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

Abstract

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 <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> 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.