Fermented Coix seed hydrolysate upregulates skin barrier genes and promotes wound healing

Research on traditional Chinese medicine as an effective drug for promoting wound healing

Hydrogen sulfide (H2S) as an endogenous gasotransmitter plays a critical role in promotion of wound healing. However, the current H2S release system lacks the in situ monitoring ability, which may lead to insufficient or overdose release of H2S and serious side effects. Herein, we develop a self-monitoring theranostic probe TPATCF-S, which can quickly release H2S under water stimuli associated with a self-monitoring ability by a color change from colorless to deep blue. With a full thickness dermal defect as a model, the TPATCF-S absorbed on alginate dressings can be used for wound exudate-responsive release of H2S to efficiently promote skin wound healing.

Intravenously Injected Human Fibroblasts Home to Skin Wounds, Deliver Type VII Collagen, and Promote Wound Healing

Wound healing is a complex process that requires the participation of multiple cells and cytokines. During the process of wound healing, abnormality in any stage of the process may lead to the development of a chronic refractory wound. Research has confirmed that various stem cells can promote wound healing, but some stem cells are limited in clinical application due to difficulties in isolation, susceptibility to apoptosis, ethical and legal issues. Oral mucosal stem cells (OMSCs) can avoid the above problems. This type of stem cells has the characteristics of embryonic stem cells, immune regulatory ability, and strong homogeneity. It plays an important role in the process of scarless oral wound healing, and has become a research hotspot in promoting wound healing and reducing scar formation. This article reviews the research on the mechanism, clinical application prospects, and current problems of OMSCs in promoting wound healing.

BackgroundsMinor salivary gland mesenchymal stem cells (MSGMSCs) can be easily extracted and have a broad range of sources. Applying exosomes to wounds is a highly promising method for promoting wound healing. Exosomes derived from different stem cell types have been proven to enhance wound healing, with adipose-derived stem cell (ADSC)-derived exosomes being the most extensively researched. Considering that MSGMSCs have advantages such as easier extraction compared to ADSCs, MSGMSCs should also be a very promising type of stem cell in exosome therapy. However, whether MSGMSC-derived exosomes (MSGMSC-exos) can promote wound healing and how they compare to ADSC-derived exosomes (ADSC-exos) in the wound healing process remain unclear.MaterialsThe effects of MSGMSC-exos and ADSC-exos on angiogenesis in wound healing were investigated in vitro using CCK-8, scratch assays, and tube formation assays. Subsequently, the promotion of wound healing by MSGMSC-exos and ADSC-exos was evaluated in vivo using a full-thickness wound defect model in mice. Immunohistochemistry was used to verify the effects of MSGMSC-exos and ADSC-exos on promoting collagen deposition, angiogenesis, and cell proliferation in the wound. Immunofluorescence staining was performed to investigate the role of MSGMSC-exos and ADSC-exos in modulating the inflammatory response in the wound. Furthermore, proteomic sequencing was conducted to investigate the functional similarities and differences between the proteomes of MSGMSC-exos and ADSC-exos, with key protein contents verified by ELISA.ResultsMSGMSC-exos exhibited similar effects as ADSC-exos in promoting the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, with a comparable dose-dependent effect. In vivo experiments confirmed that MSGMSC-exos have similar wound healing-promoting functions as ADSC-exos. MSGMSC-exos promoted the neovascularization and maturation of blood vessels in vivo at a level comparable to ADSC-exos. Despite MSGMSC-exos showing less collagen deposition than ADSC-exos, they exhibited stronger anti-scar formation and anti-inflammatory effects. Proteomic analysis revealed that the proteins promoting wound healing in both MSGMSC-exos and ADSC-exos were relatively conserved, with ITGB1 identified as a critical protein for angiogenesis. Further differential analysis revealed that the functions specifically enriched in MSGMSC-exos and ADSC-exos reflected the functions of their source tissue.ConclusionsOur study confirms that MSGMSC-exos exhibit highly similar wound healing and angiogenesis-promoting functions compared to ADSC-exos, and the proteins involved in promoting wound healing in both are relatively conserved. Moreover, MSGMSC-exos show stronger anti-scar formation and anti-inflammatory effects than ADSC-exos. This suggests that MSGMSCs are a promising stem cell source with broad applications in wound healing treatment.

