Fabrication of a mimetic vascular graft using melt spinning with tailorable fiber parameters

Kampen, Kenny A. van; Fernández‐Pérez, Julia; Baker, Matthew B.; Mota, Carlos; Moroni, Lorenzo

doi:10.1016/j.bioadv.2022.212972

Cited by 9 publications

(17 citation statements)

References 58 publications

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“…Numerous studies have explored methods for inducing the circumferential alignment of SMCs in vitro. , Many of these studies rely on seeding SMC on surfaces with circumferentially aligned microgrooves that guide cellular alignment. , Nevertheless, these techniques are often slow, and developing 3D layers of circumferentially aligned cells remains difficult. Using mesenchymal stromal cells and circumferentially aligned fibers, researchers achieved alignment of smooth muscle cell-like layers along the microgrooves .…”

Section: Resultsmentioning

confidence: 99%

Spontaneous Orthogonal Alignment of Smooth Muscle Cells and Endothelial Cells Captures Native Blood Vessel Morphology in Tissue-Engineered Vascular Grafts

Alkazemi,

Huang,

Mail

et al. 2023

ACS Appl. Mater. Interfaces

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Tissue-engineered vascular grafts (TEVGs) have emerged as a potential alternative to autologous grafts for replacing small-diameter blood vessels during bypass surgery. The axial alignment of endothelial cells (ECs) and the circumferential alignment of smooth muscle cells (SMCs) are crucial for functional native blood vessels (NBVs). However, achieving this cellular alignment in TEVGs remains a formidable challenge. In this study, TEVGs were developed using a low-cost technique that aligned ECs axially and SMCs circumferentially within hours. The TEVGs comprised an electrospun polycaprolactone (PCL) layer and a gelatin methacryloyl (GelMA) cast layer. A freezing-induced alignment technique was developed that partially aligns the electrospun fibers axially, thereby promoting rapid axial alignment of ECs. Furthermore, SMCs cultured in a GelMA layer with intermediate stiffness (5−12 kPa) surrounding a PCL tube could promote conformation of the SMCs to the curvature of the PCL tube, resulting in their spontaneous circumferential alignment. Additionally, the TEVGs demonstrated mechanical properties similar to those of NBVs, which could facilitate future translation. This approach represents a significant advance in tissue engineering, enabling the fabrication of TEVGs with appropriate mechanical properties that recapitulate key NBV cell structural features within hours using a scalable and accessible method.

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Section: Resultsmentioning

confidence: 99%

Spontaneous Orthogonal Alignment of Smooth Muscle Cells and Endothelial Cells Captures Native Blood Vessel Morphology in Tissue-Engineered Vascular Grafts

Alkazemi,

Huang,

Mail

et al. 2023

ACS Appl. Mater. Interfaces

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“…The fiber diameter was 31.6 ± 3.9 μm, and it was not affected by the printhead speed. Fiber diameter can also be modified by changing the rotational speed of the collector, as demonstrated in an earlier work . In this study, this parameter was kept constant at 1060 rpm.…”

Section: Resultsmentioning

confidence: 99%

“…Melt spinning, the technique used in this and our previous study, is simple, requires low “technological” equipment, is versatile in the diameter of the tubes produced, and possesses the ability to control fiber alignment in the circumferential axis. Despite its many benefits, it is not a widespread technique for the fabrication of tubular scaffolds. , In a recent publication, Zhi and colleagues described the fabrication of scaffolds in a similar fashion to the one described here .…”

Section: Discussionmentioning

confidence: 99%

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Flexible, Suturable, and Leak-free Scaffolds for Vascular Tissue Engineering Using Melt Spinning

Fernández‐Pérez

Kampen

Mota

et al. 2023

ACS Biomater. Sci. Eng.

