A tailored extracellular matrix (ECM)-Mimetic coating for cardiovascular stents by stepwise assembly of hyaluronic acid and recombinant human type III collagen

Collagen, a central component of the extracellular matrix (ECM), has been widely applied in tissue engineering, among others, for wound healing or bone and nerve regeneration. However, the inherent thrombogenic properties of collagen hinder the application in blood-contacting devices. Herein, a brand-new recombinant human type III collagen (hCOLIII) was explored that does not present binding sites for platelets while retaining the affinity for endothelial cells. The hCOLIII together with hyaluronic acid (HA) were deposited on the substrates via layer-by-layer assembly to form an ECM-mimetic multilayer coating. In vitro platelet adhesion and ex vivo blood circulation tests demonstrated prominent thromboprotective properties for the hCOLIII-based ECMmimetic coating. In addition, the coating effectively guided the vascular cell fate by supporting the proliferation of endothelial cells and inhibiting the proliferation of smooth muscle cells by differentiating them to a more contractile phenotype. A polylactic acid (PLA) stent coated with hCOLIII-based ECM-mimetic coating was implanted in the abdominal aorta of rabbits to investigate the healing of the neointima. The enhanced endothelialization, suppressed inflammatory response, inhibition of excessive neointimal hyperplasia, and the superior thromboprotection strongly indicated the prospect of the hCOLIII-based ECM-mimetic coating as a tailored blood-contacting material for cardiovascular stents.

Automated summary

A new recombinant human type III collagen (hCOLIII) without platelet binding sites but with affinity for endothelial cells was explored, together with hyaluronic acid (HA), to form an ECM-mimetic multilayer coating. The coating demonstrated significant thromboprotective properties and guided vascular cell fate by supporting endothelial cell proliferation and inhibiting smooth muscle cell proliferation. Implantation of a polylactic acid (PLA) stent coated with hCOLIII in rabbit abdominal aorta showed enhanced endothelialization, suppressed inflammatory response, inhibition of neointimal hyperplasia, and superior thromboprotection, indicating the potential of hCOLIII-based ECM-mimetic coating as a tailored blood-contacting material for cardiovascular stents.