Two-Dimensional Mg2 Si Nanosheet-Enabled Sustained Hydrogen Generation for Improved Repair and Regeneration of Deeply-Burned Skin

Unexpected temporal and spatial extension of inflammation in severely burned patients frequently causes cellular Apoptosis, wound deepening, and serious fibroplasia, leading to the difficulty of wound healing and the formation of hypertrophic scar. Molecular hydrogen holds a high potential for wound healing owing to its anti-inflammatory effect and high biosafety, but commonly used hydrogen administration routes hardly achieve the sustained supply of high-dosage hydrogen, limiting hydrogen therapy efficacy. Here, a new type of two-dimensional metal silicide (MSene), Mg₂ Si nanosheet (MSN), is exploited as a super-persistent hydrogen-releasing nanomaterial with high biocompatibility, and the incorporation of MSN into the chitosan/hyaluronic acid hydrogel (MSN@CS/HA) is developed as a wound dressing to repair deeply burned skin. The MSN@CS/HA hydrogel dressing can continuously generate a large number of hydrogen molecules for about one week in the physiological conditions in support of local, continuous, long-term, and plentiful hydrogen supply at the burned site and remarkably promotes the healing and regeneration of deep second-degree and three-degree burn wounds without visible scar and toxic side effect. Mechanistically, a locally sustained supply of hydrogen molecules induces anti-inflammatory M2 macrophage polarization in time by enhancing CCL2 (chemokine C-C motif ligand 2) expression to promote angiogenesis and reduce fibrosis and also enhances the proliferation and migration capability of skin cells directly and indirectly by locally scavenging over-expressed Reactive Oxygen Species (ROS), synergistically favoring wound repair. The proposed synthesis method, therapeutic strategy, and mechanisms will open a window for synthesizing a variety of MSene nanomaterials and developing their various pro-angiogenesis applications besides wound healing. This article is protected by copyright. All rights reserved.

hydrogen therapy; skin regeneration; sustained release; wound dressing; wound healing.