Pharmaceutical Research

, Volume 25, Issue 10, pp 2370–2378 | Cite as

In Vitro and In Vivo Release of Vascular Endothelial Growth Factor from Gelatin Microparticles and Biodegradable Composite Scaffolds

  • Zarana S. Patel
  • Hiroki Ueda
  • Masaya Yamamoto
  • Yasuhiko Tabata
  • Antonios G. Mikos
Research Paper

Abstract

Purpose

This work evaluated gelatin microparticles and biodegradable composite scaffolds for the controlled release of vascular endothelial growth factor (VEGF) in vitro and in vivo.

Methods

Gelatin crosslinking, VEGF dose, and buffer type were investigated for their effects on VEGF release. Release was also evaluated from microparticles confined within porous polymer scaffolds (composites). In vitro and in vivo studies were conducted using radiolabeled VEGF.

Results

The effect of VEGF dose on its fractional release from gelatin microparticles in vitro was minimal, but the addition of collagenase to the buffer resulted in a higher cumulative release of VEGF. Gelatin crosslinking extent was a significant factor on release from both microparticles alone and composite scaffolds in vitro and in vivo. VEGF bioactivity from composite scaffolds in vitro was maintained above 90% of the expected bioactivity over 14 days.

Conclusions

VEGF release kinetics were dependent on the extent of gelatin crosslinking and were characteristic of the specific growth factor due to the effects of growth factor size, charge, and conformation on its complexation with gelatin. These studies demonstrate the utility of gelatin microparticles and their composite scaffolds as delivery vehicles for the controlled release of VEGF for tissue engineering applications.

KEY WORDS

bone tissue engineering controlled drug delivery gelatin microparticles porous polymer scaffold vascular endothelial growth factor 

Abbreviations

bFGF

basic fibroblast growth factor

BMP-2

bone morphogenetic protein-2

Coll

collagenase-containing phosphate buffered saline

GPC

gel permeation chromatography

HUVECs

human umbilical vein endothelial cells

IGF-1

insulin-like growth factor-1

IEP

isoelectric point

microCT

microcomputed tomography

PBS

phosphate buffered saline

PPF

poly(propylene fumarate)

SEM

scanning electron microscopy

TGF-β1

transforming growth factor-β1

VEGF

vascular endothelial growth factor

VOI

volume of interest

Notes

Acknowledgments

The authors would like to acknowledge support of this work by a grant from the National Institutes of Health (R01-DE15164) (AGM) and by a National Science Foundation Graduate Research Fellowship (ZSP).

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Zarana S. Patel
    • 1
  • Hiroki Ueda
    • 2
  • Masaya Yamamoto
    • 2
  • Yasuhiko Tabata
    • 2
  • Antonios G. Mikos
    • 1
  1. 1.Department of BioengineeringRice UniversityHoustonUSA
  2. 2.Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical SciencesKyoto UniversityKyotoJapan

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