Migration Of Human Skin Fibroblasts Research Articles

Research on the TSPAN6 regulating the secretion of ADSCs-Exos through syntenin-1 and promoting wound healing.

Exosomes (Exos) from adipose-derived stem cells (ADSCs) have a high inclusion content and low immunogenicity, which helps to control inflammation and accelerate the healing of wounds. Unfortunately, the yield of exosomes is poor, which raises the expense and lengthens the treatment period in addition to impairing exosomes' therapeutic impact. Thus, one of the key problems that needs to be resolved in the current exosome study is increasing the exosome yield. Tetraspanin-6 (TSPAN6) overexpression and knockdown models of ADSCs were constructed to determine the number of exosomes secreted by each group of cells as well as the number of multivesicular bodies (MVBs) and intraluminal vesicles (ILVs) within the cells. Subsequently, the binding region of the interaction between TSPAN6 and syntenin-1 was identified using the yeast two-hybrid assay, and the interaction itself was identified by immunoprecipitation. Finally, cellular and animal studies were conducted to investigate the role of each class of exosomes. When compared to the control group, the number of intracellular MVBs and ILVs was significantly larger, and the number of ADSCsTSPAN6+-Exos was more than three times higher. However, TSPAN6's ability to stimulate exosome secretion was reduced as a result of syntenin-1 knockdown. Additional yeast two-hybrid assay demonstrated that the critical structures for their interaction were the N-terminal, Postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ1), and PDZ2 domains of syntenin-1, and the C-terminal of TSPAN6. In animal trials, the wound healing rate was best in the ADSCsTSPAN6+-Exos group, while cellular experiments demonstrated that ADSCsTSPAN6+-Exos better enhanced the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs). TSPAN6 stimulates exosome secretion and formation, as well as the creation of MVBs and ILVs in ADSCs. Syntenin-1 is essential for TSPAN6's stimulation of ADSCs-Exos secretion. Furthermore, ADSCsTSPAN6+-Exos has a greater ability to support wound healing, angiogenesis, and the proliferation and migration of a variety of cells.

MSC Exosomes Containing Valproic Acid Promote Wound Healing by Modulating Inflammation and Angiogenesis.

Chronic wounds that are difficult to heal pose a major challenge for clinicians and researchers. Currently, common treatment methods focus on isolating the wound from the outside world, relying on the tissue at the wound site to grow and heal unaided. Umbilical cord mesenchymal stem cell (MSC) exosomes can promote wound healing by enhancing new blood vessel growth at the wound site. Valproic acid (VPA) reduces the inflammatory response and acts on macrophages to accelerate wound closure. In this study, VPA was loaded into umbilical cord MSC exosomes to form a drug carrier exosome (VPA-EXO) with the aim of investigating the effect of VPA-EXO on wound healing. This study first isolated and obtained umbilical cord MSC exosomes, then added VPA to the exosomes and explored the ability of VPA-EXO to promote the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs), as well as the ability to promote the angiogenesis of HUVECs, by using scratch, Transwell, and angiogenesis assays. An in vitro cell model was established and treated with VPA-EXO, and the expression levels of inflammation and pro-angiogenesis-related proteins and genes were examined using Western blot and qRT-PCR. The therapeutic effect of VPA-EXO on promoting wound healing in a whole skin wound model was investigated using image analysis of the wound site, H&E staining, and immunohistochemical staining experiments in a mouse wound model. The in vitro model showed that VPA-EXO effectively promoted the proliferation and migration of human skin fibroblast cells and human umbilical vein endothelial cells; significantly inhibited the expression of MMP-9, IL-1β, IL-8, TNF-α, and PG-E2; and promoted the expression of vascular endothelial growth factors. In the mouse wound model, VPA-EXO reduced inflammation at the wound site, accelerated wound healing, and significantly increased the collagen content of tissue at the wound site. As a complex with dual efficacy in simultaneously promoting tissue regeneration and inhibiting inflammation, VPA-EXO has potential applications in tissue wound healing and vascular regeneration. In future studies, we will further investigate the mechanism of action and application scenarios of drug-loaded exosome complexes in different types of wound healing and vascular regeneration.

