Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. H2 has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how H2 functions in wound healing remains unknown, especially for the link between H2 and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of H2 (66% H2) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of H2 (66% H2) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on O2 or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the H2 group. ECM components early (3 days post-wounding) deposition were found in the H2 group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. H2 accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between H2 and ECM deposition and EpSCs activation. These H2-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life.

BACKGROUND Patients with keloids who receive radiotherapy (RT) after surgery can develop refractory wounds that cannot be healed by the patient's own repair system. Such chronic wounds are uneven and complex due to persistent abscess and ulceration. Without external intervention, they can easily result in local tissue necrosis or, in severe cases, large area tissue resection, amputation, and even death. CASE SUMMARY This article describes the use of hydrogen to treat a 42-year-old female patient with a chronic wound on her left shoulder. The patient had a skin graft that involved implanting a dilator under the skin of her left shoulder, and then transferring excess skin from her shoulder onto scar tissue on her chest. The skin grafting was followed by two rounds of RT, after which the shoulder wound had difficulty healing. For six months, the patient was treated with 2 h of hydrogen inhalation (HI) therapy per day, in addition to application of sterile gauze on the wound and periodic debridement. We also performed one deep, large, sharp debridement to enlarge the wound area. The wound healed completely within 6 mo of beginning the HI treatment. CONCLUSION After HI therapy, the patient showed superior progress in reepithelialization and wound repair, with eventual wound closure in 6 mo, in comparison with the previous failures of hyperbaric oxygen and recombinant bovine basic fibroblast growth factor therapies. Our work showed that HI therapy could be a new strategy for wound healing that is cleaner, more convenient, and less expensive than other therapies, as well as easily accessible for further application in clinical wound care.

Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. H2 has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how H2 functions in wound healing are still obscure. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of H2 (66% H2) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of H2 (66% H2) greatly increased the healing rate (3 times higher than the control group) on day 11 post wounding. The effect was not dependent on O2 or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the H2 group. Extracellular matrix components early (3 days post wounding) deposition were found in the H2 group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. H2 accelerated early autologous epidermal stem cell proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. These H2-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life.