Abstract
Peripheral arterial disease (PAD) poses a global health challenge, particularly in its advanced stages known as critical limb ischemia (CLI). Conventional treatments often fail to achieve satisfactory outcomes. Patients with CLI face high rates of morbidity and mortality, underscoring the urgent need for innovative therapeutic strategies. Recent advancements in biomaterials and biotechnology have positioned biomaterial-based vascularization strategies as promising approaches to improve blood perfusion and ameliorate ischemic conditions in affected tissues. These materials have shown potential to enhance therapeutic outcomes while mitigating toxicity concerns. This work summarizes the current status of PAD and highlights emerging biomaterial-based strategies for its treatment, focusing on functional genes, cells, proteins, and metal ions, as well as their delivery and controlled release systems. Additionally, the limitations associated with these approaches are discussed. This review provides a framework for designing therapeutic biomaterials and offers insights into their potential for clinical translation, contributing to the advancement of PAD treatments.