Narrative review of chronic total occlusion composition to develop biomimetic models of chronic limb-threatening ischemia to enhance revascularization strategies

Objective: Peripheral artery disease (PAD) affects >200 million people worldwide and is a chronic vascular disease characterized by impaired blood flow to the lower limbs. Chronic limb-threatening ischemia (CLTI) is the most advanced form of PAD with chronic pain at rest owing to chronic total occlusions (CTOs) within the arteries of the lower limbs. This review explores the composition of CTOs and revascularization strategies being used to treat CLTI and highlights the importance of biomimetic models to enhance revascularization strategies. Methods: A review of literature on CTOs, revascularization strategies, and biomimetic CTO analogues in PAD and CLTI using PubMed databases was performed in December 2023 through to June 2024. We included studies that evaluated the composition of CTOs and that evaluated safety, efficacy, and mortality in adults undergoing revascularization interventions. Results: Studies in the CLTI literature suggest that CTOs consist of lipid, fibrous, and calcium components, which significantly impede or obstruct blood flow to the affected limbs. Revascularization is the first-line treatment to restore blood flow to the lower limbs, by crossing or bypassing CTOs, thereby preventing amputations or death. However, current revascularization approaches are often ineffective when attempting to cross large, complex, multimaterial CTOs and require significant improvement. Conclusions: To do this, a comprehensive understanding of peripheral CTO composition and positioning is required. From this, realistic arterial models containing biomimetic lipid, fibrotic and calcific CTO analogues can be created to aid in the creation and development of devices capable of successfully crossing CTOs to improve revascularization outcomes.