ZIF-8-based nanomaterials for diabetic wound healing: mechanisms, applications, and future perspectives

Diabetic wounds are a significant clinical challenge. Their complex pathophysiology involves chronic inflammation, bacterial infections, impaired angiogenesis, and oxidative stress. Traditional treatments often fail to address these interconnected issues. Recent advancements in nanotechnology highlight the potential of zeolitic imidazolate framework-8 (ZIF-8) as a versatile platform for these challenges. ZIF-8, a metal-organic framework (MOF), has unique properties like controlled drug release, antibacterial activity, immunomodulation, and antioxidant effects. These features make it an ideal candidate for diabetic wound healing. This review comprehensively examines the mechanisms by which ZIF-8-based systems promote wound healing. We explore its roles in antibacterial action, regulation of key signaling pathways involved in macrophage polarization, angiogenesis promotion, and oxidative stress reduction. We also discuss integrating ZIF-8 into various delivery systems, such as hydrogels, microneedles, and nanocomposites, and their performance in preclinical models. Despite promising results, challenges in biocompatibility, scalability, controlled release, and clinical translation remain. This review highlights these limitations and proposes future directions for optimizing ZIF-8-based therapies. By addressing these hurdles, ZIF-8 could revolutionize diabetic wound management and improve patient outcomes.