Rubidium-Containing Calcium Alginate Hydrogel for Antibacterial and Diabetic Skin Wound Healing Applications

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.