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Coronary artery disease affects millions worldwide. Bypass surgery remains the gold standard; however, autologous tissue is not always available. Hence, the need for an off-the-shelf graft to treat these patients remains extremely high. Using melt spinning, we describe here the fabrication of tubular scaffolds composed of microfibers aligned in the circumferential orientation mimicking the organized extracellular matrix in the tunica media of arteries. By variation of the translational extruder speed, the angle between fibers ranged from 0 to ∼30°. Scaffolds with the highest angle showed the best performance in a three-point bending test. These constructs could be bent up to 160% strain without kinking or breakage. Furthermore, when liquid was passed through the scaffolds, no leakage was observed. Suturing of native arteries was successful. Mesenchymal stromal cells were seeded on the scaffolds and differentiated into vascular smooth muscle-like cells (vSMCs) by reduction of serum and addition of transforming growth factor beta 1 and ascorbic acid. The scaffolds with a higher angle between fibers showed increased expression of vSMC markers alpha smooth muscle actin, calponin, and smooth muscle protein 22-alpha, whereas a decrease in collagen 1 expression was observed, indicating a positive contractile phenotype. Endothelial cells were seeded on the repopulated scaffolds and formed a tightly packed monolayer on the luminal side. Our study shows a one-step fabrication for ECM-mimicking scaffolds with good handleability, leakfree property, and suturability; the excellent biocompatibility allowed the growth of a bilayered construct. Future work will explore the possibility of using these scaffolds as vascular conduits in in vivo settings.

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“…To determine the stiffness of the EHM ring, mechanical analysis was performed using an Electroforce-3200 Series III multiaxial tensile tester (TA Instruments, Asse, Belgium) combined with a 1000 gf (10 N) load cell (1 kg/cm 2 ), as previously described [ 36 , 37 ]. Test setups and data acquisition were directed through the WinTest 7 operational software (TA Instruments).…”

Section: Methodsmentioning

confidence: 99%

Culturing of Cardiac Fibroblasts in Engineered Heart Matrix Reduces Myofibroblast Differentiation but Maintains Their Response to Cyclic Stretch and Transforming Growth Factor β1

et al. 2022

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Isolation and culturing of cardiac fibroblasts (CF) induces rapid differentiation toward a myofibroblast phenotype, which is partly mediated by the high substrate stiffness of the culture plates. In the present study, a 3D model of Engineered Heart Matrix (EHM) of physiological stiffness (Youngs modulus ~15 kPa) was developed using primary adult rat CF and a natural hydrogel collagen type 1 matrix. CF were equally distributed, viable and quiescent for at least 13 days in EHM and the baseline gene expression of myofibroblast-markers alfa-smooth muscle actin (Acta2), and connective tissue growth factor (Ctgf) was significantly lower, compared to CF cultured in 2D monolayers. CF baseline gene expression of transforming growth factor-beta1 (Tgfβ1) and brain natriuretic peptide (Nppb) was higher in EHM-fibers compared to the monolayers. EHM stimulation by 10% cyclic stretch (1 Hz) increased the gene expression of Nppb (3.0-fold), Ctgf (2.1-fold) and Tgfβ1 (2.3-fold) after 24 h. Stimulation of EHM with TGFβ1 (1 ng/mL, 24 h) induced Tgfβ1 (1.6-fold) and Ctgf (1.6-fold). In conclusion, culturing CF in EHM of physiological stiffness reduced myofibroblast marker gene expression, while the CF response to stretch or TGFβ1 was maintained, indicating that our novel EHM structure provides a good physiological model to study CF function and myofibroblast differentiation.

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Fabrication of a mimetic vascular graft using melt spinning with tailorable fiber parameters

Cited by 9 publications

References 58 publications

Spontaneous Orthogonal Alignment of Smooth Muscle Cells and Endothelial Cells Captures Native Blood Vessel Morphology in Tissue-Engineered Vascular Grafts

Spontaneous Orthogonal Alignment of Smooth Muscle Cells and Endothelial Cells Captures Native Blood Vessel Morphology in Tissue-Engineered Vascular Grafts

Flexible, Suturable, and Leak-free Scaffolds for Vascular Tissue Engineering Using Melt Spinning

Culturing of Cardiac Fibroblasts in Engineered Heart Matrix Reduces Myofibroblast Differentiation but Maintains Their Response to Cyclic Stretch and Transforming Growth Factor β1

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