Artificial multienzyme nanoflower composite hydrogel for efficiently promoting MRSA-infected diabetic wound healing via glucose-activated NO releasing and microenvironment regulation

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2025-03-22 DOI:10.1016/j.bioactmat.2025.03.014

Hui Ma , Yuanhao Luo , Yifu Wang , Yi Hao , Jinjin Li , Xiaolan Gao , Yamin Xiong , Leiliang He

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引用次数: 0

Abstract

Diabetic wound repair is a global challenge due to bacterial infection and the typical microenvironments of hyperglycemia, high pH value, hypoxia, persistent inflammation and insufficient angiogenesis. Herein, a glucose-activated nitric oxide (NO) releasing and microenvironment regulation hydrogel dressing (COH-GB) has been developed for efficiently promoting infectious diabetic wound healing. Specifically, an artificial multienzyme nanoflower (GB nanoflower) composed of glucose oxidase (GOx) and hemoglobin (Hb) was synthesized and incorporated into the hydrogel formed by carboxymethyl chitosan (CMCS), oxidized sodium alginate (OSA) and hydroxyurea (HU). In which, the hyperglycemia-triggered cascade reaction could consume glucose, while providing hydrogen peroxide (H₂O₂) for the generation of NO by HU in the presence of Hb with peroxidase-mimicking activity. The COH-GB hydrogel with essential wound dressing characteristics could remodel the microenvironment of diabetic wounds by reducing local glucose and pH levels, alleviating hypoxia, and scavenging excessive ROS; and releasing NO under different blood glucose levels for antibacterial or angiogenesis. Importantly, the prepared COH-GB hydrogel significantly accelerated the MRSA-infected diabetic wound healing by effectively reducing wound infection, inhibiting inflammation, and promoting collagen deposition, angiogenesis and the migration and differentiation of fibroblasts and keratinocytes. Notably, the formation of GB nanoflowers could enhance the activity and stability of enzymes, and improve the cascade reaction efficiency, thereby inducing a more efficient performance in microenvironment regulation, antibacterial and angiogenesis, as well as wound healing. Hence, the prepared artificial multienzyme nanoflower composite hydrogel provides an efficient and secure dressing for promoting infectious diabetic wound healing via glucose-activated NO releasing and microenvironment regulation.

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.