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Controlled Release of IGF-1 and HGF from a Biodegradable Polyurethane Scaffold

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ABSTRACT

Purpose

Biodegradable elastomers, which can possess favorable mechanical properties and degradation rates for soft tissue engineering applications, are more recently being explored as depots for biomolecule delivery. The objective of this study was to synthesize and process biodegradable, elastomeric poly(ester urethane)urea (PEUU) scaffolds and to characterize their ability to incorporate and release bioactive insulin-like growth factor–1 (IGF-1) and hepatocyte growth factor (HGF).

Methods

Porous PEUU scaffolds made from either 5 or 8 wt% PEUU were prepared with direct growth-factor incorporation. Long-term in vitro IGF-1 release kinetics were investigated in saline or saline with 100 units/ml lipase to simulate in vivo degradation. Cellular assays were used to confirm released IGF-1 and HGF bioactivity.

Results

IGF-1 release into saline occurred in a complex multi-phasic manner for up to 440 days. Scaffolds generated from 5 wt% PEUU delivered protein faster than 8 wt% scaffolds. Lipase-accelerated scaffold degradation led to delivery of >90% protein over 9 weeks for both polymer concentrations. IGF-1 and HGF bioactivity in the first 3 weeks was confirmed.

Conclusions

The capacity of a biodegradable elastomeric scaffold to provide long-term growth-factor delivery was demonstrated. Such a system might provide functional benefit in cardiovascular and other soft tissue engineering applications.

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Abbreviations

BDI:

1,4-diisocyanatobutane

bFGF:

basic fibroblast growth factor

BSA:

bovine serum albumin

DMEM:

Dulbecco’s modified Eagle medium

DMSO:

dimethyl sulfoxide

HGF:

hepatocyte growth factor

HUVECs:

human umbilical vein endothelial cells

IGF-1:

insulin-like growth factor-1

MEM:

minimum essential medium

PBS:

phosphate-buffered saline

PCL:

polycaprolactone

PEUU:

poly(ester urethane)urea

TIPS:

thermally induced phase separation

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ACKNOWLEDGMENTS

This work was supported by the National Institutes of Health (NIH) grant #HL069368. Dr. Baraniak and Mr. Nelson were supported by NIH training grants #T32-EB001026-01 and #T32-HL076124, respectively.

Author information

Author notes

  1. Priya R. Baraniak

    Present address: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA

  2. Jianjun Guan

    Present address: Department of Materials Science and Engineering, The Ohio State University, Columbus, Ohio, USA

Authors and Affiliations

  1. Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Devin M. Nelson, Priya R. Baraniak & William R. Wagner

  2. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Devin M. Nelson, Priya R. Baraniak, Zuwei Ma, Jianjun Guan & William R. Wagner

  3. Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    N. Scott Mason

  4. Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    William R. Wagner

  5. McGowan Institute for Regenerative Medicine, 450 Technology Drive, Suite 300, Pittsburgh, Pennsylvania, 15219, USA

    William R. Wagner

Authors
  1. Devin M. Nelson
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  2. Priya R. Baraniak
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Corresponding author

Correspondence to William R. Wagner.

Additional information

Devin M. Nelson and Priya R. Baraniak contributed equally to this work.

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Nelson, D.M., Baraniak, P.R., Ma, Z. et al. Controlled Release of IGF-1 and HGF from a Biodegradable Polyurethane Scaffold. Pharm Res 28, 1282–1293 (2011). https://doi.org/10.1007/s11095-011-0391-z

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  • DOI: https://doi.org/10.1007/s11095-011-0391-z

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