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Nano Research 2024, 17(3): 1737-1747 https://doi.org/10.1007/s12274-023-5958-6
Research Article | Issue | Published: 15 July 2023

Visible light cross-linking and bioactive peptides loaded integrated hydrogel with sequential release to accelerate wound healing complicated by bacterial infection

Show Author's Information Guiyan Wang1,§,  Ning Yuan2,§,  Jun Zhang2,  Man Qin1,  Suwei Dong2( ),  Yuguang Wang3( )
Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, China
State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China

§ Guiyan Wang and Ning Yuan contributed equally to this work.

Keywords:
antimicrobial peptide, sequential release, visible-light crosslinking hydrogel, wound therapy, vascular endothelial growth factor (VEGF) mimetic peptide
Topics:
Biotechnology
Cite this article:
Wang G, Yuan N, Zhang J, et al. Visible light cross-linking and bioactive peptides loaded integrated hydrogel with sequential release to accelerate wound healing complicated by bacterial infection. Nano Research, 2024, 17(3): 1737-1747. https://doi.org/10.1007/s12274-023-5958-6
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Abstract Full text Electronic supplementary material About this article

The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge. The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected wounds. Here, a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is developed. The antibacterial peptide that consists of 11 residues (CM11, WKLFKKILKVL) is loaded onto acrylate-modified gelatin through charge interactions. A vascular endothelial growth factor mimetic peptide KLT (KLTWQELYQLKYKGI) with a GCG (Gly-Cys-Gly) modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene reaction. In this reaction, the acrylate gelatin undergoes cross-linkage within seconds. Based on the physical/chemical double crosslinking strategy, the bioactive peptides achieve sustained and sequential release. The results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus (MRSA) growth through the rapid release of CM11 peptides at early stage; it forms obvious growth inhibition zones against pathogenic bacterial strains. Moreover, cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT peptides. In a mouse skin wound infected with self-luminous MRSA, the CM11/KLT-functionalized hydrogels enhance wound healing, with rapidly bacterial infection reduction, lower expression of inflammatory factors, and neovascularization promotion. These results suggest that the rationally designed, sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.


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Electronic supplementary material
About this article

Visible light cross-linking and bioactive peptides loaded integrated hydrogel with sequential release to accelerate wound healing complicated by bacterial infection

Show Author's information Guiyan Wang1,§, Ning Yuan2,§, Jun Zhang2, Man Qin1, Suwei Dong2( ), Yuguang Wang3( )
Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, China
State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, and School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China

§ Guiyan Wang and Ning Yuan contributed equally to this work.

Abstract

The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge. The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected wounds. Here, a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is developed. The antibacterial peptide that consists of 11 residues (CM11, WKLFKKILKVL) is loaded onto acrylate-modified gelatin through charge interactions. A vascular endothelial growth factor mimetic peptide KLT (KLTWQELYQLKYKGI) with a GCG (Gly-Cys-Gly) modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene reaction. In this reaction, the acrylate gelatin undergoes cross-linkage within seconds. Based on the physical/chemical double crosslinking strategy, the bioactive peptides achieve sustained and sequential release. The results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus (MRSA) growth through the rapid release of CM11 peptides at early stage; it forms obvious growth inhibition zones against pathogenic bacterial strains. Moreover, cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT peptides. In a mouse skin wound infected with self-luminous MRSA, the CM11/KLT-functionalized hydrogels enhance wound healing, with rapidly bacterial infection reduction, lower expression of inflammatory factors, and neovascularization promotion. These results suggest that the rationally designed, sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.

Keywords: antimicrobial peptide, sequential release, visible-light crosslinking hydrogel, wound therapy, vascular endothelial growth factor (VEGF) mimetic peptide

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Publication history
Copyright
Acknowledgements

Publication history

Received: 18 May 2023
Revised: 14 June 2023
Accepted: 23 June 2023
Published: 15 July 2023
Issue date: March 2024

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

The authors are grateful for the financial support from the Research Foundation of Peking University School and Hospital of Stomatology (No. PKUSS20210113), the National Natural Science Foundation of China (Nos. 51972003，and 52271127), the National Key Technologies R&D Program (No. 2022YFC2403203-3), Intergovernmental International Cooperation Project of Beijing Municipal Science and Technology Commission (No. Z221100002722004).

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