Calcium Peroxide‐Based Hydrogels Enable Biphasic Release of Hydrogen Peroxide for Infected Wound Healing

Wound infection is a major factor affecting the speed and quality of wound healing. While hydrogen peroxide (H2O2) is recognized for its antibacterial capacity and facilitation of wound healing, its administration requires careful dosage differentiation. Inappropriately matched dosages can protract the healing of infected wounds. Herein, a calcium peroxide‐based hydrogel (CPO‐Alg hydrogel) is fabricated to enable a biphasic tapered release of H2O2, ensuring robust initial antimicrobial activity followed by sustained promotion of cellular proliferation of wound healing. The design of the hydrogel allowed for the calcium peroxide nanoparticles (CPO NPs) being in two spatial niches within the gel framework. When applied to infectious wounds, CPO NPs with weak constraints are promptly released out of the gel, penetrating into infected regions to serve as antibacterial agents that eliminate bacteria and biofilms at high concentrations. Conversely, the entrapped CPO NPs structurally integrated into the gel remain confined, thus gradually degrading and allowing a mild release of H2O2 through hydrolysis in a moist environment that contributes to the cell growth in the later stage. The CPO‐Alg hydrogel represents an innovative and practical solution for the antimicrobial protection of chronic wounds, offering promising prospects for advancing wound healing. A new nanoparticulate network hydrogel is developed by employing CPO NPs as building units to cross‐link with alginate macromolecules to form the hydrogel matrix. The CPO NPs could exist in the gel framework with two different forms. Such unique structural design enables a biphasic tapered release of H2O2. The nanoparticulate network hydrogel represents an innovative solution for the antimicrobial protection of chronic wounds.