The effect of sustained delivery of vascular endothelial growth factor on angiogenesis in tissue-engineered intestine

Flavio G. Rocha, Cathryn A. Sundback, Nicholas J. Krebs, Jonathan K Leach, David J. Mooney, Stanley W. Ashley, Joseph P. Vacanti, Edward E. Whang

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Our group has previously created a functional neointestine that is capable of restoring absorptive function. However, the endogenous level of vascular endothelial growth factor (VEGF) is markedly reduced in the construct compared to native bowel. Therefore, we wanted to locally deliver VEGF in a sustained fashion to upregulate angiogenesis in the neointestine. Rat recombinant VEGF was encapsulated in poly(lactide-co-glycolide) microspheres by a double emulsion method. Release kinetics and bioactivity were determined in vitro. Tissue-engineered intestine was generated by seeding donor neonatal rat intestinal organoid units onto a biodegradable polyglycolic acid scaffold along with VEGF-containing or empty microspheres, and wrapped in the omentum of recipient rats. After 4 weeks, the neointestinal cysts were analyzed for morphometry, VEGF levels, epithelial proliferation, and capillary density. Sustained release of biologically active VEGF was confirmed by in vitro studies. Intestinal constructs with VEGF microspheres were significantly larger than those containing empty microspheres. Tissue VEGF levels were significantly higher in neointestine loaded with encapsulated VEGF compared to those without growth factor. Epithelial cellular proliferation and capillary density were significantly increased in the VEGF-containing neointestinal constructs compared to empty constructs. Tissue-engineered intestine responds to sustained delivery of VEGF by upregulating microvasculature and epithelial proliferation.

Original languageEnglish (US)
Pages (from-to)2884-2890
Number of pages7
JournalBiomaterials
Volume29
Issue number19
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Intestines
Tissue
Microspheres
Rats
Intercellular Signaling Peptides and Proteins
Organoids
Polyglycolic Acid
Polyglactin 910
Omentum
Microvessels
Bioactivity
Emulsions
Scaffolds
Cysts
Up-Regulation
Cell Proliferation
Kinetics
Acids

Keywords

  • Angiogenesis
  • Microspheres
  • PLGA
  • Small intestine
  • VEGF

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Rocha, F. G., Sundback, C. A., Krebs, N. J., Leach, J. K., Mooney, D. J., Ashley, S. W., ... Whang, E. E. (2008). The effect of sustained delivery of vascular endothelial growth factor on angiogenesis in tissue-engineered intestine. Biomaterials, 29(19), 2884-2890. https://doi.org/10.1016/j.biomaterials.2008.03.026

The effect of sustained delivery of vascular endothelial growth factor on angiogenesis in tissue-engineered intestine. / Rocha, Flavio G.; Sundback, Cathryn A.; Krebs, Nicholas J.; Leach, Jonathan K; Mooney, David J.; Ashley, Stanley W.; Vacanti, Joseph P.; Whang, Edward E.

In: Biomaterials, Vol. 29, No. 19, 07.2008, p. 2884-2890.

Research output: Contribution to journalArticle

Rocha, FG, Sundback, CA, Krebs, NJ, Leach, JK, Mooney, DJ, Ashley, SW, Vacanti, JP & Whang, EE 2008, 'The effect of sustained delivery of vascular endothelial growth factor on angiogenesis in tissue-engineered intestine', Biomaterials, vol. 29, no. 19, pp. 2884-2890. https://doi.org/10.1016/j.biomaterials.2008.03.026
Rocha, Flavio G. ; Sundback, Cathryn A. ; Krebs, Nicholas J. ; Leach, Jonathan K ; Mooney, David J. ; Ashley, Stanley W. ; Vacanti, Joseph P. ; Whang, Edward E. / The effect of sustained delivery of vascular endothelial growth factor on angiogenesis in tissue-engineered intestine. In: Biomaterials. 2008 ; Vol. 29, No. 19. pp. 2884-2890.
@article{8eb2bbd7b25f483f83a685272466a646,
title = "The effect of sustained delivery of vascular endothelial growth factor on angiogenesis in tissue-engineered intestine",
abstract = "Our group has previously created a functional neointestine that is capable of restoring absorptive function. However, the endogenous level of vascular endothelial growth factor (VEGF) is markedly reduced in the construct compared to native bowel. Therefore, we wanted to locally deliver VEGF in a sustained fashion to upregulate angiogenesis in the neointestine. Rat recombinant VEGF was encapsulated in poly(lactide-co-glycolide) microspheres by a double emulsion method. Release kinetics and bioactivity were determined in vitro. Tissue-engineered intestine was generated by seeding donor neonatal rat intestinal organoid units onto a biodegradable polyglycolic acid scaffold along with VEGF-containing or empty microspheres, and wrapped in the omentum of recipient rats. After 4 weeks, the neointestinal cysts were analyzed for morphometry, VEGF levels, epithelial proliferation, and capillary density. Sustained release of biologically active VEGF was confirmed by in vitro studies. Intestinal constructs with VEGF microspheres were significantly larger than those containing empty microspheres. Tissue VEGF levels were significantly higher in neointestine loaded with encapsulated VEGF compared to those without growth factor. Epithelial cellular proliferation and capillary density were significantly increased in the VEGF-containing neointestinal constructs compared to empty constructs. Tissue-engineered intestine responds to sustained delivery of VEGF by upregulating microvasculature and epithelial proliferation.",
keywords = "Angiogenesis, Microspheres, PLGA, Small intestine, VEGF",
author = "Rocha, {Flavio G.} and Sundback, {Cathryn A.} and Krebs, {Nicholas J.} and Leach, {Jonathan K} and Mooney, {David J.} and Ashley, {Stanley W.} and Vacanti, {Joseph P.} and Whang, {Edward E.}",
year = "2008",
month = "7",
doi = "10.1016/j.biomaterials.2008.03.026",
language = "English (US)",
volume = "29",
pages = "2884--2890",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "19",

