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Abstract: Restenosis, thrombosis formation and delayed endothelium regeneration continue to be problematic for coronary artery stent therapy. To improve the hemocompatibility of the cardiovascular implants and selectively direct vascular cell behavior, a novel kind of heparin/poly-l-lysine (Hep/PLL) nanoparticle was developed and immobilized on a dopamine-coated surface. The stability and structural characteristics of the nanoparticles changed with the Hep:PLL concentration ratio. A Hep density gradient was created on a surface by immobilizing nanoparticles with various Hep:PLL ratios on a dopamine-coated surface. Antithrombin III binding quantity was significantly enhanced, and in plasma the APTT and TT times as coagulation tests were prolonged, depending on the Hep density. A low Hep density is sufficient to prevent platelet adhesion and activation. The sensitivity of vascular cells to the Hep density is very different: high Hep density inhibits the growth of all vascular cells, while low Hep density could selectively inhibit smooth muscle cell hyperplasia but promote endothelial progenitor cells and endothelial cell proliferation. These observations provide important guidance for modification of surface heparinization. We suggest that this method will provide a potential means to construct a suitable platform on a stent surface for selective direction of vascular cell behavior with low side effects. [Copyright &y& Elsevier]

Graphical abstract The adhering and spreading of endothelia cells (ECs) and macrophages (MAs) to SEMA4D/Heparin modified surface. Highlights • Monitoring the EC/MA interactions with biomaterials under dynamic circumstances. • Surfaces with high heparin promoted EC adhesion and spreading. • Surfaces with high SEMA4D enhanced both MA adhesion and spreading. • Specific igand-receptor interactions promote adhesion and spreading for either EC or MA. Abstract In vitro evaluation techniques that address cellular interactions under dynamic circumstances are required for the development of advanced biomaterials. In this study, quartz crystal microbalance and dissipation (QCM-D) provided a surface sensitive technique that enabled real-time monitoring of the adhesion and spreading response of endothelial cells (ECs) and macrophages (MAs) to soluble-semaphoring 4D (SEMA4D)/heparin modified substratum. The high heparin and low SEMA4D of substratum promoted ECs adhering and spreading. However, surfaces with high SEMA4D and low heparin enhanced MA adhering and spreading. Furthermore, DF plots of QCM-D indicated that the adhering and spreading of MAs were mainly mediated via the ligand-receptor interaction of SEMA4D-CD72, while both adhering and spreading of ECs were mainly mediated via heparin-induced integrin binding. This study suggests that QCM-D combined with other appropriate methods can be utilized to explore the mechanisms for cellular interaction with biomaterial surfaces. [ABSTRACT FROM AUTHOR]

Surface biofunctional modification of coronary artery stent to improve the hemocompatibility and selectively accelerate endothelium regeneration but prevent restenosis have been become a new hotspot. For this, a novel method was developed in this work by co-immobilization of Ln and heparin complex on poly- l -lysine modified Ti surface. Take the advantage of the specific interaction between Ln and heparin, Ln and heparin complexes with different concentration ratios were set up for creating different exposure density of these two types of biomolecules. According to biocompatibility evaluation results, the Hep/Ln complexes modified surface displayed less platelet adhesion and activation. Especially, on L(150)H and L(200)H surface, the AT III binding quantity, APTT value and anti-coagulation property of modified surface were significantly promoted. Furthermore, the adherent density and proliferation activity of ECs and EPCs were positively correlated with Ln concentration. Notably, the proliferation of both ECs and EPCs on L(100)H, L(150)H and L(200)H surface were greatly promoted. Another hand, the proliferation activity of SMCs was significantly inhibited on Hep/Ln modified surfaces, which was considered mainly due to the inhibitory effect of heparin to SMCs. According to the existing results, this study demonstrated that in a certain range of heparin and laminin concentration ratio, the biological behavior of platelets, ECs, EPCs and SMCs could be selectively directed. We suggested that this article provided a potential method to construct an adequate platform on a stent surface for accelerate endothelialization with low side effects. [ABSTRACT FROM AUTHOR]