Comparison of in Vascular Bioreactors and In Vivo Models of Degradation and Cellular Response of Mg-Zn-Mn Stents.

Traditional in vitro evaluation criteria of magnesium (Mg)-based stents cannot reflect the degradation process in vivo, due to the interdependence and interference between biodegradable properties and bioenvironment. The current direct and indirect evaluation approaches of in vitro biocompatibility do not have a hydrodynamic environment and vascular biological structure existing in vivo. Herein, we designed a vascular bioreactor to provide an ex vivo culture environment for vessels, which reveals the degradation behavior of Mg-Zn-Mn stent and the effect of its degradation on cells. We reported that rabbit carotid arteries could maintain native morphology and viability in the bioreactor under the best condition within a flow rate of 5.4 mL min-1 and a culture time of one week. With this culture condition, Mg-Zn-Mn stents were implanted into the arteries in the bioreactors and compared with in vivo rabbit models. The arteries maintained cell survival in the bioreactor, but the cell attachment was absent on the stent struts, associated with a fast degradation. Conversely, the stents achieved a rapid and complete endothelialization in vivo for two weeks. This study could provide a correlation and difference of the degradation behavior and cellular response to the degradation of Mg-based stent between ex vivo and in vivo approaches.

A tough nitric oxide-eluting hydrogel coating suppresses neointimal hyperplasia on vascular stent.

Vascular stent is viewed as one of the greatest advancements in interventional cardiology. However, current approved stents suffer from in-stent restenosis associated with neointimal hyperplasia or stent thrombosis. Herein, we develop a nitric oxide-eluting (NOE) hydrogel coating for vascular stents inspired by the biological functions of nitric oxide for cardiovascular system. Our NOE hydrogel is mechanically tough and could selectively facilitate the adhesion of endothelial cells. Besides, it is non-thrombotic and capable of inhibiting smooth muscle cells. Transcriptome analysis unravels the NOE hydrogel could modulate the inflammatory response and induce the relaxation of smooth muscle cells. In vivo study further demonstrates vascular stents coated with it promote rapid restoration of native endothelium, and persistently suppress inflammation and neointimal hyperplasia in both leporine and swine models. We expect such NOE hydrogel will open an avenue to the surface engineering of vascular implants for better clinical outcomes.