A Comprehensive Review: Plaque Targeted Implantable Therapies in Atherosclerosis

Atherosclerotic cardiovascular disease (CVD) is one of the most significant global health problems today. Current standard therapies for cardiovascular disease and revascularization do not eliminate plaque locally nor alleviate residual risk of developing future cardiovascular events. Implantable cell-based therapeutic approaches provide a method for delivering therapeutic cells/cell-derived products directly to the plaque, increasing local retention and limiting systemic side effects from these therapies. This review discusses advances in bioengineered vascular interfaces and delivery technologies and immune-metabolically-mediated modulation of atherosclerotic plaque to establish a framework of precision implantable therapies. The approaches outlined in this review regulate macrophage polarization, smooth muscle cell phenotype, and endothelial repair to stabilize and reduce plaque size. Engineered exosomes and biomimetic nanovesicles are two approaches enhancing the targeting and effectiveness of precision implantable therapies. Clinical trials have demonstrated good safety and moderate effectiveness for implantable cell-based therapies used for peripheral and coronary artery disease, highlighting the need to establish biomarkers that can guide identification and selection of appropriate patients for treatment and to optimize delivery of these therapies. Several systemic factors, including but not limited to age, diabetes, and clonal haematopoiesis may affect integration of implanted cells within the atherosclerotic plaque and patient outcomes and demonstrate the value of considering both systemic elements as well as implant design in future development of implantable cell-based therapeutic modalities. Future directions emphasize, there is a need to establish standardized methods for evaluation, scalable manufacturing processes, and regulatory pathways, to provide a continued and long-term clinical benefit beyond current systemic therapies