Calcium Hydride‐Based Dressing to Promote Wound Healing

Abstract

Wound microenvironment with excess reactive oxygen species (ROS) can significantly inhibit wound healing. Encouraged by hydrogen molecules (H 2 ) with effective ROS scavenging and calcium hydride (CaH 2 ) with sufficient H 2 supply, the authors for the first time employed CaH 2 as a therapeutic H 2 donor and starch as a diluent to construct CaH 2 pulvis dressing for wound healing treatment. It has been found that CaH 2 by generating H 2 exhibited excellent ROS scavenging performance, favorable for preserving the oxidative-stress-induced cell death. After being applied onto the skin wound, the CaH 2 pulvis dressing with the unique ROS-scavenging ability can accelerate skin wound healing in healthy/diabetic mice (small animal models) and Bama mini-pigs (large animal model). Such CaH 2 dressing can release H 2 to relieve the inflammation levels, decrease the secretion of pro-inflammatory cytokines, increase the infiltration of inflammation-suppressive immune cells, and promote the regeneration of new blood vessels and collagens, thereby accelerating wound healing. This work highlighted that the integration of anti-oxidation and anti-inflammation functions based on CaH 2 dressing endowed it with a promising possibility for the treatment of inflammatory diseases.

Recent Advances in Metal-Hydride-Based Disease Treatment

“…Hydrogen can reduce hydroxyl radicals to H 2 O, selectively scavenging free radicals while retaining other essential substances of ROS for normal signaling regulation . Inspired by this, several metal hydrides have been developed for the treatment of a variety of diseases related to inflammation, including diet-induced non-alcoholic fatty liver disease, Alzheimer’s disease, atherosclerosis, acute respiratory distress syndrome, and wound healing . As early as 2016, Hou and co-workers prepared coral calcium hydride to alleviate diet-induced non-alcoholic fatty liver disease by generating hydrogen from coral calcium hydride to scavenge ROS and prevent mitochondrial decay, resulting in the improvement of metabolic syndrome in patients and animal models .…”

“…The use of metal hydride for disease treatment originated from an attempt by Long’s group . The gratifying treatment of use for diet-induced non-alcoholic fatty liver disease attracted further attention on using metal hydride for the treatment of Alzheimer’s disease, atherosclerosis, acute respiratory distress syndrome, wound healing, , and cancer . In the course of development, the role of metal hydride in disease treatment is no longer limited to in situ hydrogen delivery vehicles, and its intrinsic photothermal conversion, acoustic imaging, and release of metal ion have also been fully exploited to further strengthen disease treatment .…”

“…In the course of development, the role of metal hydride in disease treatment is no longer limited to in situ hydrogen delivery vehicles, and its intrinsic photothermal conversion, acoustic imaging, and release of metal ion have also been fully exploited to further strengthen disease treatment . Overall, a range of metal hydrides have been developed for disease treatment, including calcium hydride (CaH 2 ), magnesium hydride (MgH 2 ), palladium hydride (PdH), and titanium hydride (TiH 1.924 ) . The astonishing treatment efficiency of these metal hydrides in animal models and metal hydride as a generic nanomedicine capable of treating a wide range of diseases implies that more attention and investment should be given to metal hydrides in the future.…”

Biomaterials for immunomodulation in wound healing

“…Reproduced with permission Gong et al . [ 198 ]. ( D ) Schematic illustration of photo-induced crosslinking mechanism for tissue integration of hydrogel and PLGA-NB capsules and ( E ) representative images of rabbit ear skin wound healing and scar formation in differently treated groups.…”

“…Gong et al . created a CaH 2 pulvis dressing capable of suppressing the secretion of pro-inflammatory cytokines and promoting the infiltration of Treg cells [ 198 ] ( Figure 6C ). The incorporation of checkpoint inhibitors and co-stimulatory molecules into biomaterials represents another strategy to modulate T-cell activation and function.…”