Traumatic injuries typically lead to severe wounds which are accompanied by excessive hemorrhage. Although various hemostatic wound dressings have been developed, there is an ongoing need for advanced materials that combine both hemostatic and therapeutic abilities for effective wound management. Cryogels, an emerging class of wound-dressing materials, have garnered significant attention because of their enhanced mechanical properties, blood and wound exudates absorption abilities that improve the hemoconcentration, and substantial porosities that facilitate the infiltration of host cells and tissues, all of which contribute to improved wound healing. Growing evidence has demonstrated that oxygen-generating materials promote wound healing, including angiogenesis, by inducing hyperoxic oxidative stress. Here, a new type of oxygen-generating cryogel (Oxycryogel) is fabricated by lyophilizing oxygen-generating hydrogels formed by a calcium peroxide (CaO2)-mediated crosslinking reaction, which resulted in interconnected macroporous structures with reinforced mechanical properties compared to that of hydrogel formulations. The Oxycryogels developed in this study demonstrate superior blood absorption capabilities and calcium ion (Ca2+) production by CaO2 decomposition. Additionally, blood clot formation is improved through hemoconcentration and Ca2+-mediated coagulation cascades in vitro. Furthermore, the oxygen-releasing kinetics are modulated by adjusting the CaO2 concentration and are further promoted using a catalase solution. The Oxycryogels provide transient hyperoxic conditions in vitro and in vivo, facilitating wound healing, such as angiogenesis and wound closure through the synergistic effects of porosity, hemostatic ability, and hyperoxic oxidative stress in vivo. In conclusion, the Oxycryogels developed here have great potential as advanced oxygen-delivery and hemostatic materials for wound healing and management. Graphical abstract Oxygen-generating gelatin-based cryogels (Oxycryogels), a new type of wound dressing integrating hemostasis and wound healing, are developed through lyophilization and calcium peroxide (CaO2)-mediated reactions. CaO₂ provides oxygen for angiogenesis and calcium ions for blood coagulation, while the strong blood absorption of Oxycryogels enhances hemoconcentration, collectively facilitating effective skin wound healing.

Oxygen-generating gelatin-based cryogels for enhanced hemostasis and skin wound healing

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发表日期：

2025年2月19日

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Sol Kim,
Jeon Il Kang,
Kyung Min Park

摘要

Traumatic injuries typically lead to severe wounds which are accompanied by excessive hemorrhage. Although various hemostatic wound dressings have been developed, there is an ongoing need for advanced materials that combine both hemostatic and therapeutic abilities for effective wound management. Cryogels, an emerging class of wound-dressing materials, have garnered significant attention because of their enhanced mechanical properties, blood and wound exudates absorption abilities that improve the hemoconcentration, and substantial porosities that facilitate the infiltration of host cells and tissues, all of which contribute to improved wound healing. Growing evidence has demonstrated that oxygen-generating materials promote wound healing, including angiogenesis, by inducing hyperoxic oxidative stress. Here, a new type of oxygen-generating cryogel (Oxycryogel) is fabricated by lyophilizing oxygen-generating hydrogels formed by a calcium peroxide (CaO₂)-mediated crosslinking reaction, which resulted in interconnected macroporous structures with reinforced mechanical properties compared to that of hydrogel formulations. The Oxycryogels developed in this study demonstrate superior blood absorption capabilities and calcium ion (Ca²⁺) production by CaO₂ decomposition. Additionally, blood clot formation is improved through hemoconcentration and Ca²⁺-mediated coagulation cascades in vitro. Furthermore, the oxygen-releasing kinetics are modulated by adjusting the CaO₂ concentration and are further promoted using a catalase solution. The Oxycryogels provide transient hyperoxic conditions in vitro and in vivo, facilitating wound healing, such as angiogenesis and wound closure through the synergistic effects of porosity, hemostatic ability, and hyperoxic oxidative stress in vivo. In conclusion, the Oxycryogels developed here have great potential as advanced oxygen-delivery and hemostatic materials for wound healing and management.

Graphical abstract

Oxygen-generating gelatin-based cryogels (Oxycryogels), a new type of wound dressing integrating hemostasis and wound healing, are developed through lyophilization and calcium peroxide (CaO₂)-mediated reactions. CaO₂ provides oxygen for angiogenesis and calcium ions for blood coagulation, while the strong blood absorption of Oxycryogels enhances hemoconcentration, collectively facilitating effective skin wound healing.