Controlled release of vascular endothelial growth factor using poly-lactic-co-glycolic acid microspheres: In vitro characterization and application in polycaprolactone fumarate nerve conduits

Jing Rui, Mahrokh Dadsetan, M. Brett Runge, Robert J. Spinner, Michael J Yaszemski, Anthony John Windebank, Huan D Wang

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator. Controlled release of such stimulators may enhance and guide the vascularization process, and when applied in a nerve conduit may play a role in nerve regeneration. We report the fabrication and in vitro characterization of poly-lactic-co-glycolic acid (PLGA) microspheres encapsulating VEGF and the in vivo application of nerve conduits supplemented with VEGF-containing microspheres. PLGA microspheres containing VEGF were prepared by the double emulsion-solvent evaporation technique. This yielded 83.16% of microspheres with a diameter <53 μm. VEGF content measured by ELISA indicated 93.79 ± 10.64% encapsulation efficiency. Release kinetics were characterized by an initial burst release of 67.6 ± 8.25% within the first 24 h, followed by consistent release of approximately 0.34% per day for 4 weeks. Bioactivity of the released VEGF was tested by human umbilical vein endothelial cell (HUVEC) proliferation assay. VEGF released at all time points enhanced HUVEC proliferation, confirming that VEGF retained its bioactivity throughout the 4 week time period. When the microsphere delivery system was placed in a biosynthetic nerve scaffold robust nerve regeneration was observed. This study established a novel system for controlled release of growth factors and enables in vivo studies of nerve conduits conditioned with this system.

Original languageEnglish (US)
Pages (from-to)511-518
Number of pages8
JournalActa Biomaterialia
Volume8
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Polycaprolactone
Microspheres
Vascular Endothelial Growth Factor A
Acids
Nerve Regeneration
Endothelial cells
Human Umbilical Vein Endothelial Cells
Cell proliferation
Bioactivity
Cell Proliferation
Intercellular Signaling Peptides and Proteins
Milk
polylactic acid-polyglycolic acid copolymer
poly(caprolactone fumarate)
In Vitro Techniques
Emulsions
Encapsulation
Scaffolds
Assays
Evaporation

Keywords

  • Bioactivity
  • Biodegradation
  • Microsphere
  • Poly-lactic-co-glycolic acid
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

Cite this

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title = "Controlled release of vascular endothelial growth factor using poly-lactic-co-glycolic acid microspheres: In vitro characterization and application in polycaprolactone fumarate nerve conduits",
abstract = "Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator. Controlled release of such stimulators may enhance and guide the vascularization process, and when applied in a nerve conduit may play a role in nerve regeneration. We report the fabrication and in vitro characterization of poly-lactic-co-glycolic acid (PLGA) microspheres encapsulating VEGF and the in vivo application of nerve conduits supplemented with VEGF-containing microspheres. PLGA microspheres containing VEGF were prepared by the double emulsion-solvent evaporation technique. This yielded 83.16{\%} of microspheres with a diameter <53 μm. VEGF content measured by ELISA indicated 93.79 ± 10.64{\%} encapsulation efficiency. Release kinetics were characterized by an initial burst release of 67.6 ± 8.25{\%} within the first 24 h, followed by consistent release of approximately 0.34{\%} per day for 4 weeks. Bioactivity of the released VEGF was tested by human umbilical vein endothelial cell (HUVEC) proliferation assay. VEGF released at all time points enhanced HUVEC proliferation, confirming that VEGF retained its bioactivity throughout the 4 week time period. When the microsphere delivery system was placed in a biosynthetic nerve scaffold robust nerve regeneration was observed. This study established a novel system for controlled release of growth factors and enables in vivo studies of nerve conduits conditioned with this system.",
keywords = "Bioactivity, Biodegradation, Microsphere, Poly-lactic-co-glycolic acid, Vascular endothelial growth factor",
author = "Jing Rui and Mahrokh Dadsetan and Runge, {M. Brett} and Spinner, {Robert J.} and Yaszemski, {Michael J} and Windebank, {Anthony John} and Wang, {Huan D}",
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T1 - Controlled release of vascular endothelial growth factor using poly-lactic-co-glycolic acid microspheres

T2 - In vitro characterization and application in polycaprolactone fumarate nerve conduits

AU - Rui, Jing

AU - Dadsetan, Mahrokh

AU - Runge, M. Brett

AU - Spinner, Robert J.

AU - Yaszemski, Michael J

AU - Windebank, Anthony John

AU - Wang, Huan D

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N2 - Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator. Controlled release of such stimulators may enhance and guide the vascularization process, and when applied in a nerve conduit may play a role in nerve regeneration. We report the fabrication and in vitro characterization of poly-lactic-co-glycolic acid (PLGA) microspheres encapsulating VEGF and the in vivo application of nerve conduits supplemented with VEGF-containing microspheres. PLGA microspheres containing VEGF were prepared by the double emulsion-solvent evaporation technique. This yielded 83.16% of microspheres with a diameter <53 μm. VEGF content measured by ELISA indicated 93.79 ± 10.64% encapsulation efficiency. Release kinetics were characterized by an initial burst release of 67.6 ± 8.25% within the first 24 h, followed by consistent release of approximately 0.34% per day for 4 weeks. Bioactivity of the released VEGF was tested by human umbilical vein endothelial cell (HUVEC) proliferation assay. VEGF released at all time points enhanced HUVEC proliferation, confirming that VEGF retained its bioactivity throughout the 4 week time period. When the microsphere delivery system was placed in a biosynthetic nerve scaffold robust nerve regeneration was observed. This study established a novel system for controlled release of growth factors and enables in vivo studies of nerve conduits conditioned with this system.

AB - Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator. Controlled release of such stimulators may enhance and guide the vascularization process, and when applied in a nerve conduit may play a role in nerve regeneration. We report the fabrication and in vitro characterization of poly-lactic-co-glycolic acid (PLGA) microspheres encapsulating VEGF and the in vivo application of nerve conduits supplemented with VEGF-containing microspheres. PLGA microspheres containing VEGF were prepared by the double emulsion-solvent evaporation technique. This yielded 83.16% of microspheres with a diameter <53 μm. VEGF content measured by ELISA indicated 93.79 ± 10.64% encapsulation efficiency. Release kinetics were characterized by an initial burst release of 67.6 ± 8.25% within the first 24 h, followed by consistent release of approximately 0.34% per day for 4 weeks. Bioactivity of the released VEGF was tested by human umbilical vein endothelial cell (HUVEC) proliferation assay. VEGF released at all time points enhanced HUVEC proliferation, confirming that VEGF retained its bioactivity throughout the 4 week time period. When the microsphere delivery system was placed in a biosynthetic nerve scaffold robust nerve regeneration was observed. This study established a novel system for controlled release of growth factors and enables in vivo studies of nerve conduits conditioned with this system.

KW - Bioactivity

KW - Biodegradation

KW - Microsphere

KW - Poly-lactic-co-glycolic acid

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