Rubidium (Rb) is
an important microelement for the human body,
which can kill and inhibit bacteria. Rubidium-containing polyhydrated
ionogens have been applied to treat refractory wounds. In this work,
for the first time, Rb was added into calcium alginate hydrogel (Rb–CA
gel) and then made into a dressing by freeze-drying. The addition
of Rb to CA maintained a well-ordered porous structure with only slightly
reduced swelling and storage modulus and increased roughness and in
vitro degradation rate. Experiments in vitro demonstrated that Rb–CA
gels could not only inhibit the growth of Staphylococcus
aureus and Pseudomonas aeruginosa ubiquitous but were nontoxic and even conducive to human umbilical
vein endothelial cells (HUVECs), fibroblasts, and keratinocytes. HUVECs
exposed to Rb–CA gels exhibited enhanced migration and tubule
formation ability, increased vascular endothelial growth factor secretion,
and improved activation of the nuclear factor (erythroid-derived 2)-like
2 (NRF2)/heme-oxygenase-1 (HO-1) signaling pathway. Rb–CA gels
also promoted the migration of fibroblasts and keratinocytes. In vivo,
in a type II diabetic male Sprague-Dawley rat wound model, neovascularization,
re-epithelialization, and collagen deposition were all improved greatly
by the Rb–CA gel, with the upregulation of NRF2 and HO-1 protein
secretion that inhibited the oxidative stress reaction in the wound
sites. Moreover, the Rb–CA gel exhibited a strong anti-inflammatory
effect on the wound. In summary, the application of Rb–CA gel
dressings to diabetic wounds could produce various synergetic enhancements
in terms of angiogenesis, re-epithelialization, and collagen deposition.
Hence, Rb–CA gels can be used as a novel therapeutic strategy
to promote the healing of diabetic wounds.