In vitro pre-endothelialisation of human cell-derived biomimetic regenerative matrices

Endothelial progenitor cell-based in vitro pre-endothelialisation of human cell-derived biomimetic regenerative matrices for next-generation transcatheter heart valve applications

The haemocompatibility of cardiovascular implants is a major clinical challenge. To date, optimal antithrombotic properties are lacking. Next-generation tissue-engineered heart valves (TEHVs) made from tissue-engineered extracellular matrices (hTEMs) of human cells demonstrated their re-cellularisation capacity in vivo and may be promising candidates to avoid antithrombotic therapy.

To further improve their haemocompatibility, we tested the potential of hTEMs before endothelialisation with human blood-derived endothelial colony-forming cells (ECFCs) and umbilical vein cells (control) cultured under static and dynamic orbital conditions with either FBS or hPL.

ECFC performance was assessed by scratch test, recapitulating surface damage occurring in transcatheter valves during crimping procedures. Our study demonstrated: feasibility to form confluent and functional endothelium on hTEMs with expression of endothelium-specific markers; ECFC migration and confluence restoration after crimp testing; hPL-induced formation of neo-microvessel-like structures; feasibility of preendothelialisation of hTEMs-based TEHVs and ECFCs remaining on their surface after crimping. Our findings may stimulate new directions towards next-generation preendothelialised implants with improved haemocompatibility, beneficial for selected high-risk patients.