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Despite ongoing progress in stent technology and deployment techniques, in-stent restenosis (ISR) still remains a major issue following percutaneous coronary intervention (PCI) and accounts for 10.6% of all interventions in the United States. With the continuous rise in ISR risk factors such as obesity and diabetes, along with an increase in the treatment of complex lesions with high-risk percutaneous coronary intervention (CHIP), a substantial growth in ISR burden is expected. This review aims to provide insight into the mechanisms, classification, and management of ISR, with a focus on exploring innovative approaches to tackle this complication comprehensively, along with a special section addressing the approach to complex calcified lesions.

In the treatment of atherosclerotic disease patients, the adoption of second-generation drug-eluting stents (DES) in percutaneous coronary intervention reduced the occurrence of in-stent restenosis (ISR) and acute stent thrombosis (ST) when compared to bare metal stents and 1st generation DES. However, the permanent encaging of the vessel wall by any of the metallic stents perpetuates the inflammation process and prevents vasomotion in the treated segment. Aiming to overcome this issue, the bioresorbable scaffold (BRS) concept was developed by providing transient vascular radial support to the target segment during the necessary time to heal and disappearing after a period of time. Close to 20 years since BRS technology was first reported, the interventional cardiology field saw the rise and fall of several BRS devices. Although iron-based BRS is an emerging technology, currently, magnesium-alloy resorbable scaffolds devices are supported with the most robust data. This manuscript aims to review the concept of magnesium-based BRS devices, as well as their bioresorption mechanisms and the status of this technology, and the clinical outcomes of patients treated with magnesium BRS and to review the available evidence on iron-based BRS technology.