Investigation Of Heparin-PLL Nanoparticles Loaded VEGF/SDF-1? For Directional Induced-Endothelialization

As one of the most cardiovascular disease,coronary heart disease is seriously threat to human health.There are drug therapy,coronary artery bypass surgery and Percutaneous coronary intervention for the treatment in cardiovascular disease.Percutaneous coronary intervention has become an important therapy in Cardiovascular disease(CVD).Although the metal stents have solved many clinical problems,the lack biocompatibility of stent metal as well as vascular endothelium injury caused by stent implantation and restenosis remain problem.Multifunctional biomimetic layer is one of the most important ways to realize endothelialization and ultimately solve the above problems.Hydrogels are structurally similar to the tissue extracellular matrix(ECM);they can be processed under relatively mild conditions and can be delivered in a minimally invasive manner.Moreover,hydrogels can be designed to degrade in a timely fashion that coincides with the angiogenic process.In this study,Several bio-functional HA-PAD hydrogel made of dopamine and hyaluronic acid in different ratios were fabricated.The optimal HA-DAP hydrogel was elected out by a series of material characterization and cell compatibility evaluation.Then,Hep/PLL nanoparticles loading VEGF were added to HA-DAP Hydrogels,which exploreed the effect of this system on endothelial cells.Dopamine reacted with hyaluronic acid under acidic conditions.Then,the Hep/PLL nanoparticles loading with VEGF were added to the HA-Catechol Derivative solution.Finally,a gel formed by adding a certain amount of sodium periodate.The cohesive mechanism is that the deprotonation of the hydroxyl groups in catechol results in quinone formation,resulting in cohesive crosslinking reactions.The catechol was determined by ultraviolet-visible(UVVis)spectroscopy at 280 nm using HA-Catechol Derivative solutions,The cross-sectional morphology of HA-DAP hydrogel was observed by scanning electron microscopy(SEM),The swelling ratio of the hydrogel decreased with increaseing the concentration of dopamine,the endothelial cell compatibility results show that HA-DAP3 had better cell compatibility(endothelial cell adhesion,endothelial cells cultured for 1 day,3 days in number,morphology and activity)than other samples.The different amounts of heparin/polylysine nanoparticles were added into the hydrogel.The nanoparticles on the gel surface were observed by scanning electron microscopy(SEM).Nanoparticles had gathered in the hydrogel,With the increase of nanoparticles concentration,the gather were more serious.Endothelial cell compatibility results showed that HA-DAP3-NP10(dopamine reaction concentration 3mg/mL,lOuL nanoparticles was added to lOOuL gel solution)had better cell compatibility(endothelial cell adhesion,endothelial cells cultured for 1 day,3 days in number,morphology and activity)than other samples.The Hep/PLL nanoparticles loading with VEGF were added to HA-DAP3 hydrogel(HA-DAP3-NP10V).The release profile of VEGF was tested by elisa kit,HA-DAPS-NP10V was found to have a slow release of VEGF,but the effect was not significant.Samples loading VEGF showed better cell compatibility(endothelial cell proliferation,endothelial cell spread and endothelial cell migration).HA-DAP3-NP10V and HA-DAP3-V(VEGF was directly added to HA-DAP3 hydrogel)did not differ significantly in promoting endothelial cell proliferation and endothelial cell migration.In conclusion,In this study,we successfully constructed the system of HA-DAP3 hydrogel packageing Hep/PLL-VEGF nanoparticles,and which compared with the direct addition of VEGF to HA-DAP3 hydrogel.HA-DAP3-NP10V was found to have a slow release of VEGF,but the effect was not significant.HA-DAP3-NP10V and HA-DAP3-V did not differ significantly in promoting endothelial cell proliferation and endothelial cell migration.