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

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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.

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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

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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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Authors and Affiliations

  1. Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, Texas, 77251-1892, USA

    Zarana S. Patel & Antonios G. Mikos

  2. Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Hiroki Ueda, Masaya Yamamoto & Yasuhiko Tabata

Authors
  1. Zarana S. Patel
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  2. Hiroki Ueda
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  3. Masaya Yamamoto
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  4. Yasuhiko Tabata
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  5. Antonios G. Mikos
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Corresponding author

Correspondence to Antonios G. Mikos.

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Patel, Z.S., Ueda, H., Yamamoto, M. et al. In Vitro and In Vivo Release of Vascular Endothelial Growth Factor from Gelatin Microparticles and Biodegradable Composite Scaffolds. Pharm Res 25, 2370–2378 (2008). https://doi.org/10.1007/s11095-008-9685-1

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  • DOI: https://doi.org/10.1007/s11095-008-9685-1

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