At present, current stimulation, ultra-sound, and light therapy have become effective methods to promote wound healing. Among them, infrared light is the most widely used method and is one of the important methods to promote wound healing. The therapeutic effect of infrared light on wounds is related to the effect of photobiomodulation on cells and molecules on the skin surface, but the mechanism by which photobiomodulation of infrared light promotes wound healing has not been fully elucidated. Therefore, it is necessary to study the action characteristics and the mechanism of photo-biomodulation of infrared light in promoting wound healing. This article reviews the effect of different types of infrared light on wound healing and the mechanism of infrared light in promoting wound healing.

Wound healing is a complex process with significant economic implications. Hyaluronic acid (HA), valued for its adaptability and biocompatibility, shows the potential to improve multiple facets of wound healing. Despite the expanding literature on the use of HA in wound care, a comprehensive analysis of its scholarly evolution is lacking. This study employs a bibliometric approach to objectively evaluate trends in scholarly publications regarding HA's role in promoting wound healing. We searched in the Web of Science Core Collection (WoSCC) for articles published from January 1, 2000 to March 31, 2024. We extracted relevant information about using HA to promote wound healing following a thorough screening process. Subsequently, a comprehensive analysis was undertaken on a total of 1886 publications. The analysis utilized GraphPad Prism 9, CiteSpace6.1.6, VOSviewer1.6.19, the Online Analysis Platform of Literature Metrology (http://bibliometric.com/), GeneMANIA (https://genemania.org/), and Metascape (https://metascape.org/gp/index.html#/main/step1). We retrieved 2424 publications on hyaluronic acid (HA) and wound healing from the Web of Science Core Collection, covering the period from January 2000 to March 2024, and selected 1886 for analysis. The results show a significant increase in publications since 2016, reflecting a growing focus on this field. Currently, China's publication volume has surpassed the United States since 2017, indicating a significant rise in China's influence in this area. Using CiteSpace software for co-citation analysis, we identified eight main research clusters, including promoted wound healing, injured tissue, and advanced multi-targeted composite biomaterial. Key research areas involve the role and mechanisms of hyaluronic acid in tissue repair, particularly its applications in growth factor production and regenerative therapy. Analyzing keyword co-occurrence and burst data with VOSviewer, we identified research hotspots focused on biomaterials, such as nanoparticles and hydrogels, and their antibacterial properties. The keyword "CD44" showed a long burst period, while "antibacterial" had the highest burst intensity in 2022. We identified the top 21 genes extensively studied in hyaluronic acid and wound healing, including CD44, VEGF, and TGF-β. These genes are mainly involved in regulating cell migration, adhesion, proliferation, and cytokine activity. GO enrichment and KEGG pathway analyses indicate that these genes are associated with key signaling pathways, such as MAPK and EGFR, revealing the primary mechanisms hyaluronic acid promotes wound healing. This pioneering study provides the first comprehensive bibliometric analysis of HA in wound healing. Covering the period from January 1, 2000 to March 31, 2024, it reveals a significant expansion in annual scholarly production. Current research emphasizes the development of HA-based biomaterials for enhancing wound healing.