Exploring the potential mechanisms of the ethyl acetate fraction of Hippophae rhamnoides L. seeds as a natural healing agent for wound repair

Ethnopharmacological relevanceSea buckthorn (Hippophae rhamnoides L.) has been designated a "medicine food homology" fruit by the National Health Commission of China due to its nutritional value. In traditional Chinese ethnomedicine, Hippophae rhamnoides L. is commonly used to treat nonhealing wounds such as burns, sores, and gastric ulcers. The aim of this study was to explore the healing effects of the ethyl acetate extract of sea buckthorn seeds (SBS-EF) on burn wounds. Aim of the studyThe primary objectives of this research were to determine the most effective medicinal site of action for treating burns with sea buckthorn seeds (SBS) and to investigate the underlying material basis and mechanisms of their therapeutic effects. Materials and methodsThe effects of different components of SBS-EF on the proliferation and migration of human skin fibroblasts (HSFs) were evaluated via MTT assays, scratch assays, transwell assays, and hydroxyproline secretion analysis. SBS-EF displayed the greatest activity amongst the extracts. Subsequent analyses included network pharmacology methodology, molecular docking studies, ultraperformance liquid chromatography UPLC-Orbitrap-Exploris-120-MS and a severe second-degree burn rat model to investigate the chemical constituents and potential therapeutic mechanisms of the SBS-EF. ResultsIn vitro studies demonstrated the efficacy of SBS-EF in promoting HSF growth and migration. UPLC-Orbitrap-Exploris-120-MS analysis revealed that SBS-EF had ten major constituents, with flavonoids being the predominant compounds, especially catechin, quercetin, and kaempferol derivatives. Network pharmacology and molecular docking analyses indicated that SBS-EF may exert its healing effects by modulating the Wnt/β-catenin signalling pathway. Subsequent in vivo experiments demonstrated that SBS-EF accelerated burn wound healing in rats, increased hydroxyproline expression in skin tissue, facilitated skin structure repair, and enhanced collagen production and organisation over a 21 d period. Additionally, exposure to SBS-EF upregulated WNT3a and β-catenin while downregulating GSK-3β levels in rat skin tissue. ConclusionsThe wound healing properties of SBS-EF were attributed to its ability to enhance HSF growth and migration, increase hydroxyproline levels in the skin, promote collagen accumulation, reduce scarring, and decrease the skin water content. SBS-EF may also provide therapeutic benefits for burns by modulating the Wnt/β-catenin signalling pathway, as evidenced by its effective site and likely mechanism of action in the treatment of burned rats.

In Vitro Antibacterial and Anti-Inflammatory Properties of Imidazolium Poly(ionic liquids) Microspheres Loaded in GelMA-PEG Hydrogels.

Repairing damaged tissue caused by bacterial infection poses a significant challenge. Traditional antibacterial hydrogels typically incorporate various components such as metal antimicrobials, inorganic antimicrobials, organic antimicrobials, and more. However, drawbacks such as the emergence of multi-drug resistance to antibiotics, the low antibacterial efficacy of natural agents, and the potential cytotoxicity associated with metal antibacterial nanoparticles in hydrogels hindered their broader clinical application. In this study, we successfully developed imidazolium poly(ionic liquids) (PILs) polymer microspheres (APMs) through emulsion polymerization. These APMs exhibited notable antibacterial effectiveness and demonstrated minimal cell toxicity. Subsequently, we integrated the APMs into a gelatin methacryloyl (GelMA)-polyethylene glycol (PEG) hydrogel. This composite hydrogel not only showcased strong antibacterial and anti-inflammatory properties but also facilitated the migration of human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) and promoted osteogenic differentiation in vitro.

Sustained release of magnesium and zinc ions synergistically accelerates wound healing.

