Bioinspired Intrinsic Versatile Hydrogel Fabricated by Amyloidal Toxin Simulant-Based Nanofibrous Assemblies for Accelerated Diabetic Wound Healing

Qize Xuan; Feng Jiang; Hao Dong; Wenxue Zhang; Feiyang Zhang; Tonghao Ma; Jiafeng Zhuang; Jinlong Yu; Yibing Wang; Hao Shen; Chao Chen; Ping Wang

doi:10.1002/adfm.202106705

Bioinspired Intrinsic Versatile Hydrogel Fabricated by Amyloidal Toxin Simulant-Based Nanofibrous Assemblies for Accelerated Diabetic Wound Healing

Qize Xuan, Feng Jiang, Hao Dong, Wenxue Zhang, Feiyang Zhang, Tonghao Ma, Jiafeng Zhuang, Jinlong Yu, Yibing Wang, Hao Shen, Chao Chen, Ping Wang

Bioproducts and Biosystems Engineering

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH₂, FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus). The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b-sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillin-resistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drug-related side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the management of microbe-infected diabetic wounds.

Original language	English (US)
Article number	2106705
Journal	Advanced Functional Materials
Volume	31
Issue number	49
DOIs	https://doi.org/10.1002/adfm.202106705
State	Published - Dec 2 2021

Bibliographical note

Funding Information:
Q.X. and F.J. contributed equally to this work. This work was sponsored by the National Natural Science Foundation of China (Grant Nos. 81772364, 21908059, 41907318, and 21636003), Medical Guidance Scientific Research Support Project of Shanghai Science and Technology Commission (Grant No. 19411962600), the China Postdoctoral Science Foundation (Grant No. 2019M651419), Shanghai Sailing Program (Grant No. 19YF1410900), the Fundamental Research Funds for the Central Universities (Grant No. 22221818014), the Shanghai Post‐doctoral Excellence Program (Grant No. 2018011), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. The authors also thank the Research Centre of Analysis and Test of East China University of Science and Technology for the help with the TEM characterization of hydrogel.

Funding Information:
Q.X. and F.J. contributed equally to this work. This work was sponsored by the National Natural Science Foundation of China (Grant Nos. 81772364, 21908059, 41907318, and 21636003), Medical Guidance Scientific Research Support Project of Shanghai Science and Technology Commission (Grant No. 19411962600), the China Postdoctoral Science Foundation (Grant No. 2019M651419), Shanghai Sailing Program (Grant No. 19YF1410900), the Fundamental Research Funds for the Central Universities (Grant No. 22221818014), the Shanghai Post-doctoral Excellence Program (Grant No. 2018011), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. The authors also thank the Research Centre of Analysis and Test of East China University of Science and Technology for the help with the TEM characterization of hydrogel.

Publisher Copyright:
© 2021 Wiley-VCH GmbH

Keywords

amyloid
chronic wounds
intrinsic versatile hydrogel
peptide assembly
wound dressings

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/adfm.202106705

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title = "Bioinspired Intrinsic Versatile Hydrogel Fabricated by Amyloidal Toxin Simulant-Based Nanofibrous Assemblies for Accelerated Diabetic Wound Healing",

abstract = "Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH2, FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus). The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b-sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillin-resistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drug-related side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the management of microbe-infected diabetic wounds.",

keywords = "amyloid, chronic wounds, intrinsic versatile hydrogel, peptide assembly, wound dressings",

author = "Qize Xuan and Feng Jiang and Hao Dong and Wenxue Zhang and Feiyang Zhang and Tonghao Ma and Jiafeng Zhuang and Jinlong Yu and Yibing Wang and Hao Shen and Chao Chen and Ping Wang",

