The most common socioeconomic healthcare issues in clinical are burns, surgical incisions and other skin injuries. Skin lesion healing can be achieved with nanomedicines and other drug application techniques. This study developed a nano-spray based on cross-linked amorphous calcium peroxide (CaO) nanoparticles of polyacrylic acid (PAA) for treating skin wounds (PAA-CaO nanoparticles). CaO serves as a 'drug' precursor, steadily and continuously releasing calcium ions (Ca) and hydrogen peroxide (HO) under mildly acidic conditions, while PAA-CaO nanoparticles exhibited good spray behavior in aqueous form. Tests demonstrated that PAA-CaO nanoparticles exhibited low cytotoxicity and allowed L929 cells proliferation and migration . The effectiveness of PAA-CaO nanoparticles in promoting wound healing and inhibiting bacterial growth was assessed in SD rats using full-thickness skin defect and ()-infected wound models based thereon. The results revealed that PAA-CaO nanoparticles demonstrated significant advantages in both aspects. Notably, the infected rats' skin defects healed in 12 days. The benefits are linked to the functional role of Ca coalesces with HO as known antibacterial and healing-promoted agents. Therefore, we developed nanoscale PAA-CaO sprays to prevent bacterial development and heal skin lesions.