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

Abstract

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-mMnO2@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 H2O2 to produce O2. 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.