Approach for Fabricating Tissue Engineered Vascular Grafts with Stable Endothelialization

Jimenez-Vergara, Andrea Carolina; Guiza-Arguello, Viviana; Becerra-Bayona, Silvia; Muñoz-Pinto, Dany J.; McMahon, Rebecca E.; Morales, Anabel; Cubero-Ponce, Lynnette; Hahn, Mariah S.

doi:10.1007/s10439-010-0049-8

Cited by 16 publications

(13 citation statements)

References 36 publications

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“…To evaluate HAEC phenotype at confluence, we focused our attention on five common EC markers: VE-cadherin, PECAM-1, NOS3, TM, and E-selectin. 40 The expression of VE-cadherin, PECAM-1, NOS3 and TM are, in general, positively correlated with a quiescent EC phenotype, while E-selectin is negatively correlated with quiescence. The expression of PECAM-1 and VE-cadherin were not significantly different on the 8 mg/mL and 12 mg/mL PEG-Scl2-2 hydrogels relative to the PEG-collagen controls at either the gene or the protein level.…”

Section: Discussionmentioning

confidence: 97%

Collagen-mimetic hydrogels promote human endothelial cell adhesion, migration and phenotypic maturation

et al. 2015

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This work evaluates the response of human aortic endothelial cells (HAECs) to thromboresistant collagen-mimetic hydrogel coatings toward improving the biocompatibility of existing “off-the-shelf” small-caliber vascular grafts. Specifically, bioactive hydrogels – previously shown to support α1/α2 integrin-mediated cell adhesion but to resist platelet activation – were fabricated by combining poly(ethylene glycol) (PEG) with a 120 kDa, triple-helical collagen-mimetic protein(Scl2-2) containing the GFPGER adhesion sequence. Analysis of HAECs seeded onto the resulting PEG-Scl2-2 hydrogels demonstrated that HAEC adhesion increased with increasing Scl2-2 concentration, while HAEC migration rate decreased over this same concentration range. In addition, evaluation of HAEC phenotype at confluence indicated significant differences in the gene expression of NOS3, thrombomodulin, and E-selectin on the PEG-Scl2-2 hydrogels relative to PEG-collagen controls. At the protein level, however, only NOS3 was significantly different between the PEG-Scl2-2 and PEG-collagen surfaces. Furthermore, PECAM-1 and VE-cadherin expression on PEG-Scl2-2 hydrogels versus PEG-collagen controls could not be distinguished at either the gene or protein level. Cumulatively, these data indicate the PEG-Scl2-2 hydrogels warrant further investigation as “off-the-shelf” graft coatings. In future studies, the Scl2-2 protein can potentially be modified to include additional extracellular matrix or cytokine binding sites to further improve endothelial cell responses.

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Section: Discussionmentioning

confidence: 97%

Collagen-mimetic hydrogels promote human endothelial cell adhesion, migration and phenotypic maturation

et al. 2015

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“…19 Seeding of representative cell populations-both endothelial cells (ECs) and smooth muscle cells (SMCs)-should modulate the thrombogenicity of the endothelial layer by covering the synthetic luminal surface with adherent endothelial cells. 12,20 Signaling between these cell populations plays a significant role in blood vessel function. At the interface between blood and the vessel wall, ECs are directly exposed to blood flow-induced shear stress.…”

Section: Discussionmentioning

confidence: 99%

Vascular Wall Engineering Via Femtosecond Laser Ablation: Scaffolds with Self-Containing Smooth Muscle Cell Populations

et al. 2011

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For tissue-engineered vascular grafts to reach their full potential, three-dimensional (3D) cellular micro-integration will be necessary. In this study, we utilize femtosecond laser ablation to produce microchannels inside electrospun polycaprolactone (PCL) scaffolds. These microchannels potentially provide spatially controlled cell distributions approaching those observed in vivo. The ability of such laser-ablated microchannels to direct cell seeding was evaluated. The dimensions chosen were 100 μm wide, 100 μm deep and 10 mm long. Femtosecond laser ablation successfully produced these microchannels in the scaffolds without substantially altering the ~900 nm diameter fibers. Flow within these microchannels was studied by injecting fluorescent polystyrene bead solutions. Direct measurement of bead motion yielded an inlet velocity of 2.78 cm s(-1). This was used for modeling two-dimensional (2D) flow using computational fluid dynamics to estimate flow profiles within the microchannel. Successful demonstrations of bead flow were followed by seeding of 500,000 human coronary artery smooth muscle cells (HCASMCs) in proliferative medium at a rate of ~500 μL min(-1). Confocal microscopy and scanning electron microscopy confirmed that the HCASMCs were seeded down the full 10-mm length of the microchannel and stayed within its boundaries. Both nuclei and F-actin were observed within the seeded cells. The presence of F-actin filaments shows that the cells were adhered strongly to the scaffold and remained viable throughout the culture. The concept of "vascular wall engineering" producing intricate cell seeding through microchannels produced via femtosecond laser ablation was validated.

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“…For each of the cell studies below, MSCs were harvested at passage 4 and encapsulated at 7.5×10 5 cells/ml as described above. Collagen-PEGDA IPNs containing 3 mg/mL collagen and 6.0 kDa PEGDA were selected for evaluation due to the prior use of 10 % w/v 6.0 kDa PEGDA hydrogels in vascular tissue engineering studies [45, 46]. Cells were allowed to spread in the collagen network for 0 h, 4 h or 6 h in either SFM or CM prior to infiltration with an 11.7% w/v 6.0 kDa PEGDA solution for 60 min, followed by 6 min exposure to longwave UV light.…”

Section: Methodsmentioning

confidence: 99%

Characterization of sequential collagen-poly(ethylene glycol) diacrylate interpenetrating networks and initial assessment of their potential for vascular tissue engineering

et al. 2015

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Collagen hydrogels have been widely investigated as scaffolds for vascular tissue engineering due in part to the capacity of collagen to promote robust cell adhesion and elongation. However, collagen hydrogels display relatively low stiffness and strength, are thrombogenic, and are highly susceptible to cell-mediated contraction. In the current work, we develop and characterize a sequentially-formed interpenetrating network (IPN) that retains the benefits of collagen, but which displays enhanced mechanical stiffness and strength, improved thromboresistance, high physical stability and resistance to contraction. In this strategy, we first form a collagen hydrogel, infuse this hydrogel with poly(ethylene glycol) diacrylate (PEGDA), and subsequently crosslink the PEGDA by exposure to longwave UV light. These collagen-PEGDA IPNs allow for cell encapsulation during the fabrication process with greater than 90% cell viability via inclusion of cells within the collagen hydrogel precursor solution. Furthermore, the degree of cell spreading within the IPNs can be tuned from rounded to fully elongated by varying the time delay between the formation of the cell-laden collagen hydrogel and the formation of the PEGDA network. We also demonstrate that these collagen-PEGDA IPNs are able to support the initial stages of smooth muscle cell lineage progression by elongated human mesenchymal stems cells.

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Approach for Fabricating Tissue Engineered Vascular Grafts with Stable Endothelialization

Cited by 16 publications

References 36 publications

Collagen-mimetic hydrogels promote human endothelial cell adhesion, migration and phenotypic maturation

Collagen-mimetic hydrogels promote human endothelial cell adhesion, migration and phenotypic maturation

Vascular Wall Engineering Via Femtosecond Laser Ablation: Scaffolds with Self-Containing Smooth Muscle Cell Populations

Characterization of sequential collagen-poly(ethylene glycol) diacrylate interpenetrating networks and initial assessment of their potential for vascular tissue engineering

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