Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering

Yonggang Pang, Xiaoli Wang, Areck A. Ucuzian, Eric M. Brey, Wilson H. Burgess, Kathryn J. Jones, Thomas D. Alexander, Howard P. Greisler

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

We investigated the delivery of R136K-CBD (a collagen-binding mutant chimera of fibroblast growth factor-1) with a type I collagen scaffold as the delivery vehicle to smooth muscle cells (SMCs) for vascular tissue engineering. The binding affinity of R136K-CBD to 3-D collagen scaffolds was investigated both in the presence and absence of cells and/or salts. 2-D and 3-D visualization of delivery of R136K-CBD into SMCs were accomplished by combined fluorescent and reflection confocal microscopy. The mitogenic effect of collagen-immobilized R136K-CBD on SMCs in 3-D collagen was studied by Cyquant assay at different time intervals. In the group devoid of salt and cells, no detectable release of R136K-CBD into overlying culture media was found, compared with burst-and-continuous release of R136K and FGF-1 over a 14-day period in all other groups. The release rate of R136K-CBD was 1.7 and 1.6-fold less than R-136K and FGF-1 when media was supplemented with 2 m salt (P < 0.0001), and 2.6 and 2.5-fold less in cell-populated collagen hydrogels (P < 0.0001), respectively. R136K-CBD showed essentially uniform binding to collagen and its distribution was dependent on that of the collagen scaffold. Internalization of R136K-CBD into SMCs was documented by confocal microscopy. 3-D local delivery of collagen-immobilized R136K-CBD increased the proliferation of SMCs in the collagen matrix to significantly greater levels and for a significantly greater duration than R136K or FGF-1, with 2.0 and 2.1-fold more mitogenicity than R136K and FGF-1 respectively (P < 0.0001) at day 7. The results suggest that our collagen-binding fusion protein is an effective strategy for growth factor delivery for vascular tissue engineering.

Original languageEnglish (US)
Pages (from-to)878-885
Number of pages8
JournalBiomaterials
Volume31
Issue number5
DOIs
StatePublished - Feb 1 2010

Fingerprint

Fibroblast Growth Factor 1
Tissue Engineering
Scaffolds (biology)
Tissue engineering
Collagen
Smooth Muscle Myocytes
Blood Vessels
Muscle
Cells
Scaffolds
Salts
Confocal microscopy
Confocal Microscopy
Hydrogels
Collagen Type I
Fibroblasts
Culture Media
Assays
Intercellular Signaling Peptides and Proteins
Carrier Proteins

Keywords

  • Cell proliferation
  • Collagen
  • Controlled drug release
  • Growth factors
  • Smooth muscle cell

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering. / Pang, Yonggang; Wang, Xiaoli; Ucuzian, Areck A.; Brey, Eric M.; Burgess, Wilson H.; Jones, Kathryn J.; Alexander, Thomas D.; Greisler, Howard P.

In: Biomaterials, Vol. 31, No. 5, 01.02.2010, p. 878-885.

Research output: Contribution to journalArticle

Pang, Yonggang ; Wang, Xiaoli ; Ucuzian, Areck A. ; Brey, Eric M. ; Burgess, Wilson H. ; Jones, Kathryn J. ; Alexander, Thomas D. ; Greisler, Howard P. / Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering. In: Biomaterials. 2010 ; Vol. 31, No. 5. pp. 878-885.
@article{29478a73de1a496db3140ff676815cec,
title = "Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering",
abstract = "We investigated the delivery of R136K-CBD (a collagen-binding mutant chimera of fibroblast growth factor-1) with a type I collagen scaffold as the delivery vehicle to smooth muscle cells (SMCs) for vascular tissue engineering. The binding affinity of R136K-CBD to 3-D collagen scaffolds was investigated both in the presence and absence of cells and/or salts. 2-D and 3-D visualization of delivery of R136K-CBD into SMCs were accomplished by combined fluorescent and reflection confocal microscopy. The mitogenic effect of collagen-immobilized R136K-CBD on SMCs in 3-D collagen was studied by Cyquant assay at different time intervals. In the group devoid of salt and cells, no detectable release of R136K-CBD into overlying culture media was found, compared with burst-and-continuous release of R136K and FGF-1 over a 14-day period in all other groups. The release rate of R136K-CBD was 1.7 and 1.6-fold less than R-136K and FGF-1 when media was supplemented with 2 m salt (P < 0.0001), and 2.6 and 2.5-fold less in cell-populated collagen hydrogels (P < 0.0001), respectively. R136K-CBD showed essentially uniform binding to collagen and its distribution was dependent on that of the collagen scaffold. Internalization of R136K-CBD into SMCs was documented by confocal microscopy. 3-D local delivery of collagen-immobilized R136K-CBD increased the proliferation of SMCs in the collagen matrix to significantly greater levels and for a significantly greater duration than R136K or FGF-1, with 2.0 and 2.1-fold more mitogenicity than R136K and FGF-1 respectively (P < 0.0001) at day 7. The results suggest that our collagen-binding fusion protein is an effective strategy for growth factor delivery for vascular tissue engineering.",
keywords = "Cell proliferation, Collagen, Controlled drug release, Growth factors, Smooth muscle cell",
author = "Yonggang Pang and Xiaoli Wang and Ucuzian, {Areck A.} and Brey, {Eric M.} and Burgess, {Wilson H.} and Jones, {Kathryn J.} and Alexander, {Thomas D.} and Greisler, {Howard P.}",
year = "2010",
month = "2",
day = "1",
doi = "10.1016/j.biomaterials.2009.10.007",
language = "English (US)",
volume = "31",
pages = "878--885",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "5",

