Tissue engineering of a collagen-based vascular media

Schutte, Stacey C.; Chen, Zhenzhen; Brockbank, Kelvin G.M.; Nerem, Robert M.

doi:10.4161/org.6.4.12651

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…Indeed, the force generated by the tissue‐engineered vessels in response to contractile agonists was about 10 times below those observed for human veins and arteries (Plass et al , ). However, their contractile properties were similar or superior to other reconstructed vessels reported in the literature (Schutte et al , ).…”

Section: Discussionsupporting

confidence: 75%

Microstructured human fibroblast-derived extracellular matrix scaffold for vascular media fabrication

Bourget

Laterreur

Gauvin

et al. 2016

J Tissue Eng Regen Med

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In the clinical and pharmacological fields, there is a need for the production of tissue-engineered small-diameter blood vessels. We have demonstrated previously that the extracellular matrix (ECM) produced by fibroblasts can be used as a scaffold to support three-dimensional (3D) growth of another cell type. Thus, a resistant tissue-engineered vascular media can be produced when such scaffolds are used to culture smooth muscle cells (SMCs). The present study was designed to develop an anisotropic fibroblastic ECM sheet that could replicate the physiological architecture of blood vessels after being assembled into a small diameter vascular conduit. Anisotropic ECM scaffolds were produced using human dermal fibroblasts, grown on a microfabricated substrate with a specific topography, which led to cell alignment and unidirectional ECM assembly. Following their devitalization, the scaffolds were seeded with SMCs. These cells elongated and migrated in a single direction, following a specific angle relative to the direction of the aligned fibroblastic ECM. Their resultant ECM stained for collagen I and III and elastin, and the cells expressed SMC differentiation markers. Seven days after SMCs seeding, the sheets were rolled around a mandrel to form a tissue-engineered vascular media. The resulting anisotropic ECM and cell alignment induced an increase in the mechanical strength and vascular reactivity in the circumferential direction as compared to unaligned constructs. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Discussionsupporting

confidence: 75%

Microstructured human fibroblast-derived extracellular matrix scaffold for vascular media fabrication

Bourget

Laterreur

Gauvin

et al. 2016

J Tissue Eng Regen Med

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“…Prior work, as referenced in Table 1 , has evaluated endothelium-independent vasoconstriction of TEBVs in response to serotonin, endothelin-1, and prostaglandin 17 40 . The vasoconstriction of TEBVs produced with collagen gels embedded with rat smooth muscle cells has been evaluated destructively through changes in tension upon exposure to endothelin-1, bradykinin, phenylephrine, and sodium nitroprusside 41 . Recently, we evaluated endothelium-independent vasoconstriction in a TEBV after six weeks of fabrication using the cell sheet method 42 .…”

Section: Discussionmentioning

confidence: 99%

Human Vascular Microphysiological System for in vitro Drug Screening

Fernández

Yen

Perez

et al. 2016

Sci Rep

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In vitro human tissue engineered human blood vessels (TEBV) that exhibit vasoactivity can be used to test human toxicity of pharmaceutical drug candidates prior to pre-clinical animal studies. TEBVs with 400–800 μM diameters were made by embedding human neonatal dermal fibroblasts or human bone marrow-derived mesenchymal stem cells in dense collagen gel. TEBVs were mechanically strong enough to allow endothelialization and perfusion at physiological shear stresses within 3 hours after fabrication. After 1 week of perfusion, TEBVs exhibited endothelial release of nitric oxide, phenylephrine-induced vasoconstriction, and acetylcholine-induced vasodilation, all of which were maintained up to 5 weeks in culture. Vasodilation was blocked with the addition of the nitric oxide synthase inhibitor L-NG-Nitroarginine methyl ester (L-NAME). TEBVs elicited reversible activation to acute inflammatory stimulation by TNF-α which had a transient effect upon acetylcholine-induced relaxation, and exhibited dose-dependent vasodilation in response to caffeine and theophylline. Treatment of TEBVs with 1 μM lovastatin for three days prior to addition of Tumor necrosis factor – α (TNF-α) blocked the injury response and maintained vasodilation. These results indicate the potential to develop a rapidly-producible, endothelialized TEBV for microphysiological systems capable of producing physiological responses to both pharmaceutical and immunological stimuli.

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“…Histological imaging corroborates these findings (Figure 8, H&E staining with collagen in pale pink) – not much differences are observed in between t = 0 day and t = 1 day, however, sections of the conduits at t = 7 days show striking differences with some inflammatory reaction in the lumen side developing. Void spaces are present in between scaffold fibers and forming tissue, however much less void space is present in the later time point as substantial amount of tissue compaction, ECM production and cross-linking, and mechanical functionalization of the de novo tissue is known to occur [4, 56]. …”

Section: Discussionmentioning

confidence: 99%

A mathematical model for the determination of forming tissue moduli in needled-nonwoven scaffolds

2017

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Formation of engineering tissues (ET) remains an important scientific area of investigation for both clinical translational and mechanobiological studies. Needled-nonwoven (NNW) scaffolds represent one of the most ubiquitous biomaterials based on their well-documented capacity to sustain tissue formation and the unique property of substantial construct stiffness amplification, the latter allowing for very sensitive determination of forming tissue modulus. Yet, their use in more fundamental studies is hampered by the lack of (1) substantial understanding of the mechanics of the NNW scaffold itself under finite deformations and means to model the complex mechanical interactions between scaffold fibers, cells, and de novo tissue; and (2) rational models with reliable predictive capabilities describing their evolving mechanical properties and their response to mechanical stimulation. Our objective is to quantify the mechanical properties of the forming ET phase in constructs that utilize NNW scaffolds. We present herein a novel mathematical model to quantify their stiffness based on explicit considerations of the modulation of NNW scaffold fiber-fiber interactions and effective fiber stiffness by surrounding de novo ECM. Specifically, fibers in NNW scaffolds are effectively stiffer than if acting alone due to extensive fiber-fiber cross-over points that impart changes in fiber geometry, particularly crimp wavelength and amplitude. Fiber-fiber interactions in NNW scaffolds also play significant role in the bulk anisotropy of the material, mainly due to fiber buckling and large translational out-of-plane displacements occurring to fibers undergoing contraction. To calibrate the model parameters, we mechanically tested impregnated NNW scaffolds with polyacrylamide (PAM) gels with a wide range of moduli with values chosen to mimic the effects of surrounding tissues on the scaffold fiber network. Results indicated a high degree of model fidelity over a wide range of planar strains. Lastly, we illustrated the impact of our modeling approach quantifying the stiffness of engineered ECM after in vitro incubation and early stages of in vivo implantation obtained in a concurrent study of engineered tissue pulmonary valves in an ovine model.

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Tissue engineering of a collagen-based vascular media

Cited by 8 publications

References 34 publications

Microstructured human fibroblast-derived extracellular matrix scaffold for vascular media fabrication

Microstructured human fibroblast-derived extracellular matrix scaffold for vascular media fabrication

Human Vascular Microphysiological System for in vitro Drug Screening

A mathematical model for the determination of forming tissue moduli in needled-nonwoven scaffolds

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