TY - JOUR
T1 - Vascular Grafts with Tailored Stiffness and a Ligand Environment via Multiarmed Polymer Sheath for Expeditious Regeneration
AU - Iglesias-Echevarria, Monica
AU - Johnson, Richard
AU - Rafuse, Michael
AU - Ding, Yonghui
AU - Tan, Wei
N1 - Funding Information:
The work was financially supported by National Heart, Lung, and Blood Institute R01HL119371 (W.T.).
Publisher Copyright:
©
PY - 2021/1/18
Y1 - 2021/1/18
N2 - The bypass graft is the mainstream of surgical intervention to treat vascular diseases. Ideal bypass materials, yet to be developed, require mechanical properties, availability, clinically feasible manufacturing logistics, and bioactivities with precise physicochemical cues defined to guide cell activities for arterial regeneration. Such needs instigated our fabrication of vascular grafts, which consist of coaxial, nanostructured fibers exhibiting a polycaprolactone (PCL) core and a photoclickable, 4-arm thiolated polyethylene glycol-norbornene (PEG-NB) sheath. The graft strength and bioactivity were modulated by the PCL concentration and the peptides (RGD, transforming growth factor β-1 or TGF-β1) conjugated to thiol-ene of PEG-NB, respectively. Structural, physical, and mechanical characterizations demonstrated that the fibrous grafts mimicked the key features of the native extracellular matrix, including a crosslinked fiber network for structural stability, viscoelasticity emulating arteries, hydration property, and high porosity for cell infiltration. Meanwhile, these grafts displayed strength and toughness exceeding or meeting surgical criteria. Furthermore, the grafts with higher PCL concentration (3 vs 1.8%) showed thicker fibers, lower porosity and pore size, and increased elastic and storage moduli. Graft bioactivity was determined by the mesenchymal stem cell (MSC) behaviors on the grafts and arterial regeneration in vivo using interposition grafting. Results showed that the cell adhesion and proliferation increased with the RGD density (25 vs 5 mM). After 1 week implantation, all peptide-functionalized PCL/PEG-NB grafts with or without MSC preseeding, as opposed to PCL grafts, showed expeditious endothelial lining, abundant vascular cell infiltration, and matrix production. Compared to RGD grafts, RGD/TGF-β1 grafts enhanced MSC differentiation into smooth muscle cells in vitro and developed thicker smooth muscle cell layers in vivo. Overall, the versatile porous vascular grafts offer superior properties and tunability for future translation.
AB - The bypass graft is the mainstream of surgical intervention to treat vascular diseases. Ideal bypass materials, yet to be developed, require mechanical properties, availability, clinically feasible manufacturing logistics, and bioactivities with precise physicochemical cues defined to guide cell activities for arterial regeneration. Such needs instigated our fabrication of vascular grafts, which consist of coaxial, nanostructured fibers exhibiting a polycaprolactone (PCL) core and a photoclickable, 4-arm thiolated polyethylene glycol-norbornene (PEG-NB) sheath. The graft strength and bioactivity were modulated by the PCL concentration and the peptides (RGD, transforming growth factor β-1 or TGF-β1) conjugated to thiol-ene of PEG-NB, respectively. Structural, physical, and mechanical characterizations demonstrated that the fibrous grafts mimicked the key features of the native extracellular matrix, including a crosslinked fiber network for structural stability, viscoelasticity emulating arteries, hydration property, and high porosity for cell infiltration. Meanwhile, these grafts displayed strength and toughness exceeding or meeting surgical criteria. Furthermore, the grafts with higher PCL concentration (3 vs 1.8%) showed thicker fibers, lower porosity and pore size, and increased elastic and storage moduli. Graft bioactivity was determined by the mesenchymal stem cell (MSC) behaviors on the grafts and arterial regeneration in vivo using interposition grafting. Results showed that the cell adhesion and proliferation increased with the RGD density (25 vs 5 mM). After 1 week implantation, all peptide-functionalized PCL/PEG-NB grafts with or without MSC preseeding, as opposed to PCL grafts, showed expeditious endothelial lining, abundant vascular cell infiltration, and matrix production. Compared to RGD grafts, RGD/TGF-β1 grafts enhanced MSC differentiation into smooth muscle cells in vitro and developed thicker smooth muscle cell layers in vivo. Overall, the versatile porous vascular grafts offer superior properties and tunability for future translation.
KW - coaxial electrospun fiber
KW - multi-armed polymer
KW - polyethylene glycol-norbornene
KW - regeneration
KW - stiffness
KW - vascular graft
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U2 - 10.1021/acsabm.0c01114
DO - 10.1021/acsabm.0c01114
M3 - Article
C2 - 34458689
AN - SCOPUS:85099066519
SN - 2576-6422
VL - 4
SP - 545
EP - 558
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
IS - 1
ER -