Skin wounds are a major medical challenge that threaten human health. Functional hydrogel dressings demonstrate great potential to promote wound healing. In this study, magnesium (Mg) and zinc (Zn) are introduced into methacrylate gelatin (GelMA) hydrogel via low-temperature magnetic stirring and photocuring, and their effects on skin wounds and the underlying mechanisms are investigated. Degradation testing confirmed that the GelMA/Mg/Zn hydrogel released magnesium ions (Mg2+) and zinc ions (Zn2+) in a sustained manner. The Mg2+ and Zn2+ not only enhanced the migration of human skin fibroblasts (HSFs) and human immortalized keratinocytes (HaCats), but also promoted the transformation of HSFs into myofibroblasts and accelerated the production and remodeling of extracellular matrix. Moreover, the GelMA/Mg/Zn hydrogel enhanced the healing of full-thickness skin defects in rats via accelerated collagen deposition, angiogenesis and skin wound re-epithelialization. We also identified the mechanisms through which GelMA/Mg/Zn hydrogel promoted wound healing: the Mg2+ promoted Zn2+ entry into HSFs and increased the concentration of Zn2+ in HSFs, which effectively induced HSFs to differentiate into myofibroblasts by activating the STAT3 signaling pathway. The synergistic effect of Mg2+ and Zn2+ promoted wound healing. In conclusion, our study provides a promising strategy for skin wounds regeneration.

Engineered BMSCs-Derived Exosomal miR-542-3p Promotes Cutaneous Wound Healing.

The healing of cutaneous wounds requires better strategies, which remain a challenge. Previous reports indicated that the therapeutic function of mesenchymal stem cells is mediated by exosomes. This work demonstrated the regenerative effects of engineered BMSCsderived Exosomal miR-542-3p in skin wound mouse models. Bone marrow mesenchymal stem cells (BMSCs) -derived exosomes (BMSCs-Exos) were isolated by ultracentrifugation and identified by Transmission Electron Microscope (TEM) and Nanoparticle Tracking Analysis (NTA). BMSCs-Exo was loaded with miRNA-542-3p by electroporation. We explored the effects of miRNA-542-3p-Exo on the proliferation and migration of Human Skin Fibroblasts (HSFs)/Human dermal microvascular endothelial cells (HMECs). In addition, The angiogenesis of HMECs was detected by Tube formation assay in vitro. The effects of miRNA-542-3p-Exo in the skin wound mouse model were detected by H&E staining, Masson staining, and immunofluorescence analysis. We assessed the effect of miRNA-542-3p-Exo on collagen deposition, new blood vessel formation, and wound remodeling in a skin wound mouse model. MiRNA-542-3p-Exos could be internalized by HSFs/HMECs and enhance the proliferation, migration, and angiogenesis of HSFs/HMECs in vitro and in vivo. The protein expression of collagen1/3 was significantly increased after miRNA-542-3p-Exo treatment in HSFs. In addition, the local injection of miRNA-542-3p-Exo promoted cellular proliferation, collagen deposition, neovascularization, and accelerated wound closure. This study suggested that miRNA-542-3p-Exo can stimulate HSFs/HMECs function. The treatment of miRNA-542-3p-Exo in the skin wound mouse model significantly promotes wound repair. The therapeutic potential of miRNA-542-3p-Exo may be a future therapeutic strategy for cutaneous wound healing.

S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion.

In plastic surgery, tissue expansion is widely used for repairing skin defects. However, low expansion efficiency and skin rupture caused by thin, expanded skin remain significant challenges in promoting skin regeneration during expansion. S100 calcium-binding protein A9 (S100A9) is essential in promoting wound healing; however, its effects on skin regeneration during tissue expansion remain unclear. The aim of the present study was to explore the role of S100A9 in skin regeneration, particularly collagen production to investigate its importance in skin regeneration during tissue expansion. The expression and distribution of S100A9 and its receptors-toll-like receptor 4 (TLR-4) and receptor for advanced glycation end products were studied in expanded skin. These characteristics were investigated in skin samples of rats and patients. Moreover, the expression of S100A9 was investigated in stretched keratinocytes in vitro. The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed. TAK-242 was used to inhibit the binding of S100A9 to TLR-4; the levels of collagen I (COL I), transforming growth factor beta (TGF-β), TLR-4 and phospho-extracellular signal-related kinase 1/2 (p-ERK1/2) in fibroblasts were determined. Furthermore, fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I, TGF-β, TLR-4 and p-ERK1/2 in fibroblasts were investigated. Additionally, the area of expanded skin, thickness of the dermis, and synthesis of COL I, TGF-β, TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin. Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix (ECM) in the expanded dermis. Furthermore, S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-β in fibroblasts via the TLR-4/ERK1/2 pathway. We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I, TGF-β, TLR-4 and p-ERK1/2 expression in skin fibroblasts. Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion. These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression. Our study laid the foundation for clinically improving tissue expansion using S100A9.

