4.8 Article

Clickable and smart drug delivery vehicles accelerate the healing of infected diabetic wounds

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 350, Issue -, Pages 613-629

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2022.08.053

Keywords

Amino-yne click reaction; Environmentally-responsive hydrogel; Smart drug delivery; Diabetic wound healing

Funding

  1. National Natural Science Foundation of China [8220090789]
  2. China Postdoctoral Science Foundation [2021M702349]
  3. 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZYJC21026, ZYJC21077, ZYJC18023]
  4. Fundamental Research Funds for the Central Universities [2022SCU12062]

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A multi-functional hydrogel based on hyaluronic acid was synthesized through a click reaction, showing antibacterial, anti-inflammatory, and pro-angiogenic properties. The hydrogel encapsulated nanoparticles with a smart drug release profile and effectively facilitated the healing of infected wounds in vivo.
In this study, an adipic acid dihydrazide (ADH)/ tannic acid (TA)-grafted hyaluronic acid (HA)-based multi-functional hydrogel was synthesized through a spontaneous aminoyne click reaction and used to promote the improved healing of infected diabetic wounds. This hydrogel exhibited a range of beneficial properties such as tunable gelation time, adjustable mechanical properties, pH-sensitive response characteristics, excellent inject -ability, the ability to readily adhere to tissue, and ultra-intimate contact capabilities. Following the encapsulation of ultrasmall Ag nanoclusters (AgNCs) and deferoxamine loaded polydopamine/ hollow mesoporous manganese dioxide (PHMD, PDA/H-mMnO(2)@DFO) nanoparticles, the prepared hydrogel presented with robust antibacterial, anti-inflammatory, and pro-angiogenic properties and a desirable smart drug release profile. In this fabricated platform, PHMD was able to effectively alleviate localized oxidative stress and prolonged oxygen deprivation via the decomposition of endogenous H(2)O(2 )to produce O-2. Further in vivo assays revealed that this hydrogel was capable of facilitating the healing of infected wounds through the sequential engagement of antibacterial, anti-inflammatory, and pro-angiogenic activities. Together, this synthesized clickable environmentally-responsive hydrogel offers great promise as a tool that can be applied to aid in the healing of chronically infected diabetic wounds and other inflammatory conditions.

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