Wound healing is a complex physiological process for maintaining skin integrity after a wound. Bone marrow-derived mesenchymal stem cells (BMSCs) are excellent cellular candidates for wound healing, which could be enhanced by exogenous stimulation. We aimed to explore the role of δ-Tocotrienol (δ-TT) in BMSC ability of wound healing. Firstly, transcriptome and single-cell analysis were used to explore the genes and pathways related to ferroptosis in wound tissues. In vitro, cell proliferation, migration, and angiogenesis of δ-TT-BMSCs were detected. In addition, qRT-PCR and immunofluorescence (IF) were applied for observing the promoting wound healing ability of δ-TT-BMSC conditioned medium (CM) on NIH-3T3 and PAM-212 cells. The level of ferroptosis was determined by the mitochondrial membrane potential and total/lipid reactive oxygen species (ROS) in the cells and the morphological changes of mitochondria were observed by transmission electron microscope. The BTB and CNC homology 1 (BACH1) expression and activation of the PI3K/AKT signaling pathway were detected by IF and western blot (WB). The effect of δ-TT-BMSCs on wound healing was observed in vivo. The regulatory mechanism of δ-TT-BMSCs on ferroptosis was verified by IHC and IF staining. In vitro, δ-TT-BMSCs declined the level of lipid ROS in NIH-3T3 and PAM-212 cells and enhanced mitochondrial membrane potential. In vivo, δ-TT-BMSCs promoted wound healing in mice by decreasing ferroptosis. In terms of mechanism, δ-TT-BMSCs inhibited the expression of BACH1 and activated PI3K/AKT signaling pathway. This study demonstrated the ability of δ-TT-BMSCs to promote wound healing by inhibiting BACH1-related ferroptosis. In addition, PI3K/AKT signaling pathway was activated by δ-TT-BMSCs and could be involved in wound healing. δ-TT-BMSCs might be a promising strategy for treating wounds.

This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments. ASC density was decreased in diabetic rats. The generation time of ASC-rich cells from diabetic rats (d-ASC-rich cells) was longer than that of ASC-rich cells from non-diabetic rats. The number of pre-apoptotic cells in the third generation (passage 3) of d-ASC-rich cells was higher than that among the ASC-rich cells from non-diabetic rats. CD31 and CD34 expression was higher in d-ASC-rich cells than in ASC-rich cells from non-diabetic rats, whereas CD44 and CD105 expression was lower than that in ASC-rich cells from non-diabetic rats. Transplantation of ASC-rich cells from non-diabetic rats promoted wound healing in both non-diabetic and diabetic rats. In contrast, d-ASC-rich cells and enriched nuclear cells only promoted wound healing in non-diabetic rats. ASC-rich cell transplantation promoted greater tissue regeneration than d-ASC-rich cell transplantation. ASC-rich cells promoted wound healing in diabetic and non-diabetic rats. ASC density was lower in the adipose tissue of diabetic rats compared with non-diabetic rats. d-ASC-rich cells did not promote wound healing in diabetic rats, suggesting that caution is warranted regarding the clinical use of diabetic adipose stem cell transplantation for the treatment of diabetic wounds.

Wound infections may disrupt the normal wound-healing process. Large amounts of antibiotics are frequently used to prevent pathogenic infections; however, this can lead to resistance development. Biomaterials possessing antimicrobial properties have promising applications for reducing antibiotic usage and promoting wound healing. Silk sericin (SS) has been increasingly explored for skin wound healing applications owing to its excellent biocompatibility and antioxidant, antimicrobial, and ultraviolet-resistant properties. In recent years, SS-based composite biomaterials with a broader antimicrobial spectrum have been extensively investigated and demonstrated favorable efficacy in promoting wound healing. This review summarizes various antimicrobial agents, including metal nanoparticles, natural extracts, and antibiotics, that have been incorporated into SS composites for wound healing and elucidates their mechanisms of action. It has been revealed that SS-based biomaterials can achieve sustained antimicrobial activity by slow-release-loaded antimicrobial agents. The antimicrobial-loaded SS composites may promote wound healing through anti-infection, anti-inflammation, hemostasis, angiogenesis, and collagen deposition. The manufacturing methods, benefits, and limitations of antimicrobial-loaded SS materials are briefly discussed. This review aims to enhance the understanding of new advances and directions in SS-based antimicrobial composites and guide future biomedical research.

