Rat epidermal stem cells promote the angiogenesis of full-thickness wounds

Huang, Shaobin; Hu, Zhicheng; Wang, Peng; Zhang, Yi; Cao, Xiaoling; Dong, Yunxian; Cheng, Pu; Xu, Hailin; Zhu, Wenkai; Tang, Bin; Zhu, Jiayuan

doi:10.1186/s13287-020-01844-y

Cited by 17 publications

(10 citation statements)

References 24 publications

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“…A large number of researches have demonstrated that the growth of new blood vessels could form the granulation tissue and improve wound microcirculation. [53][54][55] In order to evaluate the efficacy of the hydrogel dressing in preventing infection, tumor necrosis factor-alpha (TNF-) and interleukin 6 (IL-6), which are known to play a key role in stimulating the inflammatory response, were selected as the indicators to assess the inflammation of wounds on the 7th day. The immunofluorescence staining and quantitative analysis results of TNF-and IL-6 are shown in Figure 7a,b, which reveal the higher expression of TNF-(P<0.05) and IL-6 (P<0.01) in the control group than that in the PNA-G/NIR group.…”

Section: Immunohistochemical Analysesmentioning

confidence: 99%

Smart Asymmetric Hydrogel with Integrated Multi‐Functions of NIR‐Triggered Tunable Adhesion, Self‐Deformation, and Bacterial Eradication

Feng

Shi

Chen

et al. 2021

Adv Healthcare Materials

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Multifunctional hydrogels acting as wound dressing have received extensive attention in soft tissue repair; however, it is still a challenge to develop a non-antibiotic-dependent antibacterial hydrogel that has tunable adhesion and deformation to achieve on-demand removal. Herein, an asymmetric adhesive hydrogel with near-infrared (NIR)-triggered tunable adhesion, self-deformation, and bacterial eradication is designed. The hydrogel is prepared by the crosslinking polymerization of N-isopropylacrylamide and acrylic acid, during the sedimentation of conductive PPy-PDA nanoparticles based on the polymerization of pyrrole (Py) and dopamine (DA). Due to the conversion capacity from NIR light into heat for PPy-PDA NPs, the formed temperature-sensitive hydrogel exhibits tissue adhesive as well as NIR-triggered tunable adhesion and self-deformation property, which can achieve an on-demand dressing refreshing. Systematically in vitro/in vivo antibacterial experiments indicate that the hydrogel shows excellent disinfection capability to both Gram-negative and Gram-positive bacteria. The in vivo experiments in a full-layer cutaneous wound model demonstrate that the hydrogel has a good treatment effect to promote wound healing. Overall, the asymmetric hydrogel with tunable adhesion, self-deformation, conductive, and photothermal antibacterial activity may be a promising candidate to fulfill the functions of adhesion on skin tissue, easy removing on-demand, and accelerating the wound healing process.

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Section: Immunohistochemical Analysesmentioning

confidence: 99%

Smart Asymmetric Hydrogel with Integrated Multi‐Functions of NIR‐Triggered Tunable Adhesion, Self‐Deformation, and Bacterial Eradication

Feng

Shi

Chen

et al. 2021

Adv Healthcare Materials

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“…To assess the condition of wound healing in mouse backs, the wound was photographed by a digital camera (Nikon, Tyoto) on days 0, 3, 7, and 14 ( Huang et al, 2020 ). The wound closure rate was quantified by ImageJ software (Bethesda, MD) and calculated as follows: t-t 0 /t 0 × 100% (t: the wound healing was assessed, t 0 : initial wounding).…”

Section: Experimental Evaluationmentioning

confidence: 99%

Uncovering the pharmacological mechanisms of Zizhu ointment against diabetic ulcer by integrating network analysis and experimental evaluation in vivo and in vitro

Wang

Huang

et al. 2022

Front. Pharmacol.

