In-stent restenosis and subsequent thrombosis remain a significant complication following the implantation of coronary stents. Different approaches have been used in developing novel coronary stents to protect against thrombosis and minimize restenosis. In the present study, we designed a biomacromolecular layer-by-layer coating with heparin, vascular endothelial growth factor (VEGF), and fibronectin onto nickel-free titanium surface to improve blood compatibility and endothelial cell proliferation. The multilayer assembling process was monitored by water contact angle and surface plasmon resonance, respectively. With increasing the number of layers, the deposition of polyelectrolyte as self-assembled ultrathin multilayer films showed linear growth of absorbance. In vitro blood compatibility results revealed that the fabricated layers prolonged activated partial thrombin time and prothrombin time, reduced platelets activation and aggregation, and reduced blood hemolysis rate. Cell adhesion and growth results showed that the assembled multilayer films significantly promoted cell attachment and growth, and the endothelialization property of the multilayer films was preferable compared with the untreated titanium disk. In conclusion, these results suggest that titanium surface modification using biofunctional multilayer films composed of heparin, VEGF, and fibronectin may serve as a potential approach to inhibit thrombosis and promote re-endothelialization of cardiovascular stents.
For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood–brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.
Atherosclerosis (AS) commonly occurs in the regions of the arterial tree with haemodynamic peculiarities, including local flow field disturbances, and formation of swirling flow and vortices. The aim of our study was to confirm low-density lipoprotein (LDL) concentration polarization in the vascular system in vitro and in vivo, and investigate the effects of LDL concentration polarization and flow field alterations on atherosclerotic localization. Red fluorescent LDL was injected into optically transparent Flk1: GFP zebrafish embryos, and the LDL distribution in the vascular lumen was investigated in vivo using laser scanning confocal microscopy. LDL concentration at the vascular luminal surface was found to be higher than that in the bulk. The flow field conditions in blood vessel segments were simulated and measured, and obvious flow field disturbances were found in the regions of vascular geometry change. The LDL concentration at the luminal surface of bifurcation was significantly higher than that in the straight segment, possibly owing to the atherogenic effect of disturbed flow. Additionally, a stenosis model of rabbit carotid arteries was generated. Atherosclerotic plaques were found to have occurred in the stenosis group and were more severe in the stenosis group on a high-fat diet. Our findings provide the first ever definite proof that LDL concentration polarization occurs in the vascular system in vivo. Both lipoprotein concentration polarization and flow field changes are involved in the infiltration/accumulation of atherogenic lipids within the location of arterial luminal surface and promote the development of AS.
We have demonstrated that blood flow is essential for vascular network formation, specifically for CVP angiogenesis in zebrafish. A novel genetic and mechanical mechanism was discovered in which ERK5 facilitates the integration of blood flow with the downstream klf2a-nos2b signaling for CVP angiogenesis.
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