The use of babosa (Aloe vera) in treating burns: a literature review.

Alo vera is a centenary remedy use for minor wounds and burns, but its mechanism of wound healing has not been know since. This article will evaluate and gather evidence of the effectiveness and safety of the use of aloe vera in the treatment of burns. A systematic review was carried out on the databases: MEDLINE, LILACS, DECS, SCIELO, in the last 7 years, with the descriptors: "Aloe", "Burns" and "treatment". 16 articles were found. After using the exclusion criteria; research in non-humans and literature review; 5 articles were selected. The article Teplick et al. (2018) performed an in vitro clinical experiment in A. Vera solution, and demonstrated that there was proliferation and cell migration of human skin fibroblasts and keratinocytes, in addition to being protective in the death of keratonocytes. That is, it accelerates the healing of wounds. Muangman et al. (2016), evaluated 50 patients with 20% of the total body surface area burned with second-degree burns, between 18-60 years old, with half of the group receiving gauze dressings with soft paraffin containing 0.5% chlorhexidine acetate and the other half receiving polyester dressings containing extracts of medicinal plants mainly Aloe Vera. It had positive results, a higher healing speed and shorter hospital stay compared to the control group. Hwang et al. (2015) investigated the antioxidant effects of different extracts from 2,4,6,8,12 months of Aloe Vera. And the 6-month concentrated extract of 0.25 mg / mL had a higher content of flavonoids (9.750 mg catechin equivalent / g extract) and polyphenols (23.375 mg gallic acid equivalent / g extract) and the greater ferric reducing antioxidant power (0.047 mM equivalent ferrous sulfate / mg extract), that is, greater potential for free radical scavenging and also a protective effect against oxidative stress induced by tert-butyl hydroperoxide (t-BHP), suggesting evidence of a bioactive potential of A. vera . However, in the article Kolacz et al. (2014) suggested as an alternative treatment the use of Aloe Vera dressing in combination with honey, lanolin, olive oil, wheat germ oil, marshmallow root, wormwood, comfrey root, white oak bark, lobelia inflata, glycerin vegetable oil, beeswax and myrrh, without obtaining significant and conclusive results that would allow the conventional treatment of burns to be subsidized. Finally, in the article by Zurita and Gallegos (2017), it carried out a descriptive cross-sectional study with 321 people, both sexes between 17-76 years of age, of an inductive nature, exploring the experience of this population and their behavioral attitudes regarding the treatment of dermatoses. Aloe vera had 13.8% cited by individuals in the treatment of acne and 33.6% in the treatment of burns. Even with evidence that suggests the efficacy in the treatment of burns with the use of Aloe Vera extract, further clinical trials with larger sample space on the use of Aloe vera dressings in medium burns are suggested for further conclusions.

Human Vascular Endothelial Cells Promote the Secretion of Vascularization Factors and Migration of Human Skin Fibroblasts under Co-Culture and Its Preliminary Application.

The good treatment of skin defects has always been a challenge in the medical field, and the emergence of tissue engineering skin provides a new idea for the treatment of injured skin. However, due to the single seed cells, the tissue engineering skin has the problem of slow vascularization at the premonitory site after implantation into the human body. Cell co-culture technology can better simulate the survival and communication environment of cells in the human body. The study of multicellular co-culture hopes to bring a solution to the problem of tissue engineering. In this paper, human skin fibroblasts (HSFs) and human vascular endothelial cells (HVECs) were co-cultured in Transwell. The Cell Counting Kit 8 (CCK8), Transwell migration chamber, immunofluorescence, Western blot (WB), and real time quantitative PCR (RT-qPCR) were used to study the effects of HVECs on cell activity, migration factor (high mobility group protein 1, HMGB1) and vascularization factor (vascular endothelial growth factor A, VEGFA and fibroblast growth factor 2, FGF2) secretion of HSFs after co-cultured with HVECs in the Transwell. The biological behavior of HSFs co-cultured with HVECs was studied. The experimental results are as follows: (1) The results of cck8 showed that HVECS could promote the activity of HSFs. (2) HVECs could significantly promote the migration of HSFs and promote the secretion of HMGB1. (3) HVECs could promote the secretion of VEGFA and FGF2 of HSFs. (4) The HVECs and HSFs were inoculated on tissue engineering scaffolds at the ratio of 1:4 and were co-cultured and detected for 7 days. The results showed that from the third day, the number of HSFs was significantly higher than that of the control group without HVECs.

