Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation

Ruth R. Chen, Eduardo Silva, William W. Yuen, David J. Mooney

Research output: Contribution to journalArticle

259 Citations (Scopus)

Abstract

Purpose. Biological mechanisms of tissue regeneration are often complex, involving the tightly coordinated spatial and temporal presentation of multiple factors. We investigated whether spatially compartmentalized and sequential delivery of factors can be used to pattern new blood vessel formation. Materials and Methods. A porous bi-layered poly(lactide-co-glycolide) (PLG) scaffold system was used to locally present vascular endothelial growth factor (VEGF) alone in one spatial region, and sequentially deliver VEGF and platelet-derived growth factor (PDGF) in an adjacent region. Scaffolds were implanted in severely ischemic hindlimbs of SCID mice for 2 and 6 weeks, and new vessel formation was quantified within the scaffolds. Results. In the compartment delivering a high dose of VEGF alone, a high density of small, immature blood vessels was observed at 2 weeks. Sequential delivery of VEGF and PDGF led to a slightly lower blood vessel density, but vessel size and maturity were significantly enhanced. Results were similar at 6 weeks, with continued remodeling of vessels in the VEGF and PDGF layer towards increased size and maturation. Conclusions. Spatially localizing and temporally controlling growth factor presentation for angiogenesis can create spatially organized tissues.

Original languageEnglish (US)
Pages (from-to)258-264
Number of pages7
JournalPharmaceutical Research
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

Fingerprint

Platelet-Derived Growth Factor
Blood vessels
Vascular Endothelial Growth Factor A
Blood Vessels
Scaffolds
Polyglactin 910
Tissue regeneration
SCID Mice
Hindlimb
Regeneration
Intercellular Signaling Peptides and Proteins
Tissue

Keywords

  • Angiogenesis
  • Controlled drug delivery
  • PDGF
  • Vascular remodeling
  • VEGF

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation. / Chen, Ruth R.; Silva, Eduardo; Yuen, William W.; Mooney, David J.

In: Pharmaceutical Research, Vol. 24, No. 2, 01.02.2007, p. 258-264.

Research output: Contribution to journalArticle

Chen, Ruth R. ; Silva, Eduardo ; Yuen, William W. ; Mooney, David J. / Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation. In: Pharmaceutical Research. 2007 ; Vol. 24, No. 2. pp. 258-264.
@article{7ab12db5c50e41fd8b74eacf1ed2bf1a,
title = "Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation",
abstract = "Purpose. Biological mechanisms of tissue regeneration are often complex, involving the tightly coordinated spatial and temporal presentation of multiple factors. We investigated whether spatially compartmentalized and sequential delivery of factors can be used to pattern new blood vessel formation. Materials and Methods. A porous bi-layered poly(lactide-co-glycolide) (PLG) scaffold system was used to locally present vascular endothelial growth factor (VEGF) alone in one spatial region, and sequentially deliver VEGF and platelet-derived growth factor (PDGF) in an adjacent region. Scaffolds were implanted in severely ischemic hindlimbs of SCID mice for 2 and 6 weeks, and new vessel formation was quantified within the scaffolds. Results. In the compartment delivering a high dose of VEGF alone, a high density of small, immature blood vessels was observed at 2 weeks. Sequential delivery of VEGF and PDGF led to a slightly lower blood vessel density, but vessel size and maturity were significantly enhanced. Results were similar at 6 weeks, with continued remodeling of vessels in the VEGF and PDGF layer towards increased size and maturation. Conclusions. Spatially localizing and temporally controlling growth factor presentation for angiogenesis can create spatially organized tissues.",
keywords = "Angiogenesis, Controlled drug delivery, PDGF, Vascular remodeling, VEGF",
author = "Chen, {Ruth R.} and Eduardo Silva and Yuen, {William W.} and Mooney, {David J.}",
year = "2007",
month = "2",
day = "1",
doi = "10.1007/s11095-006-9173-4",
language = "English (US)",
volume = "24",
pages = "258--264",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation

AU - Chen, Ruth R.

AU - Silva, Eduardo

AU - Yuen, William W.

AU - Mooney, David J.

PY - 2007/2/1

Y1 - 2007/2/1

N2 - Purpose. Biological mechanisms of tissue regeneration are often complex, involving the tightly coordinated spatial and temporal presentation of multiple factors. We investigated whether spatially compartmentalized and sequential delivery of factors can be used to pattern new blood vessel formation. Materials and Methods. A porous bi-layered poly(lactide-co-glycolide) (PLG) scaffold system was used to locally present vascular endothelial growth factor (VEGF) alone in one spatial region, and sequentially deliver VEGF and platelet-derived growth factor (PDGF) in an adjacent region. Scaffolds were implanted in severely ischemic hindlimbs of SCID mice for 2 and 6 weeks, and new vessel formation was quantified within the scaffolds. Results. In the compartment delivering a high dose of VEGF alone, a high density of small, immature blood vessels was observed at 2 weeks. Sequential delivery of VEGF and PDGF led to a slightly lower blood vessel density, but vessel size and maturity were significantly enhanced. Results were similar at 6 weeks, with continued remodeling of vessels in the VEGF and PDGF layer towards increased size and maturation. Conclusions. Spatially localizing and temporally controlling growth factor presentation for angiogenesis can create spatially organized tissues.

AB - Purpose. Biological mechanisms of tissue regeneration are often complex, involving the tightly coordinated spatial and temporal presentation of multiple factors. We investigated whether spatially compartmentalized and sequential delivery of factors can be used to pattern new blood vessel formation. Materials and Methods. A porous bi-layered poly(lactide-co-glycolide) (PLG) scaffold system was used to locally present vascular endothelial growth factor (VEGF) alone in one spatial region, and sequentially deliver VEGF and platelet-derived growth factor (PDGF) in an adjacent region. Scaffolds were implanted in severely ischemic hindlimbs of SCID mice for 2 and 6 weeks, and new vessel formation was quantified within the scaffolds. Results. In the compartment delivering a high dose of VEGF alone, a high density of small, immature blood vessels was observed at 2 weeks. Sequential delivery of VEGF and PDGF led to a slightly lower blood vessel density, but vessel size and maturity were significantly enhanced. Results were similar at 6 weeks, with continued remodeling of vessels in the VEGF and PDGF layer towards increased size and maturation. Conclusions. Spatially localizing and temporally controlling growth factor presentation for angiogenesis can create spatially organized tissues.

KW - Angiogenesis

KW - Controlled drug delivery

KW - PDGF

KW - Vascular remodeling

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=33846050010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846050010&partnerID=8YFLogxK

U2 - 10.1007/s11095-006-9173-4

DO - 10.1007/s11095-006-9173-4

M3 - Article

C2 - 17191092

AN - SCOPUS:33846050010

VL - 24

SP - 258

EP - 264

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 2

ER -