}

TY - JOUR

T1 - The effect of sustained delivery of vascular endothelial growth factor on angiogenesis in tissue-engineered intestine

AU - Rocha, Flavio G.

AU - Sundback, Cathryn A.

AU - Krebs, Nicholas J.

AU - Leach, Jonathan K

AU - Mooney, David J.

AU - Ashley, Stanley W.

AU - Vacanti, Joseph P.

AU - Whang, Edward E.

PY - 2008/7

Y1 - 2008/7

N2 - Our group has previously created a functional neointestine that is capable of restoring absorptive function. However, the endogenous level of vascular endothelial growth factor (VEGF) is markedly reduced in the construct compared to native bowel. Therefore, we wanted to locally deliver VEGF in a sustained fashion to upregulate angiogenesis in the neointestine. Rat recombinant VEGF was encapsulated in poly(lactide-co-glycolide) microspheres by a double emulsion method. Release kinetics and bioactivity were determined in vitro. Tissue-engineered intestine was generated by seeding donor neonatal rat intestinal organoid units onto a biodegradable polyglycolic acid scaffold along with VEGF-containing or empty microspheres, and wrapped in the omentum of recipient rats. After 4 weeks, the neointestinal cysts were analyzed for morphometry, VEGF levels, epithelial proliferation, and capillary density. Sustained release of biologically active VEGF was confirmed by in vitro studies. Intestinal constructs with VEGF microspheres were significantly larger than those containing empty microspheres. Tissue VEGF levels were significantly higher in neointestine loaded with encapsulated VEGF compared to those without growth factor. Epithelial cellular proliferation and capillary density were significantly increased in the VEGF-containing neointestinal constructs compared to empty constructs. Tissue-engineered intestine responds to sustained delivery of VEGF by upregulating microvasculature and epithelial proliferation.

AB - Our group has previously created a functional neointestine that is capable of restoring absorptive function. However, the endogenous level of vascular endothelial growth factor (VEGF) is markedly reduced in the construct compared to native bowel. Therefore, we wanted to locally deliver VEGF in a sustained fashion to upregulate angiogenesis in the neointestine. Rat recombinant VEGF was encapsulated in poly(lactide-co-glycolide) microspheres by a double emulsion method. Release kinetics and bioactivity were determined in vitro. Tissue-engineered intestine was generated by seeding donor neonatal rat intestinal organoid units onto a biodegradable polyglycolic acid scaffold along with VEGF-containing or empty microspheres, and wrapped in the omentum of recipient rats. After 4 weeks, the neointestinal cysts were analyzed for morphometry, VEGF levels, epithelial proliferation, and capillary density. Sustained release of biologically active VEGF was confirmed by in vitro studies. Intestinal constructs with VEGF microspheres were significantly larger than those containing empty microspheres. Tissue VEGF levels were significantly higher in neointestine loaded with encapsulated VEGF compared to those without growth factor. Epithelial cellular proliferation and capillary density were significantly increased in the VEGF-containing neointestinal constructs compared to empty constructs. Tissue-engineered intestine responds to sustained delivery of VEGF by upregulating microvasculature and epithelial proliferation.

KW - Angiogenesis

KW - Microspheres

KW - PLGA

KW - Small intestine

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=42249103434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42249103434&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2008.03.026

DO - 10.1016/j.biomaterials.2008.03.026

M3 - Article

C2 - 18396329

AN - SCOPUS:42249103434

VL - 29

SP - 2884

EP - 2890

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 19

ER -