Autologous Bioactive Compound Concentrated Growth Factor Ameliorates Fistula Healing of Anal Fistula in a Pig Model and Promotes Proliferation and Migration of Human Skin Fibroblasts via Regulating the MEK/ERK Pathway.

Recent evidence suggested that autologous concentrated growth factor (CGF), a new bioactive compound from autologous blood is used widely as an ingenious biomaterial in tissue regeneration with anti-inflammatory properties. This study investigated whether CGF could be involved in the treatment of fistula healing in the anal fistula. For this purpose, the porcine anal fistula model was conducted using the rubber band ligation method and collected pig autogenic CGF to treat the fistulas. CGF treatment promoted fistula healing, which was reflected in the downregulation of inflammatory factors, upregulation of growth factors, and promoted epithelial-mesenchymal transition with increased collagen synthesis. Besides, 16S rRNA gene sequencing analysis of fistula tissues between the control and CGF groups showed that the microbial populations exhibiting significant differences were VadinCA02, Blastomonas, Deinococcus, Devosia, Sphingomonas, Rubrobacteria, and GW_34. CGF of volunteers were collected to process small interfering RNA- (siRNA-) ERK or siRNA-negative control transfected human skin fibroblasts (HSF). The results showed that CGF also promoted the proliferation and extracellular matrix-related functions in HSF, as well as activated the MEK/ERK pathway in vitro and in vivo. Finally, knockdown ERK reversed the effects of CGF in promoting wound healing in HSF. Collectively, our results suggest that the CGF as the bioactive compound from autologous blood exhibited great potential for repairing fistulas as well as promoting the proliferation and migration of human skin fibroblasts by triggering MEK/ERK signaling. These findings provided a fresh perspective for understanding the role of CGF in the management of fistulas.

Exosome Derived from Mesenchymal Stem Cells Alleviates Pathological Scars by Inhibiting the Proliferation, Migration and Protein Expression of Fibroblasts via Delivering miR-138-5p to Target SIRT1.

IntroductionThe therapies of using exosomes derived from mesenchymal stem cells (MSC-Exo) for wound healing and scar attenuation and micro RNAs (miRNAs) for regulation of genes by translational inhibition and mRNA destabilization obtained great achievements. Silent information regulator 1 (SIRT1) is the silent information, which has an intricate role in many biological processes. However, the effects of SIRT1 and miR-138-5p loaded in MSC-Exo on pathological scars remain unclear.MethodsMSC-Exo was isolated and identified by ultracentrifugation, transmission electron microscopy, nanoparticle size measuring instrument and Western blot assays. The relationship between SIRT1 and miR-138-5p was verified by a double-luciferase reporter assay. Cell Counting Kit-8, Τranswell, scratch, and Western blot assays were used to evaluate the proliferation and migration of human skin fibroblasts (HSFs), and the protein expression of SIRT1, NF-κB, α-SMA and TGF-β1 in HSFs, respectively. Flow cytometry was used to assess the apoptosis and cell cycle of HSFs affected by SIRT1.ResultsOur study demonstrated that miR-138-5p loaded in MSC-Exo could attenuate proliferation, migration and protein expression of HSFs-derived NF-κB, α-SMA, and TGF-β1 by targeting to SIRT1 gene, which confirmed the potential effects of MSC-Exo in alleviating pathological scars by performing as a miRNA’s delivery vehicle.ConclusionExosomes derived from MSCs acting as a delivery vehicle to deliver miR-138-5p can downregulate SIRT1 to inhibit the growth and protein expression of HSFs and attenuate pathological scars.