note = "Funding Information: Q.X. and F.J. contributed equally to this work. This work was sponsored by the National Natural Science Foundation of China (Grant Nos. 81772364, 21908059, 41907318, and 21636003), Medical Guidance Scientific Research Support Project of Shanghai Science and Technology Commission (Grant No. 19411962600), the China Postdoctoral Science Foundation (Grant No. 2019M651419), Shanghai Sailing Program (Grant No. 19YF1410900), the Fundamental Research Funds for the Central Universities (Grant No. 22221818014), the Shanghai Post‐doctoral Excellence Program (Grant No. 2018011), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. The authors also thank the Research Centre of Analysis and Test of East China University of Science and Technology for the help with the TEM characterization of hydrogel. Funding Information: Q.X. and F.J. contributed equally to this work. This work was sponsored by the National Natural Science Foundation of China (Grant Nos. 81772364, 21908059, 41907318, and 21636003), Medical Guidance Scientific Research Support Project of Shanghai Science and Technology Commission (Grant No. 19411962600), the China Postdoctoral Science Foundation (Grant No. 2019M651419), Shanghai Sailing Program (Grant No. 19YF1410900), the Fundamental Research Funds for the Central Universities (Grant No. 22221818014), the Shanghai Post-doctoral Excellence Program (Grant No. 2018011), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. The authors also thank the Research Centre of Analysis and Test of East China University of Science and Technology for the help with the TEM characterization of hydrogel. Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",

year = "2021",

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doi = "10.1002/adfm.202106705",

language = "English (US)",

volume = "31",

journal = "Advanced Functional Materials",

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T1 - Bioinspired Intrinsic Versatile Hydrogel Fabricated by Amyloidal Toxin Simulant-Based Nanofibrous Assemblies for Accelerated Diabetic Wound Healing

AU - Xuan, Qize

AU - Jiang, Feng

AU - Dong, Hao

AU - Zhang, Wenxue

AU - Zhang, Feiyang

AU - Ma, Tonghao

AU - Zhuang, Jiafeng

AU - Yu, Jinlong

AU - Wang, Yibing

AU - Shen, Hao

AU - Chen, Chao

AU - Wang, Ping

N1 - Funding Information: Q.X. and F.J. contributed equally to this work. This work was sponsored by the National Natural Science Foundation of China (Grant Nos. 81772364, 21908059, 41907318, and 21636003), Medical Guidance Scientific Research Support Project of Shanghai Science and Technology Commission (Grant No. 19411962600), the China Postdoctoral Science Foundation (Grant No. 2019M651419), Shanghai Sailing Program (Grant No. 19YF1410900), the Fundamental Research Funds for the Central Universities (Grant No. 22221818014), the Shanghai Post‐doctoral Excellence Program (Grant No. 2018011), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. The authors also thank the Research Centre of Analysis and Test of East China University of Science and Technology for the help with the TEM characterization of hydrogel. Funding Information: Q.X. and F.J. contributed equally to this work. This work was sponsored by the National Natural Science Foundation of China (Grant Nos. 81772364, 21908059, 41907318, and 21636003), Medical Guidance Scientific Research Support Project of Shanghai Science and Technology Commission (Grant No. 19411962600), the China Postdoctoral Science Foundation (Grant No. 2019M651419), Shanghai Sailing Program (Grant No. 19YF1410900), the Fundamental Research Funds for the Central Universities (Grant No. 22221818014), the Shanghai Post-doctoral Excellence Program (Grant No. 2018011), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. The authors also thank the Research Centre of Analysis and Test of East China University of Science and Technology for the help with the TEM characterization of hydrogel. Publisher Copyright: © 2021 Wiley-VCH GmbH

PY - 2021/12/2

Y1 - 2021/12/2

N2 - Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH2, FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus). The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b-sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillin-resistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drug-related side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the management of microbe-infected diabetic wounds.

AB - Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH2, FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus). The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b-sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillin-resistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drug-related side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the management of microbe-infected diabetic wounds.

KW - amyloid

KW - chronic wounds

KW - intrinsic versatile hydrogel

KW - peptide assembly

KW - wound dressings

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DO - 10.1002/adfm.202106705

M3 - Article

AN - SCOPUS:85114469678

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JO - Advanced Functional Materials

JF - Advanced Functional Materials

SN - 1616-301X

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ER -

Bioinspired Intrinsic Versatile Hydrogel Fabricated by Amyloidal Toxin Simulant-Based Nanofibrous Assemblies for Accelerated Diabetic Wound Healing

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

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