Large animal model of controlled peripheral artery calcification.

Abstract

Peripheral artery disease (PAD) in the lower extremity arteries leads to significant morbidity and mortality. Arterial calcification contributes to poor clinical outcomes and greatly increases the risk of amputation. Current treatments for calcific lesions are limited and yield suboptimal results. A large animal model that closely mimics calcific PAD and accommodates human-sized devices could enhance the development of safer and more effective therapies. Our objective was to create a swine model of late-stage arterial calcification to test the efficacy and side effects of surgical interventions. To induce lesions, swine received injections of CaCl₂ directly into the media and periadventitial spaces of the iliac, femoral, and popliteal arteries using a micro-needle catheter. The injection sites were varied to create eccentric and concentric lesions of differing lengths and patterns. Adjacent non-calcified arterial segments served as intersubject controls. The lesions were allowed to mature, and Computed Tomography Angiography and Intravascular Ultrasound imaging demonstrated ring-like calcification patterns and no pulsatility as early as 4 weeks after induction. Mechanical testing of excised arteries mirrored the mechanical properties of calcified human vessels, including characteristic stiffening. Histological analysis further confirmed that the calcified arteries in this model closely resembled human calcified femoropopliteal vessels, displaying inflammation, accumulation of collagen and glycosaminoglycans, elastin degradation, and smooth muscle cell loss within a degenerated tunica media. This porcine model replicates key pathological features of human calcific disease and provides a robust platform to evaluate the impacts and mechanisms of calcium-modifying treatments. STATEMENT OF SIGNIFICANCE: Arterial calcification is a key contributor to poor outcomes in peripheral artery disease (PAD). Our study presents a swine model of controlled peripheral artery calcification produced using targeted calcium chloride injections delivered endovascularly via a microneedle catheter. This approach creates arterial calcific lesions that closely replicate the mechanical, structural, and histological features of human calcified arteries. Additionally, the model accommodates human-sized devices, providing a robust platform for testing advanced biomaterials, devices, and therapies designed to modify or reverse calcification. By addressing a significant gap in preclinical research, our work aims to enhance treatment strategies for PAD, with the potential to reduce amputation rates and improve patient outcomes.