LncRNA MALAT1 from human adipose-derived stem cell exosomesaccelerates wound healing via miR-378a/FGF2 axis.

Aim: The effects of MALAT1from human adipose-derived stem cell(ADSC) exosomes in skin wound healingwere investigated. Material & methods: The viability, apoptosisand migration ability of human skin fibroblasts (HSFs) were evaluated by Cell Counting Kit-8 assay, flow cytometryand scratch assay, respectively. A mouse model was established to evaluate the role of exosomal MALAT1 in skin wound healing in vivo. Results: Human ADSC exosomes promoted the proliferation and migration of HSFs and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited HSF viability and migration, promoted HSF apoptosisand inhibited angiogenesis by upregulating miR-378a. Overexpression of miR-378a inhibited the migration and proliferation of HSFs by downregulating FGF2expression. ADSC exosomes promoted skin wound healing by mediating MALAT1 in vivo. Conclusion: Exosomal MALAT1 accelerated skin wound healing by regulating the miR-378a/FGF2 axis, suggesting that MALAT1 might be used as a potential target for cutaneous wound treatment.

MiR-24-3p obstructs the proliferation and migration of human skin fibroblasts after thermal injury by targeting PPAR-β and positively regulated by NF-κB.

Thermal injury repair is a complex process during which the maintenance of the proliferation and migration of human skin fibroblasts (HSFs) exert a crucial role. MicroRNAs have been proven to exert an essential function in repairing skin burns. This study delves into the regulatory effects of miR-24-3p on the migration and proliferation of HSFs that have sustained a thermal injury, thereby, providing deeper insight into thermal injury repair pathogenesis. The PPAR-β protein expression level progressively increased in a time-dependent manner on the 12th, 24th and 48th hour following the thermal injury of the HSFs. The knockdown of PPAR-β markedly suppressed the proliferation of and migration of HSF. Following thermal injury, the knockdown also promoted the inflammatory cytokine IL-6, TNF-α, PTGS-2 and P65 expression. PPAR-β contrastingly exhibited an opposite trend. A targeted relationship between PPAR-β and miR-24-3p was predicted and verified. miR-24-3p inhibited thermal injured HSF proliferation and migration and facilitated inflammatory cytokine expression through the regulation of PPAR-β. p65 directly targeted the transcriptional precursor of miR-24 and promoted miR-24 expression. A negative correlation between miR-24-3p expression level and PPAR-β expression level in rats' burnt dermal tissues was observed. Our findings reveal that miR-24-3p is conducive to rehabilitating the denatured dermis, which may be beneficial in providing effective therapy of skin burns.

Extracellular vesicles from human hepatic progenitor cells accelerate deep frostbite wound healing by promoting fibroblasts proliferation and inhibiting apoptosis

Frostbites are cold tissue damages frequently observed at high altitudes and under extremely cold conditions. Though their incidence rate is low, the resulting impact in affected patients can be very serious, often leading to amputations. Clinical management and the prediction of outcome can be of utmost importance to frostbite patients. A possible use of stem cell-derived extracellular vesicles (EVs) has been suggested for cutaneous wound healing and we, therefore, tested their use for the treatment of deep frostbite wound. To this end, the impacts of hHPC-derived EVs were evaluated in an in vivo animal model comprising of Kunming female mice as well as studied in vitro for the mechanism. We first characterized the EVs and these hHPC-derived EVs, when applied to treat frostbite wounds, accelerated wound healing in the in vivo animal model, as assessed by wound closure, re-epithelization thickness, collagen density and the expression of Collagen I and α-SMA. The proliferation and migration of human skin fibroblasts was also found to be increased by EVs in the in vitro experiments. The H2O2-induced apoptosis cell model, established to simulate the post-frostbite injury, was inhibited by EVs, with concomitant increase in the expression of Bcl-2 and decreased expression of Bax, further confirming the findings. Our novel results indicate that the application of EVs might be a promising strategy for deep frostbite wound healing.

