In situ Endothelialization: Bioengineering Considerations to Translation

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.