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

In this study, an adipic acid dihydrazide (ADH)/ tannic acid (TA)-grafted hyaluronic acid (HA)-based multifunctional hydrogel was synthesized through a spontaneous amino-yne 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 injectability, 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.