Biodegradable hydrogels with photodynamic antibacterial activity promote wound healing and mitigate scar formation

Zhang, Chen; Yang, Dan; Wang, Taibao; Nie, Xuan; Chen, Guang; Wang, Long‐Hai; You, Ye‐Zi; Wang, Qin

doi:10.1039/d2bm01493a

Cited by 21 publications

(11 citation statements)

References 45 publications

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“…Since that bacterial proliferation at the wound site is one of the major reasons for delayed healing and abnormal scarring ( Frykberg and Banks, 2015 ; Zhang et al, 2022 ), and Gallium and Quercetin are documented of anti-bacterial property ( Hu et al, 2022 ; Qin J. et al, 2022 ), we went on to investigate whether QCT@GNP-Ga exerted great anti-bacterial effect. The surface of the agarose medium was coated with QCT@GNP-Ga and then inoculated with S. aureus and E. coli to observe its anti-bacterial activity.…”

Section: Resultsmentioning

confidence: 99%

Gallium-modified gelatin nanoparticles loaded with quercetin promote skin wound healing via the regulation of bacterial proliferation and macrophage polarization

Yang

Shi

Zhou

et al. 2023

Front. Bioeng. Biotechnol.

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Background: Wound healing is a complicated process involving multiple cell components and can help the re-establishment of the skin’s barrier function. Previous studies have pointed out that bacterial infection and sustained inflammatory reactions are the main causes of the delay of wound closure and scar formation during wound healing. The effect of current approaches for scar-free wound repair still faces many challenges, and alternative therapeutic methods are urgently needed to be established.Methods: The basic characteristics of the new-designed nanoparticles were clarified through the characterization of the material. The biocompatibility of the nanoparticles, as well as its effect on fibroblast function, anti-bacterial capacity, inflammation suppressive role, and the underlying mechanism were further verified by a panel of biochemical assays in vitro. Ultimately, pre-clinical rat model was employed to testify its role in wound healing and scar formation in vivo.Results: Firstly, gallium-modified gelatin nanoparticles loaded with quercetin was successfully established, displaying good biocompatibility and facilitative effect on fibroblast function. In addition, the nanoparticles showed prominent anti-bacterial and inflammation-suppressive effects. What’s more important, the nanoparticles could also induce the polarization of macrophages from M1 to M2 phenotype to exert its inflammatory inhibitory role through TGF-β/Smad signaling pathway. Ultimately, in vivo experiment showed that the nanoparticles could effectively promote wound repair and inhibit scar formation during the process of wound healing.Conclusion: Taken together, the new nanoparticles have good anti-bacterial and anti-scar formation effects and great potential in the field of skin wound repair, which provides a promising therapeutic strategy for wound treatment.

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Section: Resultsmentioning

confidence: 99%

Gallium-modified gelatin nanoparticles loaded with quercetin promote skin wound healing via the regulation of bacterial proliferation and macrophage polarization

Yang

Shi

Zhou

et al. 2023

Front. Bioeng. Biotechnol.

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“…These materials are becoming important as a promising solution for wound management due to their tunability, softness, permeability, biocompatibility, or biodegradability. − In the context of drug delivery, hydrogels benefit from their porosity, which enables drug encapsulation within a 3D polymeric network. Some antibacterial hydrogels have been particularly valuable in the context of light-induced therapies such as antimicrobial photodynamic therapy (aPDT). − aPDT combines light, molecular oxygen, and a photosensitizer to generate reactive oxygen species (ROS) that oxidize lipids, proteins, DNA, and other biomolecules, leading to bacterial inactivation. − Good transparency is, therefore, needed for hydrogels to perform well in aPDT, especially for wound dressing applications, and previous work has focused on optimizing their optical properties. , It was shown that electron-beam polymerized polyethylene glycol diacrylate (PEGDA) hydrogels have a higher transmittance over a broader wavelength range compared to their UV-cured counterparts, reaching values well above 90% …”

Section: Introductionmentioning

confidence: 99%

In Situ Single-Cell Bacterial Imaging Provides Mechanistic Insight into the Photodynamic Action of Photosensitizer-Loaded Hydrogels

