期刊
MATERIALS TODAY NANO
卷 17, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.mtnano.2021.100164
关键词
Micelle; Tissue microenvironment; Polythioketal; Nanoparticles; Viscosupplementation
资金
- National Key Research and Development Program of China [2017YFE0117700]
- Fundamental Research Funds for the Central Universities of China [2020XZZX004-01]
This study developed a multifunctional injectable hydrogel system for treating osteoarthritis by depleting ROS and suppressing inflammation, significantly alleviating OA symptoms and preventing degradation of cartilage extracellular matrix.
Selective exhaustion of over-expressed reactive oxygen species (ROS) is of great significance in the therapy of osteoarthritis (OA) because of the inhibiting effect on oxidative stress and inflammation. Herein, a ROS-scavenging and drug-release platform was prepared via encapsulating dexamethasone acetate (DA)-loaded ROS erasable poly(ethylene glycol)-b-polythioketal-b-poly(ethylene glycol) (PEG-PTK-PEG) micelles (PDM) into an injectable hydrogel. The hydrogel (HDH@PDM) was constructed by Schiff base reaction between hydrazide-grafted hyaluronic acid (HA-ADH) and aldehyde-modified dextran (Dex-ALH), achieving a self-healing property for viscosupplementation. The PDM imparted enhanced antioxidant capability to the hydrogel, which, in turn, endowed the PDM with prolonged retention and sustained DA release. The intraarticularly administered multifunctional injectable hydrogel potently diminished inflammation via depleting ROS and suppressing inflammatory cytokines, as well as downregulating pro-inflammatory M1 macrophages ratio in a rat OA model. The developed therapeutic system significantly alleviated OA symptoms, embodying the excellent capability of preventing cartilage extracellular matrix degeneration with negligible toxicity in vivo. (C) 2021 Elsevier Ltd. All rights reserved.
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