Evaluating the effect of Luffa cylindrica stem sap on dermal fibroblasts; An invitro study

Luffa cylindrica stem sap (LuCS) has been traditionally used as a facial cosmetic supplement to enhance the skin condition of Asians. However, LuCS has yet to be described and there is no solid scientific evidence regarding the use of LuCS as an anti-wrinkle agent. In the present study, we have evaluated the functional effect of LuCS and its underlying mechanisms based on scientific evidence. Treatment with LuCS stimulated the growth and migration of human skin fibroblasts. LuCS treatment activated EGFR signaling via the enhanced expression of EGFR and down-regulation of PPARγ in human skin fibroblasts. Exposure to LuCS induced the synthesis of cellular type I procollagen and elastin in consort with the down-regulation of various proteinases including MMP-1, -2 and -9 in human skin fibroblasts. LuCS treatment also reversed the skin damage induced by UV-A irradiation in human skin fibroblasts. 3-bromo-3-methylisoxazol-5-amine was identified as the functional component using UPLC-MS-MS analysis and increased production of cellular type I procollagen. Collectively, these results suggest the efficacy of LuCS supplementation in improving the skin condition via anti-wrinkle effect.

5-hydroxymethylfurfural-embedded poly (vinyl alcohol)/sodium alginate hybrid hydrogels accelerate wound healing

Treating large acute or chronic wounds remains a challenging task because of a lack of effective methods to accelerate wound healing. Though growth factor-based wound products are found to be effective, they are costly and are potentially associated with increased cancer mortality. Effective, safe, and affordable strategies to tackle large or chronic wounds need to further be designed and developed. Here, we designed a new antioxidant-embedded hydrogel system for speeding up the wound healing process. We prepared multifunctional poly (vinyl alcohol)/sodium alginate (PVA/SA) hydrogels with the incorporation of 5-hydroxymethylfurfural (5-HMF) and silver nanoparticles (Ag-NPs), and investigated their physiochemical and biological properties in vitro and in vivo. PVA, SA, 5-HMF, and Ag-NPs were employed for good mechanical properties, good biocompatibility, anti-inflammation, and anti-bacterial activity, respectively. 5-HMF is commonly found in many food products (e.g. honey, coffee, and black garlic) and is known as an antioxidant. In our in vitro study, 5-HMF was found to effectively facilitate the proliferation and migration of human skin fibroblasts (HSF), and collagen production. Besides, 5-HMF-embedded PVA/SA hybrid hydrogels supported controlled release and good cell compatibility, and more importantly accelerated wound healing in vivo through ameliorated inflammation, enhanced angiogenesis/vascularization, increased collagen production, and promoted re-epithelialization.

Transition metal-doped cryogels as bioactive materials for wound healing applications.

Transition metals (TM) are essential microelements with various biological functions demanded in tissue regeneration applications. Little is known about therapeutic potential of TM within soft hydrogel biomaterials. The soluble divalent TM, such as Zn, Cu, Mn and Co, were stably incorporated into gelatin network during cryogelation. TM content in the resultant cryogels varied from 0.1 × 103 to 11.8 × 103 ppm, depending on the TM type and concentration in the reaction solution. Zn component was uniformly complexed with the gelatin scaffold according to elemental imaging, increasing the swelling of polymer walls and the G'/G″ values and also decreasing the size of cryogel macro-pores. Zn-doped cryogels supported migration of human skin fibroblasts (HSF); only upper Zn content of 11.8 × 103 ppm in the scaffold caused c.a. 50% inhibition of cell growth. Zn ions solubilized in culture medium were more active towards HSF (IC50 ≈ 0.3 mM). Treatment of splinted full-skin excisional wounds in rats with the Zn-doped and non-doped cryogels showed that Zn considerably promoted passing inflammatory/proliferation phases of healing process, inducing more intense dermis formation and structuration. The results show the feasibility of development of cryogel based formulations with different TM and support high phase-specific ability of the Zn-gelatin cryogels to repair acute wounds.

