4.8 Article

An all-in-one CO gas therapy-based hydrogel dressing with sustained insulin release, anti-oxidative stress, antibacterial, and anti-inflammatory capabilities for infected diabetic wounds

Journal

ACTA BIOMATERIALIA
Volume 146, Issue -, Pages 49-65

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2022.04.043

Keywords

CO gas therapy; Anti-oxidative stress; Antibacterial; Anti-inflammatory; Diabetic wounds

Funding

  1. Zhejiang Public Welfare Sci-ence and Technology Project [LGF22E030010]
  2. Medicine and Health Science and Technology Plan Projects in Zhejiang province [2022RC212]
  3. Priority Academic Program Development of Jiangsu Higher Education Institutions

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A versatile hydrogel dressing has been developed for the treatment of diabetic wounds. This dressing can regulate blood glucose, anti-oxidative stress, antibacterial and anti-inflammatory. It has good tissue adhesion, injectability and self-healing properties, and can sustainably release insulin and generate CO in inflamed wound tissue. The dressing significantly promotes the healing of diabetic wounds and has excellent biocompatibility.
To effectively treat diabetic wounds, the development of versatile medical dressings that can long-term regulate blood glucose and highly effective anti-oxidative stress, antibacterial and anti-inflammatory are critical. Here, an all-in-one CO gas-therapy-based versatile hydrogel dressing (ICOQF) was developed via the dynamic Schiff base reaction between the amino groups on quaternized chitosan (QCS) and the aldehyde groups on benzaldehyde-terminated F108 (F108-CHO) micelles. CORM-401 (an oxidant-sensitive COreleasing molecules) was encapsulated in the hydrophobic core of F108-CHO micelles and insulin was loaded in the three-dimensional network structure of ICOQF. The dynamic Schiff base bonds not only endowed ICOQF with good tissue adhesion, injectability and self-healing, but also gave it sustained and controllable insulin release ability. In addition, ICOQF could quickly generate CO in inflamed wound tissue by consuming reactive oxygen species. The generated CO could effectively anti-oxidative stress by activating the expression of heme oxygenase; antibacterial by inducing the rupture of bacterial cell membranes and mitochondrial dysfunction and inhibiting the synthesis of adenosine triphosphate; and anti-inflammatory by inhibiting the proliferation of activated macrophages and promoting the polarization of the M1 phenotype to the M2 phenotype. Due to these outstanding properties, ICOQF significantly promoted the healing of STZ-induced MRSA -infected diabetic wounds accompanied by good biocompatibility. This study clearly shows that ICOQF is a versatile hydrogel dressing with great application potential for the management of diabetic wounds.

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