Ortega,

Şener Raman,

Schulze

et al. 2024

ACS Appl. Mater. Interfaces

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Hydrogels, three-dimensional hydrophilic polymeric networks with high water retaining capacity, have gained prominence in wound management and drug delivery due to their tunability, softness, permeability, and biocompatibility. Electron-beam polymerized poly-(ethylene glycol) diacrylate (PEGDA) hydrogels are particularly useful for phototherapies such as antimicrobial photodynamic therapy (aPDT) due to their excellent optical properties. This work takes advantage of the transparency of PEGDA hydrogels to investigate bacterial responses to aPDT at the single-cell level, in real-time and in situ. The photosensitizer methylene blue (MB) was loaded in PEGDA hydrogels by using two methods: reversible loading and irreversible immobilization within the 3D polymer network. MB release kinetics and singlet oxygen generation were studied, revealing the distinct behaviors of both hydrogels. Real-time imaging of Escherichia coli was conducted during aPDT in both hydrogel types, using the Min protein system to report changes in bacterial physiology. Min oscillation patterns provided mechanistic insights into bacterial photoinactivation, revealing a dependence on the hydrogel preparation method. This difference was attributed to the mobility of MB within the hydrogel, affecting its direct interaction with bacterial membranes. These findings shed light on the complex interplay between hydrogel properties and the bacterial response during aPDT, offering valuable insights for the development of antibacterial wound dressing materials. The study demonstrates the capability of real-time, single-cell fluorescence microscopy to unravel dynamic bacterial behaviors in the intricate environment of hydrogel surfaces during aPDT.

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“…[23,24] It has been demonstrated that verteporfin-mediated PDT is efficient in producing ROS and killing bacteria. [25,26] Furthermore, verteporfin is regarded as an inhibitor of the Hippo-Yes-associated protein-1 (YAP) signaling pathway, which plays an important role in regulating the proliferation, apoptosis, and an-giogenesis of endothelial cells (ECs). [27,28] It has been reported that verteporfin is able to inhibit the angiogenesis of ECs without light activation.…”

Section: Introductionmentioning

confidence: 99%

Three‐Step Regenerative Strategy: Multifunctional Bilayer Hydrogel for Combined Photothermal/Photodynamic Therapy to Promote Drug‐Resistant Bacteria‐Infected Wound Healing

Zha,

Zhang,

et al. 2023

Adv Funct Materials

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The drug‐resistant bacterial‐infected skin wound is still a severe healthcare problem. Uncontrolled bacterial infection, abundant reactive oxygen species (ROS) content, and prolonged inflammatory response are detrimental to wound healing. Moreover, excessive vessel growth can result in unsatisfactory scar formation. Herein, a three‐step regenerative strategy based on a bilayered gelatin/acryloyl β‐cyclodextrin (BGACD) hydrogel containing physical host–guest complexations and chemical crosslinks is proposed. The hydrogel is loaded with humic acids (HAs) and astragaloside IV (AS) in the lower layer and verteporfin (Vt) in the upper layer. Different gelatin/acryloyl β‐cyclodextrin ratios endow the lower and upper layers of the hydrogel with different degradation rates. Under light irradiation, the combination of HAs‐induced photothermal therapy (PTT) and verteporfin‐induced photodynamic therapy effectively inhibits MRSA growth. The HAs and astragaloside IV are released from the lower layer to scavenge ROS and promote M2 macrophage polarization and angiogenesis during the inflammation and early proliferation phases, while verteporfin releases from the upper layer suppress excessive vessel growth during the late proliferation and remodeling phases. The HAs‐AS@Vt@BGACD hydrogel successfully achieves rapid and scarless wound healing in an MRSA‐infected wound model in rats. Therefore, the HAs‐AS@Vt@BGACD hydrogel shows promising potential for the treatment of drug‐resistant bacteria‐infected skin wound healing.

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Biodegradable hydrogels with photodynamic antibacterial activity promote wound healing and mitigate scar formation

Abstract: Bacterial proliferation and disordered extracellular matrix (ECM) at the wound site are major reasons for delayed healing and abnormal scarring. The development of new multifunctional dressing materials that can effectively...

Cited by 21 publications

References 45 publications

Gallium-modified gelatin nanoparticles loaded with quercetin promote skin wound healing via the regulation of bacterial proliferation and macrophage polarization

Gallium-modified gelatin nanoparticles loaded with quercetin promote skin wound healing via the regulation of bacterial proliferation and macrophage polarization

In Situ Single-Cell Bacterial Imaging Provides Mechanistic Insight into the Photodynamic Action of Photosensitizer-Loaded Hydrogels

Three‐Step Regenerative Strategy: Multifunctional Bilayer Hydrogel for Combined Photothermal/Photodynamic Therapy to Promote Drug‐Resistant Bacteria‐Infected Wound Healing

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