}

TY - JOUR

T1 - Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering

AU - Pang, Yonggang

AU - Wang, Xiaoli

AU - Ucuzian, Areck A.

AU - Brey, Eric M.

AU - Burgess, Wilson H.

AU - Jones, Kathryn J.

AU - Alexander, Thomas D.

AU - Greisler, Howard P.

PY - 2010/2/1

Y1 - 2010/2/1

N2 - We investigated the delivery of R136K-CBD (a collagen-binding mutant chimera of fibroblast growth factor-1) with a type I collagen scaffold as the delivery vehicle to smooth muscle cells (SMCs) for vascular tissue engineering. The binding affinity of R136K-CBD to 3-D collagen scaffolds was investigated both in the presence and absence of cells and/or salts. 2-D and 3-D visualization of delivery of R136K-CBD into SMCs were accomplished by combined fluorescent and reflection confocal microscopy. The mitogenic effect of collagen-immobilized R136K-CBD on SMCs in 3-D collagen was studied by Cyquant assay at different time intervals. In the group devoid of salt and cells, no detectable release of R136K-CBD into overlying culture media was found, compared with burst-and-continuous release of R136K and FGF-1 over a 14-day period in all other groups. The release rate of R136K-CBD was 1.7 and 1.6-fold less than R-136K and FGF-1 when media was supplemented with 2 m salt (P < 0.0001), and 2.6 and 2.5-fold less in cell-populated collagen hydrogels (P < 0.0001), respectively. R136K-CBD showed essentially uniform binding to collagen and its distribution was dependent on that of the collagen scaffold. Internalization of R136K-CBD into SMCs was documented by confocal microscopy. 3-D local delivery of collagen-immobilized R136K-CBD increased the proliferation of SMCs in the collagen matrix to significantly greater levels and for a significantly greater duration than R136K or FGF-1, with 2.0 and 2.1-fold more mitogenicity than R136K and FGF-1 respectively (P < 0.0001) at day 7. The results suggest that our collagen-binding fusion protein is an effective strategy for growth factor delivery for vascular tissue engineering.

AB - We investigated the delivery of R136K-CBD (a collagen-binding mutant chimera of fibroblast growth factor-1) with a type I collagen scaffold as the delivery vehicle to smooth muscle cells (SMCs) for vascular tissue engineering. The binding affinity of R136K-CBD to 3-D collagen scaffolds was investigated both in the presence and absence of cells and/or salts. 2-D and 3-D visualization of delivery of R136K-CBD into SMCs were accomplished by combined fluorescent and reflection confocal microscopy. The mitogenic effect of collagen-immobilized R136K-CBD on SMCs in 3-D collagen was studied by Cyquant assay at different time intervals. In the group devoid of salt and cells, no detectable release of R136K-CBD into overlying culture media was found, compared with burst-and-continuous release of R136K and FGF-1 over a 14-day period in all other groups. The release rate of R136K-CBD was 1.7 and 1.6-fold less than R-136K and FGF-1 when media was supplemented with 2 m salt (P < 0.0001), and 2.6 and 2.5-fold less in cell-populated collagen hydrogels (P < 0.0001), respectively. R136K-CBD showed essentially uniform binding to collagen and its distribution was dependent on that of the collagen scaffold. Internalization of R136K-CBD into SMCs was documented by confocal microscopy. 3-D local delivery of collagen-immobilized R136K-CBD increased the proliferation of SMCs in the collagen matrix to significantly greater levels and for a significantly greater duration than R136K or FGF-1, with 2.0 and 2.1-fold more mitogenicity than R136K and FGF-1 respectively (P < 0.0001) at day 7. The results suggest that our collagen-binding fusion protein is an effective strategy for growth factor delivery for vascular tissue engineering.

KW - Cell proliferation

KW - Collagen

KW - Controlled drug release

KW - Growth factors

KW - Smooth muscle cell

UR - http://www.scopus.com/inward/record.url?scp=70649111286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70649111286&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2009.10.007

DO - 10.1016/j.biomaterials.2009.10.007

M3 - Article

C2 - 19853908

AN - SCOPUS:70649111286

VL - 31

SP - 878

EP - 885

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 5

ER -