A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants

Adinarayana Andukuri; Meenakshi Kushwaha; Ajay Tambralli; Joel M. Anderson; Derrick R. Dean; Joel L. Berry; Young Doug Sohn; Young Sup Yoon; Brigitta C. Brott; Ho Wook Jun

doi:10.1016/j.actbio.2010.08.013

A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants

Adinarayana Andukuri, Meenakshi Kushwaha, Ajay Tambralli, Joel M. Anderson, Derrick R. Dean, Joel L. Berry, Young Doug Sohn, Young Sup Yoon, Brigitta C. Brott, Ho Wook Jun

BioMedical Science Institute

Research output: Contribution to journal › Article › peer-review

70 Citations (Scopus)

Abstract

Current cardiovascular therapies are limited by the loss of endothelium, restenosis and thrombosis. The goal of this study was to develop a biomimetic hybrid nanomatrix that combined the unique properties of electrospun polycaprolactone (ePCL) nanofibers with self-assembled peptide amphiphiles (PAs). ePCL nanofibers have interconnected nanoporous structures, but are hampered by a lack of surface bioactivity to control cellular behavior. It has been hypothesized that PAs could self-assemble onto the surface of ePCL nanofibers and endow them with the characteristic properties of native endothelium. The PAs, which comprised hydrophobic alkyl tails attached to functional hydrophilic peptide sequences, contained enzyme-mediated degradable sites coupled to either endothelial cell-adhesive ligands (YIGSR) or polylysine (KKKKK) nitric oxide (NO) donors. Two different PAs (PA-YIGSR and PA-KKKKK) were successfully synthesized and mixed in a 90:10 (YK) ratio to obtain PA-YK. PA-YK was reacted with pure NO to develop PA-YK-NO, which was then self-assembled onto ePCL nanofibers to generate a hybrid nanomatrix, ePCL-PA-YK-NO. Uniform coating of self-assembled PA nanofibers on ePCL was confirmed by transmission electron microscopy. Successful NO release from ePCL-PA-YK-NO was observed. ePCL-YK and ePCL-PA-YK-NO showed significantly increased adhesion of human umbilical vein endothelial cells (HUVECs). ePCL-PA-YK-NO also showed significantly increased proliferation of HUVECs and reduced smooth muscle cell proliferation. ePCL-PA-YK-NO also displayed significantly reduced platelet adhesion compared with ePCL, ePCL-PA-YK and a collagen control. These results indicate that this hybrid nanomatrix has great potential application in cardiovascular implants.

Original language	English
Pages (from-to)	225-233
Number of pages	9
Journal	Acta Biomaterialia
Volume	7
Issue number	1
DOIs	https://doi.org/10.1016/j.actbio.2010.08.013
Publication status	Published - 2011 Jan

Bibliographical note

Funding Information:
The authors express their gratitude to Melissa Chimento for use of the High Resolution Imaging facility and Dr Robin G. Foley for use of the Scanning Electron Microscopic facility. This study was supported by the Wallace H. Coulter Foundation and a NSF Career Award (CBET-0952974) (H.W.J.), a Caroline P. Ireland Research Scholarship (A.A. and M.K.), a AHA Greater Southeast Affiliate Predoctoral Fellowship (10PRE3500024) (A.A.), a NIH T32 Predoctoral Training Grant (NIBIB EB004312-01 ) and a Ruth L. Kirschstein National Research Service Award Individual Fellowship ( 1F31DE021286-01 ) (J.M.A.).

All Science Journal Classification (ASJC) codes

Biotechnology
Biomaterials
Biochemistry
Biomedical Engineering
Molecular Biology

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10.1016/j.actbio.2010.08.013

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title = "A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants",

abstract = "Current cardiovascular therapies are limited by the loss of endothelium, restenosis and thrombosis. The goal of this study was to develop a biomimetic hybrid nanomatrix that combined the unique properties of electrospun polycaprolactone (ePCL) nanofibers with self-assembled peptide amphiphiles (PAs). ePCL nanofibers have interconnected nanoporous structures, but are hampered by a lack of surface bioactivity to control cellular behavior. It has been hypothesized that PAs could self-assemble onto the surface of ePCL nanofibers and endow them with the characteristic properties of native endothelium. The PAs, which comprised hydrophobic alkyl tails attached to functional hydrophilic peptide sequences, contained enzyme-mediated degradable sites coupled to either endothelial cell-adhesive ligands (YIGSR) or polylysine (KKKKK) nitric oxide (NO) donors. Two different PAs (PA-YIGSR and PA-KKKKK) were successfully synthesized and mixed in a 90:10 (YK) ratio to obtain PA-YK. PA-YK was reacted with pure NO to develop PA-YK-NO, which was then self-assembled onto ePCL nanofibers to generate a hybrid nanomatrix, ePCL-PA-YK-NO. Uniform coating of self-assembled PA nanofibers on ePCL was confirmed by transmission electron microscopy. Successful NO release from ePCL-PA-YK-NO was observed. ePCL-YK and ePCL-PA-YK-NO showed significantly increased adhesion of human umbilical vein endothelial cells (HUVECs). ePCL-PA-YK-NO also showed significantly increased proliferation of HUVECs and reduced smooth muscle cell proliferation. ePCL-PA-YK-NO also displayed significantly reduced platelet adhesion compared with ePCL, ePCL-PA-YK and a collagen control. These results indicate that this hybrid nanomatrix has great potential application in cardiovascular implants.",

