Atorvastatin-Loaded Hydrogel Affects the Smooth Muscle Cells of Human Veins

Dubuis, Céline; May, Laurence; Alonso, Florian; Luca, Ludmila; Mylonaki, Ioanna; Meda, Paolo; Delié, Florence; Jordan, Olivier; Déglise, Sebastien; Corpataux, Jean-Marc; Saucy, François; Haefliger, Jacques‐Antoine

doi:10.1124/jpet.113.208769

Cited by 24 publications

(20 citation statements)

References 53 publications

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“…The cability of the ELR hydrogels to support cell proliferation is in agreement with previous studies in which human fibroblasts from the foreskin and human umbilical vein endothelial cells seeded on ELRs showed a population doubling time (PDT) of 34-48 h and 40-75 h respectively, as estimated from [8,43]. In the present study, we have estimated PDT of 72-96 h, which is in accordance with the proliferation rate reported in the literature for human vein SMCs [44] Additionally, the cells were not confined to the surface of the click-ELR scaffold, but they were able to infiltrate through the pores (Figure 6c), which provides evidence of the suitability of the pore size to support cell colonization. Moreover, the deposition of ECM was also patent (Figure 6d).…”

Section: Cell Ingrowth and Ecm Productionsupporting

confidence: 92%

Macroporous click-elastin-like hydrogels for tissue engineering applications

Fernández‐Colino

Wolf

Keijdener

et al. 2018

Materials Science and Engineering: C

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Elastin is a key extracellular matrix (ECM) protein that imparts functional elasticity to tissues and therefore an attractive candidate for bioengineering materials. Genetically engineered elastin-like recombinamers (ELRs) maintain inherent properties of the natural elastin (e.g. elastic behavior, bioactivity, low thrombogenicity, inverse temperature transition) while featuring precisely controlled composition, the possibility for biofunctionalization and non-animal origin. Recently the chemical modification of ELRs to enable their crosslinking via a catalyst-free click chemistry reaction, has further widened their applicability for tissue engineering. Despite these outstanding properties, the generation of macroporous click-ELR scaffolds with controlled, interconnected porosity has remained elusive so far. This significantly limits the potential of these materials as the porosity has a crucial role on cell infiltration, proliferation and ECM formation. In this study we propose a strategy to overcome this issue by adapting the salt leaching/gas foaming technique to click-ELRs. As result, macroporous hydrogels with tuned pore size and mechanical properties in the range of many native tissues were reproducibly obtained as demonstrated by rheological measurements and quantitative analysis of fluorescence, scanning electron and two-photon microscopy images. Additionally, the appropriate size and interconnectivity of the pores enabled smooth muscle cells to migrate into the click-ELR scaffolds and deposit extracellular matrix. The macroporous structure together with the elastic performance and bioactive character of ELRs, the specificity and non-toxic character of the catalyst-free click-chemistry reaction, make these scaffolds promising candidates for applications in tissue regeneration. This work expands the potential use of ELRs and click chemistry systems in general in different biomedical fields.

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Section: Cell Ingrowth and Ecm Productionsupporting

confidence: 92%

Macroporous click-elastin-like hydrogels for tissue engineering applications

Fernández‐Colino

Wolf

Keijdener

et al. 2018

Materials Science and Engineering: C

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“…The human smooth muscle cells were prepared from explants culture, as previously described [ 18 – 20 ]. Briefly, primary smooth muscle cells were cultured from human saphenous veins from a similar cohort used for ex-vivo perfusion.…”

Section: Methodsmentioning

confidence: 99%

Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia

et al. 2015

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Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microarray analysis of vein grafts in a model of bilateral rabbit jugular vein graft revealed Cx43 as an early upregulated gene. Additional experiments conducted using an ex-vivo human saphenous veins perfusion system (EVPS) confirmed that Cx43 was rapidly increased in human veins subjected ex-vivo to arterial hemodynamics. Cx43 knock-down by RNA interference, or adenoviral-mediated overexpression, respectively inhibited or stimulated the proliferation of primary human VSMC in vitro. Furthermore, Cx blockade with carbenoxolone or the specific Cx43 inhibitory peptide 43gap26 prevented the burst in myointimal proliferation and IH formation in human saphenous veins. Our data demonstrated that Cx43 controls proliferation and the formation of IH after arterial engraftment.

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“…Prepare the medium. Based on previous studies 5, [11][12][13][14] , choose RPMI-1640, supplemented with Glutamax, 12.5% fetal calf serum, and 1% antibiotic-antimycotic solution (10,000 U/ml penicillin G, plus 10 mg/ml streptomycin sulfate, plus 25 mg/ml amphotericin B, plus 0.5 μg/ ml: gentamycin). Shear stress (SS) is given by SS= 4 μQ/π*r 3 Q is the flow rate (ml/sec), r the radius (cm) of the vein segment, and μ is the viscosity of the perfusion medium.…”

Section: Evps Designmentioning

confidence: 99%

Procedure for Human Saphenous Veins <em>Ex Vivo</em> Perfusion and External Reinforcement

Longchamp

Allagnat²,

Bérard

et al. 2014

JoVE

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The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal hyperplasia (IH) that eventually leads to vessel occlusion and graft failure. Mechanical forces, particularly low shear stress and high wall tension, are thought to initiate and to sustain these cellular and molecular changes, but their exact contribution remains to be unraveled. To selectively evaluate the role of pressure and shear stress on the biology of IH, an ex vivo perfusion system (EVPS) was created to perfuse segments of human saphenous veins under arterial regimen (high shear stress and high pressure). Further technical innovations allowed the simultaneous perfusion of two segments from the same vein, one reinforced with an external mesh. Veins were harvested using a no-touch technique and immediately transferred to the laboratory for assembly in the EVPS. One segment of the freshly isolated vein was not perfused (control, day 0). The two others segments were perfused for up to 7 days, one being completely sheltered with a 4 mm (diameter) external mesh. The pressure, flow velocity, and pulse rate were continuously monitored and adjusted to mimic the hemodynamic conditions prevailing in the femoral artery. Upon completion of the perfusion, veins were dismounted and used for histological and molecular analysis. Under ex vivo conditions, high pressure perfusion (arterial, mean = 100 mm Hg) is sufficient to generate IH and remodeling of human veins. These alterations are reduced in the presence of an external polyester mesh.

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Atorvastatin-Loaded Hydrogel Affects the Smooth Muscle Cells of Human Veins

Cited by 24 publications

References 53 publications

Macroporous click-elastin-like hydrogels for tissue engineering applications

Macroporous click-elastin-like hydrogels for tissue engineering applications

Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia

Procedure for Human Saphenous Veins <em>Ex Vivo</em> Perfusion and External Reinforcement

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