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Dihydromyricetin-Incorporated Multilayer Nanofibers Accelerate Chronic Wound Healing by Remodeling the Harsh Wound Microenvironment

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Abstract

The harsh microenvironment in wound (HMW) remains a major obstacle to chronic wound healing. Although a series of bioactive materials have been developed, few of them are multi-functional and able to accelerate wound healing via precisely remodeling the HMW. Herein, a series of dihydromyricetin (DHM)-incorporated multilayer nanofibers (termed DQHP-n, n = 0, 2, 6 and 10) are fabricated using a layer-by-layer (LBL) self-assembly technique. The average diameters of DQHP-n significantly increase from 0.30 ± 0.16 μm to 0.84 ± 0.28 μm (P < 0.05) along with the n value increased from 0 to 10, the tensile strength of that is also significantly improved from 1.12 ± 0.15 MPa to 2.16 ± 0.30 MPa (P < 0.05), and the water contact angle of that significantly decreases from 129.1 ± 1.5° to 76.6 ± 3.9° (P < 0.05). The DQHP-n are found to be biocompatible, in which DQHP-6 promoted cell migration through activation of the epithelial–mesenchymal transformation (EMT) pathway and reconstruction of the HMW by stopping bleeding, killing bacteria, eliminating inflammation, and scavenging reactive oxygen species (ROS). The in vivo evaluation is carried out via an E. coli-infected rat skin regeneration model. The DQHP-6 group demonstrates the best effect, as it healed up to 98.5 ± 1.0% of the wound area at day 15. DQHP-6 differentially regulates the mRNA expressions of several cytokines (FGF2, PDGF, IL-1α, IL-6, IL10, and TGF-β), which ends to reductions of total inflammatory cells (CD45+ cells) and M1 macrophages (CD80+ and CD86+ cells), proliferation of host cell (Ki67+ cells), and enhancement of collagen synthesis. In conclusion, DQHP-6 exhibits multifunctional properties for HMW, and can serve as a promising wound dressing for clinical transformation.

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Abbreviations

HMW:

Harsh Microenvironment in Wound

DHM:

Dihydromyricetin

QC:

Quaternized chitosan

HA:

hyaluronic acid

LBL:

Layer-by-layer

EMT:

Epithelial–mesenchymal transformation

ROS:

Reactive oxygen species

CSI:

Chronic skin injuries

TEWDs:

Tissue engineering wound dressings

ECM:

Extracellular matrix

PCL:

Polycaprolactone

FGF2:

fibroblast growth factor-2

PDGF:

Platelet-derived growth factor

TCBs:

Traditional Chinese herbs

FDA:

the Food and Drug administration

NMPA:

National Medical Products Administration

FT-IR:

Fourier transform infrared spectrum

XRD:

X-ray diffraction spectrum

NS:

Normal saline

E. coli :

Escherichia coli

S. aureus :

Staphylococcus aureus

MRSA:

Methicillin-resistant Staphylococcus aureus

NO:

Nitric oxide

HR:

Hemolysis ratio.

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Acknowledgements

The authors thank Prof. Weikang Hu from Huazhong University of Science and Technology for the great support. This work was financially supported by the Fellowship of China National Postdoctoral Program for Innovative Talants (BX20220240), the Improvement Project for Theranostic Ability on Difficulty Miscellaneous Disease (Tumor) from National Health Commission of China (ZLYNXM202006), the Chinese Central Special Fund for Local Science and Technology Development of Hubei Province (2018ZYYD023), and the Science and Technology Department of Hubei Province Key Project (2018ACA159).

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  1. Zijian Wang and Wenjie You contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Zhongnan Hospital of Wuhan University, 430071, Wuhan, China

    Zijian Wang, Wenjie You, Wang Wang, Yu Xiao & Xinghuan Wang

  2. Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Disease, School of Basic Medicine Sciences, TaiKang Medical School, Wuhan University, 430071, Wuhan, China

    Zijian Wang, Weiqun Tian & Yun Chen

  3. Center for Quantitative Biology, School of Life Sciences, Peking University, 100871, Beijing, China

    Fangjin Chen

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  1. Zijian Wang
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Wang, Z., You, W., Wang, W. et al. Dihydromyricetin-Incorporated Multilayer Nanofibers Accelerate Chronic Wound Healing by Remodeling the Harsh Wound Microenvironment. Adv. Fiber Mater. 4, 1556–1571 (2022). https://doi.org/10.1007/s42765-022-00180-5

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