Abstract
The development of cell-free vascular grafts has tremendous potential for tissue engineering. However, thrombus formation, less-than-ideal cell infiltration, and a lack of growth potential limit the application of electrospun scaffolds for in situ tissue-engineered vasculature. To overcome these challenges, here we present development of an acellular tissue-engineered vessel based on electrospun poly(L-lactide-co-e-caprolactone) scaffolds. Heparin was conjugated to suppress thrombogenic responses, and substance P (SP) was immobilized to recruit host cells. SP was released in a sustained manner from scaffolds and recruited human bone marrow-derived mesenchymal stem cells. The biocompatibility and biological performance of the grafts were evaluated by in vivo experiments involving subcutaneous scaffold implantation in Sprague-Dawley rats (n=12) for up to 4 weeks. Histological analysis revealed a higher extent of accumulative host cell infiltration, neotissue formation, collagen deposition, and elastin deposition in scaffolds containing either SP or heparin/SP than in the control groups. We also observed the presence of a large number of laminin-positive blood vessels, von Willebrand factor (vWF+) cells, and alpha smooth muscle actin-positive cells in the explants containing SP and heparin/SP. Additionally, SP and heparin/SP grafts showed the existence of CD90+ and CD105+ MSCs and induced a large number of M2 macrophages to infiltrate the graft wall compared with that observed with the control group. Our cell-free grafts could enhance vascular regeneration by endogenous cell recruitment and by mediating macrophage polarization into the M2 phenotype, suggesting that these constructs may be a promising cell-free graft candidate and are worthy of further in vivo evaluation.
| Original language | English |
|---|---|
| Journal | Journal of Biomedical Materials Research - Part A |
| DOIs | |
| Publication status | Accepted/In press - 2016 |
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Keywords
- Electrospinning
- in situ tissue regeneration
- Neovascularization/angiogenesis
- Stem cell
- Vascular graft
ASJC Scopus subject areas
- Biomedical Engineering
- Biomaterials
- Ceramics and Composites
- Metals and Alloys
Cite this
Covalent immobilization of stem cell inducing/recruiting factor and heparin on cell-free small-diameter vascular graft for accelerated in situ tissue regeneration. / Shafiq, Muhammad; Jung, Youngmee; Kim, Soo Hyun.
In: Journal of Biomedical Materials Research - Part A, 2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Covalent immobilization of stem cell inducing/recruiting factor and heparin on cell-free small-diameter vascular graft for accelerated in situ tissue regeneration
AU - Shafiq, Muhammad
AU - Jung, Youngmee
AU - Kim, Soo Hyun
PY - 2016
Y1 - 2016
N2 - The development of cell-free vascular grafts has tremendous potential for tissue engineering. However, thrombus formation, less-than-ideal cell infiltration, and a lack of growth potential limit the application of electrospun scaffolds for in situ tissue-engineered vasculature. To overcome these challenges, here we present development of an acellular tissue-engineered vessel based on electrospun poly(L-lactide-co-e-caprolactone) scaffolds. Heparin was conjugated to suppress thrombogenic responses, and substance P (SP) was immobilized to recruit host cells. SP was released in a sustained manner from scaffolds and recruited human bone marrow-derived mesenchymal stem cells. The biocompatibility and biological performance of the grafts were evaluated by in vivo experiments involving subcutaneous scaffold implantation in Sprague-Dawley rats (n=12) for up to 4 weeks. Histological analysis revealed a higher extent of accumulative host cell infiltration, neotissue formation, collagen deposition, and elastin deposition in scaffolds containing either SP or heparin/SP than in the control groups. We also observed the presence of a large number of laminin-positive blood vessels, von Willebrand factor (vWF+) cells, and alpha smooth muscle actin-positive cells in the explants containing SP and heparin/SP. Additionally, SP and heparin/SP grafts showed the existence of CD90+ and CD105+ MSCs and induced a large number of M2 macrophages to infiltrate the graft wall compared with that observed with the control group. Our cell-free grafts could enhance vascular regeneration by endogenous cell recruitment and by mediating macrophage polarization into the M2 phenotype, suggesting that these constructs may be a promising cell-free graft candidate and are worthy of further in vivo evaluation.
AB - The development of cell-free vascular grafts has tremendous potential for tissue engineering. However, thrombus formation, less-than-ideal cell infiltration, and a lack of growth potential limit the application of electrospun scaffolds for in situ tissue-engineered vasculature. To overcome these challenges, here we present development of an acellular tissue-engineered vessel based on electrospun poly(L-lactide-co-e-caprolactone) scaffolds. Heparin was conjugated to suppress thrombogenic responses, and substance P (SP) was immobilized to recruit host cells. SP was released in a sustained manner from scaffolds and recruited human bone marrow-derived mesenchymal stem cells. The biocompatibility and biological performance of the grafts were evaluated by in vivo experiments involving subcutaneous scaffold implantation in Sprague-Dawley rats (n=12) for up to 4 weeks. Histological analysis revealed a higher extent of accumulative host cell infiltration, neotissue formation, collagen deposition, and elastin deposition in scaffolds containing either SP or heparin/SP than in the control groups. We also observed the presence of a large number of laminin-positive blood vessels, von Willebrand factor (vWF+) cells, and alpha smooth muscle actin-positive cells in the explants containing SP and heparin/SP. Additionally, SP and heparin/SP grafts showed the existence of CD90+ and CD105+ MSCs and induced a large number of M2 macrophages to infiltrate the graft wall compared with that observed with the control group. Our cell-free grafts could enhance vascular regeneration by endogenous cell recruitment and by mediating macrophage polarization into the M2 phenotype, suggesting that these constructs may be a promising cell-free graft candidate and are worthy of further in vivo evaluation.
KW - Electrospinning
KW - in situ tissue regeneration
KW - Neovascularization/angiogenesis
KW - Stem cell
KW - Vascular graft
UR - http://www.scopus.com/inward/record.url?scp=84977858260&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84977858260&partnerID=8YFLogxK
U2 - 10.1002/jbm.a.35666
DO - 10.1002/jbm.a.35666
M3 - Article
C2 - 26822178
AN - SCOPUS:84977858260
JO - Journal of Biomedical Materials Research - Part A
JF - Journal of Biomedical Materials Research - Part A
SN - 0021-9304
ER -