Injectable hydrogels for Fenton-like Mn2+/Fe2+ delivery with enhanced chemodynamic therapy prevent osteosarcoma recurrence and promote wound healing after excision surgery

BackgroundThe shell of Haliotis diversicolor, or shijueming (SJM), is a type of traditional Chinese medicine. The SJM has appeared in historical records as early as the third and fourth centuries. Historical records have revealed that SJM had mainly been used to treat eye diseases. After the Qing Dynasty (1757), records had emerged, detailing the use of SJM for treating skin injuries, particularly for treating poorly managed ulcers or traumatic wounds. Furthermore, in our anti-inflammation-screening system, SJM significantly inhibited the expression of pro-inflammatory proteins. Previous studies have yet to adopt an animal model to verify the phenomenon and described in the historical records regarding the efficacy of SJM in promoting wound healing. Besides, the mechanism of wound healing effect of SJM is also not clear.MethodsThis study applied in vitro and in vivo models, tissue section analysis, and western blotting to evaluate the effect of SJM on wound healing. The RAW 264.7 cells were used in anti-inflammatory activity assay and phagocytic assay. Male Wistar rats were used to evaluate the effect of SJM on burn injury healing. A copper block (2 × 2 cm, 150 g) preheated to 165 °C in a dry bath was used to contact the skin area for 10 s, thus creating a full-thickness burn injury. The results were analyzed by hematoxylin and eosin staining, picrosirius red staining and Western blotting.ResultsThe results revealed that in the in vitro model, the presence of SJM decreased the inducible nitric oxide synthase (iNOS) expression and enhanced the functions of macrophages. The results of the rat burn injury model revealed that SJM decreased neutrophil infiltration, promoted wound healing, thus increasing the collagen I content and promoting the expression of transforming growth factor-beta 1 (TGF-β1) protein. We speculate that the effect and mechanism of SJM on promoting wound healing is related to macrophage activation. In the inflammation phase, SJM alleviates inflammation by inhibiting iNOS expression and removing neutrophils through phagocytosis. Furthermore, SJM induces the secretion of TGF-β1, converting collagen during the tissue remodeling phase.ConclusionsAccording to our review of relevant literature, this is the first study that applied an evidence-based method to verify that SJM alleviates inflammation, enhances phagocytosis, and triggers wound healing after burn injury. The study findings reveal that SJM provides a promising therapeutic option for treating burn injury.

Background Dragon's blood is a natural medicine with hemostatic and blood-activating effects and is used to promote wound healing. Dracorhodin perchlorate (DP) is a stable form of dracarhod and is used as a substitute for cochinchinenin. DP promotes the proliferation of rat fibroblasts and promotes wound healing in rats. Methods DP ointment (0.2 mg/mL) was applied to the skin wounds of nondiabetic and diabetic rats, and the skin of the wound was collected. Wound healing rate, H&E staining, Masson staining, TLR4 pathway, related inflammatory factors, nitric oxide synthase, and so forth were detected. Results DP treatment alleviated the prolonged inflammatory cell infiltration time and the increase in the TLR4 pathway and inflammatory factors caused by diabetes. DP also promoted wound healing by increasing eNOS protein expression and NO content in the later stage of wound healing. Conclusion DP promotes wound healing in diabetic rats by regulating the TLR4 pathway and related inflammatory factors. Therefore, adjuvant treatment of DP can be developed for diabetic wound healing.

Diabetes is a chronic metabolic disease with a high prevalence worldwide, which typically delays or impairs wound healing, potentially causing death. Low-frequency ultrasound treatment promotes the repair of various injuries and may promote wound healing. The aim of the present study was to determine whether low-frequency ultrasound can accelerate wound healing, as well as investigate its effects on the expression of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in diabetic rats. A total of 45 Wistar rats were intraperitoneally injected with 1% streptozocin following intraperitoneal injection of pentobarbital sodium anesthesia. Subsequently an incision wound was created in the skin of back. The area of the wound was recorded to calculate the rate of wound healing. The expression of VEGF and TGF-β1 was determined via immunohistochemical analysis and their mRNA and protein levels were measured via reverse transcription-quantitative PCR analysis. The results revealed that when compared with the control group, low-frequency ultrasound treatment significantly increased wound healing rate in diabetic rats and markedly increased the mRNA and protein levels of VEGF and TGF-β1. US treatment also reduced the mRNA and protein levels of TNF-α and IL-6. In conclusion, the results of the present study indicated that low-frequency ultrasound promotes the expression of VEGF and TGF-β1, and inhibits the expression of IL-6 and TNF-α, thereby promoting wound healing in diabetic rats.

Huangbai liniment and berberine promoted wound healing in high-fat diet/Streptozotocin-induced diabetic rats.