author = "Adinarayana Andukuri and Meenakshi Kushwaha and Ajay Tambralli and Anderson, {Joel M.} and Dean, {Derrick R.} and Berry, {Joel L.} and Sohn, {Young Doug} and Yoon, {Young Sup} and Brott, {Brigitta C.} and Jun, {Ho Wook}",

note = "Funding Information: The authors express their gratitude to Melissa Chimento for use of the High Resolution Imaging facility and Dr Robin G. Foley for use of the Scanning Electron Microscopic facility. This study was supported by the Wallace H. Coulter Foundation and a NSF Career Award (CBET-0952974) (H.W.J.), a Caroline P. Ireland Research Scholarship (A.A. and M.K.), a AHA Greater Southeast Affiliate Predoctoral Fellowship (10PRE3500024) (A.A.), a NIH T32 Predoctoral Training Grant (NIBIB EB004312-01 ) and a Ruth L. Kirschstein National Research Service Award Individual Fellowship ( 1F31DE021286-01 ) (J.M.A.). ",

year = "2011",

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doi = "10.1016/j.actbio.2010.08.013",

language = "English",

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AU - Andukuri, Adinarayana

AU - Kushwaha, Meenakshi

AU - Tambralli, Ajay

AU - Anderson, Joel M.

AU - Dean, Derrick R.

AU - Berry, Joel L.

AU - Sohn, Young Doug

AU - Yoon, Young Sup

AU - Brott, Brigitta C.

AU - Jun, Ho Wook

N1 - Funding Information: The authors express their gratitude to Melissa Chimento for use of the High Resolution Imaging facility and Dr Robin G. Foley for use of the Scanning Electron Microscopic facility. This study was supported by the Wallace H. Coulter Foundation and a NSF Career Award (CBET-0952974) (H.W.J.), a Caroline P. Ireland Research Scholarship (A.A. and M.K.), a AHA Greater Southeast Affiliate Predoctoral Fellowship (10PRE3500024) (A.A.), a NIH T32 Predoctoral Training Grant (NIBIB EB004312-01 ) and a Ruth L. Kirschstein National Research Service Award Individual Fellowship ( 1F31DE021286-01 ) (J.M.A.).

PY - 2011/1

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N2 - Current cardiovascular therapies are limited by the loss of endothelium, restenosis and thrombosis. The goal of this study was to develop a biomimetic hybrid nanomatrix that combined the unique properties of electrospun polycaprolactone (ePCL) nanofibers with self-assembled peptide amphiphiles (PAs). ePCL nanofibers have interconnected nanoporous structures, but are hampered by a lack of surface bioactivity to control cellular behavior. It has been hypothesized that PAs could self-assemble onto the surface of ePCL nanofibers and endow them with the characteristic properties of native endothelium. The PAs, which comprised hydrophobic alkyl tails attached to functional hydrophilic peptide sequences, contained enzyme-mediated degradable sites coupled to either endothelial cell-adhesive ligands (YIGSR) or polylysine (KKKKK) nitric oxide (NO) donors. Two different PAs (PA-YIGSR and PA-KKKKK) were successfully synthesized and mixed in a 90:10 (YK) ratio to obtain PA-YK. PA-YK was reacted with pure NO to develop PA-YK-NO, which was then self-assembled onto ePCL nanofibers to generate a hybrid nanomatrix, ePCL-PA-YK-NO. Uniform coating of self-assembled PA nanofibers on ePCL was confirmed by transmission electron microscopy. Successful NO release from ePCL-PA-YK-NO was observed. ePCL-YK and ePCL-PA-YK-NO showed significantly increased adhesion of human umbilical vein endothelial cells (HUVECs). ePCL-PA-YK-NO also showed significantly increased proliferation of HUVECs and reduced smooth muscle cell proliferation. ePCL-PA-YK-NO also displayed significantly reduced platelet adhesion compared with ePCL, ePCL-PA-YK and a collagen control. These results indicate that this hybrid nanomatrix has great potential application in cardiovascular implants.

AB - Current cardiovascular therapies are limited by the loss of endothelium, restenosis and thrombosis. The goal of this study was to develop a biomimetic hybrid nanomatrix that combined the unique properties of electrospun polycaprolactone (ePCL) nanofibers with self-assembled peptide amphiphiles (PAs). ePCL nanofibers have interconnected nanoporous structures, but are hampered by a lack of surface bioactivity to control cellular behavior. It has been hypothesized that PAs could self-assemble onto the surface of ePCL nanofibers and endow them with the characteristic properties of native endothelium. The PAs, which comprised hydrophobic alkyl tails attached to functional hydrophilic peptide sequences, contained enzyme-mediated degradable sites coupled to either endothelial cell-adhesive ligands (YIGSR) or polylysine (KKKKK) nitric oxide (NO) donors. Two different PAs (PA-YIGSR and PA-KKKKK) were successfully synthesized and mixed in a 90:10 (YK) ratio to obtain PA-YK. PA-YK was reacted with pure NO to develop PA-YK-NO, which was then self-assembled onto ePCL nanofibers to generate a hybrid nanomatrix, ePCL-PA-YK-NO. Uniform coating of self-assembled PA nanofibers on ePCL was confirmed by transmission electron microscopy. Successful NO release from ePCL-PA-YK-NO was observed. ePCL-YK and ePCL-PA-YK-NO showed significantly increased adhesion of human umbilical vein endothelial cells (HUVECs). ePCL-PA-YK-NO also showed significantly increased proliferation of HUVECs and reduced smooth muscle cell proliferation. ePCL-PA-YK-NO also displayed significantly reduced platelet adhesion compared with ePCL, ePCL-PA-YK and a collagen control. These results indicate that this hybrid nanomatrix has great potential application in cardiovascular implants.

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A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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