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Sandwich-structure hydrogels implement on-demand release of multiple therapeutic drugs for infected wounds.

ABSTRACT: Wound infections bring huge challenges to clinical practice. A series of approaches are involved in the management of infected wounds including use of antibacterial agents, granulation tissue regeneration and scar prevention. In this study, we fabricated a sandwich-structure hydrogel dressing through layer-by-layer assembly of films and hydrogels. By pre-loading silver nanoparticles (AgNPs), vascular endothelial growth factors (VEGF) and ginsenoside Rg3 (Rg3) into each layer of the sandwich compound, this hydrogel could realize the sequential release of these drugs onto infected wound beds as demanded. Moreover, altering the thickness of middle layer could further change the drug delivery patterns characterized by delay at the initial releasing timepoint. When applying this dressing on infected wounds of rabbit ears, we found it could alleviate infection-induced inflammation, promote granulation tissue regeneration and inhibit scar formation. Collectively, the design of sandwich-structure hydrogels was facilitated to deliver specific drugs sequentially during their therapeutic time window for complicated diseases and has shown potential applications in infected wounds.

SUBMITTER: Zheng T

PROVIDER: S-EPMC9076599 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Sandwich-structure hydrogels implement on-demand release of multiple therapeutic drugs for infected wounds.

Zheng Tao T Huang Jinjian J Jiang Yungang Y Tang Qinqing Q Liu Ye Y Xu Ziyan Z Wu Xiuwen X Ren Jianan J

RSC advances 20191220 72

Wound infections bring huge challenges to clinical practice. A series of approaches are involved in the management of infected wounds including use of antibacterial agents, granulation tissue regeneration and scar prevention. In this study, we fabricated a sandwich-structure hydrogel dressing through layer-by-layer assembly of films and hydrogels. By pre-loading silver nanoparticles (AgNPs), vascular endothelial growth factors (VEGF) and ginsenoside Rg3 (Rg3) into each layer of the sandwich comp ...[more]

PMID: 35542841

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Project description:Bacterial infection, complex wound microenvironment and persistent inflammation cause delayed wound healing and scar formation, thereby disrupting the normal function and appearance of skin tissue, which is one of the most problematic clinical issues. Although Ag NPs have a strong antibacterial effect, they tend to oxidize and form aggregates in aqueous solution, which reduces their antibacterial efficacy and increases their toxicity to tissues and organs. Current research on scar treatment is limited and mainly relies on growth factors and drugs to reduce inflammation and scar tissue formation. Therefore, there is a need to develop methods that effectively combine drug delivery, antimicrobial and anti-inflammatory agents to modulate the wound microenvironment, promote wound healing, and prevent skin scarring. Herein, we developed an innovative Ag nanocomposite hydrogel (Ag NCH) by incorporating Ag nanoparticles (Ag NPs) into a matrix formed by linking catechol-modified hyaluronic acid (HA-CA) with 4-arm PEG-SH. The Ag NPs serve dual functions: they act as reservoirs for releasing Ag/Ag+ at the wound site to combat bacterial infections, and they also function as cross-linkers to ensure the sustained release of basic fibroblast growth factor (bFGF). The potent antibacterial effect of the Ag NPs embedded in the hydrogel against S.aureus was validated through comprehensive in vitro and in vivo analyses. The microstructural analysis of the hydrogels and the in vitro release studies confirmed that the Ag NCH possesses smaller pore sizes and facilitates a slower, more sustained release of bFGF. When applied to acute and infected wound sites, the Ag NCH demonstrated remarkable capabilities in reshaping the immune and regenerative microenvironment. It induced a shift from M1 to M2 macrophage polarization, down-regulated the expression of pro-inflammatory factors such as IL-6 and TNF-α, and up-regulated the expression of anti-inflammatory IL-10. Furthermore, the Ag NCH played a crucial role in regulating collagen deposition and alignment, promoting the formation of mature blood vessels, and significantly enhancing tissue reconstruction and scarless wound healing processes. We think the designed Ag NCH can provide a promising therapeutic strategy for clinical applications in scarless wound healing and antibacterial therapy.

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Sandwich-structure hydrogels implement on-demand release of multiple therapeutic drugs for infected wounds.

Publications

Sandwich-structure hydrogels implement on-demand release of multiple therapeutic drugs for infected wounds.

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