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Diabetic ulcer (DU) has been recognized as one of the most prevalent and serious complications of diabetes. However, the clinical efficacy of standard treatments for DU remains poor. Traditional Chinese medicine (TCM) shows a positive therapeutic effect on DU. Specifically, Zizhu ointment (ZZO) has been widely used to treat DU in long-term clinical practice, but the exact mechanism by which it promotes DU wound healing remains unknown. In this study, network analysis and high-performance liquid chromatography–high resolution mass spectrometry (UPLC-HRMS) were conducted to identify the active compounds of ZZO. We detected isovalerylshikonin (ISO), mandenol, daidzein, kaempferol, and formononetin in both network analysis and UPLC-HRMS. Moreover, ZZO could ameliorate DU by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and inflammation signaling pathways, according to the results of KEGG analysis. We established a DU mouse model with a high-fat diet and streptozotocin injection in vivo to evaluate the network analysis result. The experimental results showed that ZZO could inhibit inflammation, remodel fibrous tissue, and promote angiogenesis in the DU area, facilitating wound healing in DU mice. Moreover, the PI3K/AKT signaling pathway was indeed activated by ZZO treatment, promoting macrophage M2 polarization. In addition, we used molecular docking technology to evaluate the binding sites between ZZO and the PI3K/AKT pathway. The results showed that ISO has a good binding interaction with AKT. Moreover, ISO promoted M2 polarization in macrophages in a dose-dependent manner in vitro. Our study found that ZZO could promote DU wound healing by inhibiting inflammation, which was achieved by macrophage M2 polarization through activating the PI3K/AKT pathway. Further studies have demonstrated that ISO plays major role in the above process. These findings provide a theoretical basis for further preclinical evaluation and lay a foundation for nano-gel compound treatment with ZZO.

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“…Our previous study showed that EpSCs could proliferate and differentiate in the wound bed and observed that EpSCs form new blood vessels in the wound bed [ 23 ]. We hypothesized that the vascularization process inside the dermal substitutes implanted into the wound was similar to that in the site of damage.…”

Section: Introductionmentioning

confidence: 99%

Single-stage transplantation combined with epidermal stem cells promotes the survival of tissue-engineered skin by inducing early angiogenesis

Wang

Yang

et al. 2023

Stem Cell Res Ther

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Background The composite transplantation of a split-thickness skin graft (STSG) combined with an acellular dermal matrix (ADM) is a promising repair method for full-thickness skin defects. Due to delayed vascularization of the ADM, no currently available engineered skin tissue is able to permanently cover full-thickness skin defects via a single-stage procedure. Epidermal stem cells (EpSCs) have been found to promote angiogenesis in the wound bed. Whether EpSCs can induce early angiogenesis of dermal substitutes and promote the survival of single-stage tissue-engineered skin transplantation needs to be further studied. Methods In vitro, rat vascular endothelial cells (RVECs) were treated with the supernatant of EpSCs cultured in ADM and stimulated for 48 h. RVECs were analysed by RNA sequencing and tube formation assays. For the in vivo experiment, 75 rats were randomly divided into five groups: ADM, ADM + EpSCs (AE), STSG, ADM + STSG (AS), and ADM + STSG + EpSCs (ASE) groups. The quality of wound healing was estimated by general observation and H&E and Masson staining. The blood perfusion volume was evaluated using the LDPI system, and the expression of vascular markers was determined by immunohistochemistry (IHC). Results The active substances secreted by EpSCs cultured in ADM promoted angiogenesis, as shown by tube formation experiments and RNA-seq. EpSCs promoted epithelialization of the ADM and vascularization of the ADM implant. The ASE group showed significantly increased skin graft survival, reduced skin contraction, and an improved cosmetic appearance compared with the AS group and the STSG control group. Conclusions In summary, our findings suggest that EpSCs promote the formation of new blood vessels in dermal substitutes and support one-step transplantation of tissue-engineered skin, and thereby provide new ideas for clinical application.

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Rat epidermal stem cells promote the angiogenesis of full-thickness wounds

Cited by 17 publications

References 24 publications

Smart Asymmetric Hydrogel with Integrated Multi‐Functions of NIR‐Triggered Tunable Adhesion, Self‐Deformation, and Bacterial Eradication

Smart Asymmetric Hydrogel with Integrated Multi‐Functions of NIR‐Triggered Tunable Adhesion, Self‐Deformation, and Bacterial Eradication

Uncovering the pharmacological mechanisms of Zizhu ointment against diabetic ulcer by integrating network analysis and experimental evaluation in vivo and in vitro

Single-stage transplantation combined with epidermal stem cells promotes the survival of tissue-engineered skin by inducing early angiogenesis

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