Thermosensitive Hydrogel Loaded with Nickel–Copper Bimetallic Hollow Nanospheres with SOD and CAT Enzymatic-Like Activity Promotes Acute Wound Healing

Abstract

Various injury defense and repair functions are performed by the skin. Free radicals secreted after injury cause oxidative stress and inflammatory responses, which make wound healing difficult. However, the current metal nanomaterials for wound repair do not have sufficient catalytic activity or complex material design and cannot properly fit wounds. Therefore, it is imperative to develop more effective therapeutic approaches. This study investigated the effect of Ni 4 Cu 2 hollow nanospheres composited with F127 hydrogel on promoting wound healing by applying them to wounds. Ni 4 Cu 2 hollow nanospheres exhibited a superior spatial structure, contained many catalytic sites, and could be synthesized in a simple manner. In vitro experiments showed that Ni 4 Cu 2 hollow nanospheres had superoxide dismutase-like activity and promoted fibroblast migration, angiogenesis, and macrophage polarization. F127, which is a thermosensitive, nontoxic, phase-change and porous hydrogel material, has proven to be an effective choice for injectable and sprayable medical dressings. Ni 4 Cu 2 hollow nanospheres were mixed with F127 hydrogel without significantly affecting its performance. In addition to adapting to the complex, irregular gaps of acute wounds, the mixture lengthened the nanozyme release time, which enhanced healing. Based on the animal experiments, the Ni 4 Cu 2 /F127 composite hydrogel effectively promoted wound healing, epithelial regeneration, and the formation of skin appendages such as hair follicles in mice. Furthermore, the Ni 4 Cu 2 /F127 composite hydrogel was nontoxic to animals and had high biological safety. The Ni 4 Cu 2 /F127 composite hydrogel has provided an innovative strategy to develop composite hydrogels for the treatment of acute skin wounds.

Modulation of Macrophage Function by Bioactive Wound Dressings with an Emphasis on Extracellular Matrix-Based Scaffolds and Nanofibrous Composites

“…Puertas-Bartolomé et al fabricate a catechol-bearing NPs hydrogel and demonstrate that it possesses excellent wound healing capacities, including the regulation of ROS production, an anti-inflammatory response, and the upregulation of VEGF expression [ 117 ]. Similarly, Ni 4 Cu 2 hollow nanospheres, applied in combination with F127 hydrogel, were found to effectively promote wound healing, epithelial regeneration, and the formation of hair follicles in mice [ 118 ]. Moreover, Zhu et al prepared an injectable hydrogel containing substance P-loaded NPs, which showed excellent wound-healing efficacy by promoting an early inflammatory response and the subsequent M2 macrophage polarization in full-thickness wounds [ 119 ].…”

Photodynamic Alginate Zn-MOF Thermosensitive Hydrogel for Accelerated Healing of Infected Wounds

“…Hydrogels are three-dimensional (3D) networks formed by cross-linking hydrophilic polymer chains, which are similar to extracellular matrix (ECM) and can provide a moist environment to promote wound healing. , In particular, thermosensitive hydrogels can be applied to different desired wound shapes at body temperature . Alginate is a natural polysaccharide derived from brown seaweed, which can increase the moisturizing effect and improve the mechanical properties of thermosensitive hydrogels .…”

“…26,27 In particular, thermosensitive hydrogels can be applied to different desired wound shapes at body temperature. 28 Alginate is a natural polysaccharide derived from brown seaweed, which can increase the moisturizing effect and improve the mechanical properties of thermosensitive hydrogels. 29 Thus, alginate-based thermosensitive hydrogel is a promising biomaterial for wound dressings.…”

“…22 F127 can form a thermosensitive hydrogel at low temperatures, which can promote the application of Ce6@MOF in wounds of different shapes at body temperature. 28 A thermosensitive Ce6@MOF-Gel was obtained by combining Ce6@MOF and alginate with F127 (Scheme 1a). We hypothesized that Ce6@ MOF-Gel could improve the antibacterial and wound healing efficacy by producing ROS without drug resistance (Scheme 1b).…”

“…Zinc ions can damage bacterial cell membranes and load Ce6 into MOF through strong electrostatic interactions . F127 can form a thermosensitive hydrogel at low temperatures, which can promote the application of Ce6@MOF in wounds of different shapes at body temperature . A thermosensitive Ce6@MOF-Gel was obtained by combining Ce6@MOF and alginate with F127 (Scheme a).…”