ABSTRACT Ischemic wounds remain a major challenge in clinical management due to restricted blood flow, poor oxygen delivery, chronic inflammation, and impaired angiogenesis, which collectively delay healing. A critical regulator of wound repair, the PI3K/AKT/mTOR pathway, supports cell survival, proliferation, and angiogenesis, but is down‐regulated under ischemic conditions. To address this, nanotechnology offers promising strategies, particularly through zinc and copper nanoparticles, which have shown potential in modulating this pathway to accelerate repair. This review highlights thermally synthesized zinc–copper nanoparticles produced via green chemistry and phytochemical‐assisted green synthesis as dual approaches that ensure biocompatibility, stability, and enhanced biological performance, with particular emphasis on the role of physicochemical properties and green synthesis chemistry. These nanoparticles exhibit antioxidant and antibacterial activities, crucial for mitigating oxidative stress and infection in ischemic wounds. Furthermore, they stimulate endothelial cell proliferation, promote angiogenesis, and indirectly enhance tissue regeneration by activating the PI3K/AKT/mTOR pathway. Despite their therapeutic promise, translation to clinical use faces challenges, including large‐scale synthesis, stability, and safety validation. This review underscores strategies to overcome these barriers while maximizing nanoparticle efficiency. Overall, green‐synthesized zinc–copper nanoparticles represent a sustainable and effective platform for developing ischemic wound healing models, offering new prospects in targeted, eco‐friendly wound care management.
Mendonce et al. (Wed,) studied this question.