Infrared Skin‐Like Active Stretchable Electronics Based on Organic–Inorganic Composite Structures for Promotion of Cutaneous Wound Healing

AbstractRecent studies on flexible/stretchable medical electronics are almost all focusing on passive monitoring of physiological signs for medical diagnostics, but rare reports have been found on those for active therapeutic purposes. Here, a novel infrared skin‐like active stretchable electronics (ISASE) is introduced with the organic–inorganic composite design for promotion of cutaneous wound healing, which can be conformally mounted anywhere on the human body due to its excellent flexibility and stretchability. Comprehensive experiments, including the proliferation and migration of human skin fibroblasts and rat dermal fibroblasts in vitro, and various tests on wound healing of rats, show favorable effects of the ISASE on promoting the fibroblast migration and proliferation, reducing the inflammatory phase, stimulating the angiogenesis, and shorting the wound healing period. A typical ISASE significantly shortens the cure time for a wounded rat by at least two days compared with the normal treatment with 12 days cure. The mechanical tests confirm the validity of the ISASE when used in extreme large deformations (e.g., stretched by up to 80% strain), which enables the conformability with the human body. The present portable and wearable ISASE demonstrates great potential for cutaneous wound healing, which constitutes an important complement to the current applications in the healthcare field.

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

Background: The number of patients who has a daily intake of antihypertensive drugs is rising, due to an also rising prevalence of lifestyle diseases. Interestingly, knowledge about effects of these drugs in terms of wound healing is low. Objective: Based on a few differing studies, the idea arose that antihypertensives may have side effects on wound healing. Methods: Five antihypertensive drugs from different substance classes (metoprolol, amlodipine, ramipril, hydrochlorothiazide, candesartan) were investigated, in terms of possible impacts on cell metabolism and migration of human skin fibroblasts and keratinocytes. Additionally, histological and immunohistochemical analyses were performed in a 3-dimensional (3D) wound model addressing the influence on regeneration processes, such as cell migration, metabolic activity, apoptosis and epidermal thickness. Results: Hydrochlorothiazide and ramipril exerted inhibiting effects in nearly all analyses, interestingly, in serum equivalent doses. In contrast, candesartan and amlodipine induced slight positive effects in 2D as well as in 3D models. The previously described positive effects of β-blockers could only partially be confirmed by metoprolol. Antihypertensive drugs affected fibroblasts more than keratinocytes – whether positively or negatively. Conclusion: Antihypertensive drugs have an influence on keratinocytes and fibroblasts; they are not neutral. Candesartan has the most positive effects on skin cells. For angiotensin-converting enzyme inhibitors and thiazide diuretics, wound healing in a 3D model is delayed. β-Receptor blockers seem to improve wound healing to a small extent just like calcium channel blockers. These results should be evaluated in a clinical trial to verify their clinical relevance.

Side effects of frequently used oral antidiabetics on wound healing in vitro.

Lifestyle diseases such as diabetes and arteriosclerosis are rising in the increasingly aging society, and the number of patients with daily intake of glucose-lowering medication has also increased. Interestingly, knowledge about oral antidiabetics with regard to wound healing is scarce. Therefore, the aim of this study was to identify possible (side) effects of the most frequently prescribed oral antidiabetics on skin cells and wound healing. Four oral antidiabetics of different substance classes (i.e., metformin, glibenclamide, sitagliptin, repaglinide) were investigated with regard to the promotion of cell metabolism and migration of human skin fibroblasts and keratinocytes by XTT and scratch assays. In addition, histological and immunohistochemical analyses were performed in a 3D wound model to address the impact of the antidiabetics on regeneration processes, such as cell migration, fibroblast activity, epidermal thickness, and cell apoptosis. In comparison to systemic application, metformin displayed the most adverse effects in vitro in nearly all analyses, interestingly at serum equivalent concentrations. In contrast, sitagliptin and glibenclamide had a slight but insignificant effect on fibroblasts compared with keratinocytes. Repaglinide tended to have a negative influence on keratinocyte metabolism. Interestingly, antidiabetics generally induced a significantly enhanced rate of apoptosis in fibroblasts, with the exception of repaglinide.Antidiabetics influenced key players in wound healing, namely, keratinocytes and fibroblasts. Particularly, metformin impaired human skin cells. These findings should be kept in mind in further studies because of their putative relevance in patients suffering from chronic wounds that do not respond to various wound therapies.