Prosthetic vascular grafts engineered to combat calcification: Progress and future directions

Abstract

Calcification in prosthetic vascular conduits is a major challenge in cardiac and vascular surgery that compromises the long‐term performance of these devices. Significant research efforts have been made to understand the etiology of calcification in the cardiovascular system and to combat calcification in various cardiovascular devices. Novel biomaterial design and tissue engineering strategies have shown promise in preventing or delaying calcification in prosthetic vascular grafts. In this review, we highlight recent advancements in the development of acellular prosthetic vascular grafts with preclinical success in attenuating calcification through advanced biomaterial design. We also discuss the mechanisms of action involved in the designs that will contribute to the further understanding of cardiovascular calcification. Lastly, recent insights into the etiology of vascular calcification will guide the design of future prosthetic vascular grafts with greater potential for translational success.

Incorporation of Controlled Release Systems Improves the Functionality of Biodegradable 3D Printed Cardiovascular Implants

“…Therefore, the incorporation of anti-inflammatory agents offers a perspective to reduce inflammation and prevent calcification in the new generation of 3D printed biodegradable vascular grafts. 104 This strategy has been investigated using rapamycinloaded vascular grafts fabricated out of PCL and PGS. The drug-loaded graft demonstrated a positive effect on the phenotype of macrophages having switched to the M2 phenotype (lower Alizarin red staining) when compared to control grafts without rapamycin, resulting in anticalcification properties of the rapamycin-loaded vascular graft.…”

“…Designing vascular grafts with immunomodulatory capability modulating macrophages to an anti-inflammatory and antiosteogenic M2 phenotype can be a key strategy to attenuate the inflammation-associated calcification. Therefore, the incorporation of anti-inflammatory agents offers a perspective to reduce inflammation and prevent calcification in the new generation of 3D printed biodegradable vascular grafts . This strategy has been investigated using rapamycin-loaded vascular grafts fabricated out of PCL and PGS.…”

Advancements in Surface Modification Strategies of Blood-contacting Biomaterials to Improve Biocompatibility and Tissue Integration

“…Aside from thrombosis, fibrosis and calcification are other long term complications of synthetic vascular grafts. 19…”

“…16 Characterized by ectopic mineral formation in the form of calcium phosphate or other calcium salts (Figure 1f), calcification can increase the risk of heart attack, stroke, and limb amputation by contributing to vascular occlusion and through embolization of calcific deposits. 19 Additionally, vascular mineralization results in mechanical dysfunction of implants. Although recent research suggests that calcification is an active cellmediated process, the details of its pathogenesis remain uncertain.…”

“…Factors related to this phenomenon include matrix remodeling, endoplasmic reticulum stress, apoptosis, inflammation, and the generation of reactive oxygen species (ROS). 17,19 Because of the high prevalence of interstitial calcification, vascular graft materials that are resistant to calcification are urgently needed.…”