In situ Endothelialization: Bioengineering Considerations to Translation

Abstract

Improving patency rates of current cardiovascular implants remains a major challenge. It is widely accepted that regeneration of a healthy endothelium layer on biomaterials could yield the perfect blood-contacting surface. Earlier efforts in pre-seeding endothelial cells in vitro demonstrated success in enhancing patency, but translation to the clinic is largely hampered due to its impracticality. In situ endothelialization, which aims to create biomaterial surfaces capable of self-endothelializing upon implantation, appears to be an extremely promising solution, particularly with the utilization of endothelial progenitor cells (EPCs). Nevertheless, controlling cell behavior in situ using immobilized biomolecules or physical patterning can be complex, thus warranting careful consideration. This review aims to provide valuable insight into the rationale and recent developments in biomaterial strategies to enhance in situ endothelialization. In particular, a discussion on the important bio-/nanoengineering considerations and lessons learnt from clinical trials are presented to aid the future translation of this exciting paradigm.

Hematologic concerns in extracorporeal membrane oxygenation

“…Endothelialization of circuitry can be accomplished via 2 techniques. The first is in vitro pre‐endothelialization of the circuit and the second is endothelial progenitor cells (EPCs) based on in vivo induced self‐endothelialization 57‐59 . In vitro endothelialization directly seeds autologous endothelial cells to form a monolayer along the internal surface of synthetic vascular grafts.…”

Electrospun PCL/keratin/AuNPs mats with the catalytic generation of nitric oxide for potential of vascular tissue engineering

“…Furthermore, the stability of the preseeded endothelial cell monolayer in vivo remains a significant concern. The latter strategy aims to promote regeneration of a functional endothelium directly on to blood‐contacting surfaces of vascular devices after implantation in vivo . In comparison, the in situ VTE strategy is more attractive by addressing the limitations of in vitro endothelialization.…”

“…The latter strategy aims to promote regeneration of a functional endothelium directly on to blood-contacting surfaces of vascular devices after implantation in vivo. [4][5][6][7] In comparison, the in situ VTE strategy is more attractive by addressing the limitations of in vitro endothelialization. For this approach, the scaffold plays a central role in replacing vascular functions immediately upon implantation, which would gradually degrade with the cells colonizing to form blood tissue.…”

Continuously Grooved Stent Struts for Enhanced Endothelial Cell Seeding

“…Biomaterials containing or attracting endothelial cells have been applied in various preclinical and clinical studies in an effort to reduce neointimal proliferation [10]. Examples of cell types used for in vitro studies include human umbilical vein endothelial cells (HUVECs), endothelial progenitor cells and genetically engineered cells [11–15].…”