are the most important bioactive molecules in disease treatment, which can inhibit the apoptosis, necrosis and oxidative stress of lung, heart, kidney, liver, bone, skin and other cells, and promote their survive and regenerate.

Exosomes and exosome composite scaffolds in periodontal tissue engineering.

Promoting complete periodontal regeneration of damaged periodontal tissues, including dental cementum, periodontal ligament, and alveolar bone, is one of the challenges in the treatment of periodontitis. Therefore, it is urgent to explore new treatment strategies for periodontitis. Exosomes generated from stem cells are now a promising alternative to stem cell therapy, with therapeutic results comparable to those of their blast cells. It has great potential in regulating immune function, inflammation, microbiota, and tissue regeneration and has shown good effects in periodontal tissue regeneration. In addition, periodontal tissue engineering combines exosomes with biomaterial scaffolds to maximize the therapeutic advantages of exosomes. Therefore, this article reviews the progress, challenges, and prospects of exosome and exosome-loaded composite scaffolds in periodontal regeneration.

Extracellular vesicles in the treatment of oxidative stress injury: global research status and trends.

Objective: The aim of this study was to conduct a bibliometric analysis of the literature on "Extracellular Vesicles in the Treatment of Oxidative Stress Injury" and to reveal its current status, hot spots and trends. Methods: The relevant literature was obtained from the Web of Science Core Collection (WoSCC) on 29 April 2023. We performed clustering and partnership analysis of authors, institutions, countries, references and keywords in the literature through CiteSpace software and the bibliometric online analysis platform and mapped the relevant knowledge maps. Results: A total of 1,321 relevant publications were included in the bibliometric analysis, with the number of publications in this field increasing year by year. These included 944 "articles" and 377 "reviews". The maximum number of publications published in China is 512, and the maximum number of highly cited publications published in the United States is 20. Based on CiteSpace, the country collaboration network map shows close and stable collaboration among high-productivity countries. Based on WoSCC, there are 1706 relevant research institutions and 119 highly cited elite institutions, among which Kaohsing Chang Gung Men Hosp has the most extensive influence. Studies related to "Extracellular Vesicles in the Treatment of Oxidative Stress Injury" have been published in 548 journals. The keywords of the publications show the main research areas and breakthroughs. Based on WoSCC, the keywords of the research area "Extracellular Vesicles in the Treatment of Oxidative Stress Injury" were found to be as follows: exosome(s), extracellular vesicle(s), oxidative stress, inflammation, mesenchymal stem cells, apoptosis, microRNA (miRNA), mitochondria, biomarker, autophagy, angiogenesis and Alzheimer's disease. Analysis showed that "mesenchymal stem cells", "microRNA", "autophagy", "histology" and "therapeutic" emerged as highly explosive keywords. Conclusion: This study is the first to use visual software and data mining to assess the literature in the field of "Extracellular Vesicles in the Treatment of Oxidative Stress Injury". The research history, research status and direction in this field provide a theoretical basis for its scientific research.