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Author Notes:

Todd C. McDevitt, Ph.D., 315 Ferst Drive, Suite 2311, Atlanta GA, 30332-0532, Phone: 404-385-6647,Fax: 404-894-4243, todd.mcdevitt@bme.gatech.edu

The authors would like to thank Ms. Shalini Saxena for her assistance with scanning electron microscopy; and Ms. Marissa Cooke for her assistance with manuscript preparation.

Subject:

Research Funding:

This work was supported by a Transformative Research Award from the National Institutes of Health (TR01 AR062006); and a grant from the National Science Foundation (NSF DMR 1207045).

MHH is supported by funding from the Natural Science and Engineering Research Council (NSERC) of Canada.

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Materials Science, Biomaterials
  • Engineering
  • Materials Science
  • Heparin
  • Glycosaminoglycan
  • Bone morphogenetic protein
  • Microparticle
  • Alkaline phosphatase
  • Bone tissue engineering
  • FIBROBLAST-GROWTH-FACTOR
  • ACID-BASED HYDROGELS
  • OSTEOGENIC ACTIVITY
  • CONTROLLED-RELEASE
  • OSTEOBLAST DIFFERENTIATION
  • POLY(ETHYLENE GLYCOL)
  • EXTRACELLULAR-MATRIX
  • BIOMATERIAL CARRIERS
  • GELATIN MICROSPHERES
  • STEM-CELLS

Heparin microparticle effects on presentation and bioactivity of bone morphogenetic protein-2

Tools:

Journal Title:

Biomaterials

Volume:

Volume 35, Number 25

Publisher:

, Pages 7228-7238

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Biomaterials capable of providing localized and sustained presentation of bioactive proteins are critical for effective therapeutic growth factor delivery. However, current biomaterial delivery vehicles commonly suffer from limitations that can result in low retention of growth factors at the site of interest or adversely affect growth factor bioactivity. Heparin, a highly sulfated glycosaminoglycan, is an attractive growth factor delivery vehicle due to its ability to reversibly bind positively charged proteins, provide sustained delivery, and maintain protein bioactivity. This study describes the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. HMAm microparticles were shown to efficiently bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the maximum binding capacity of other common growth factor delivery vehicles, such as gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment, indicating that BMP-2-loaded microparticles retain bioactivity and potently elicit a functional cell response. In summary, our results suggest that heparin microparticles stably retain large amounts of bioactive BMP-2 for prolonged periods of time, and that presentation of BMP-2 via heparin microparticles can elicit cell responses comparable to soluble BMP-2 treatment. Consequently, heparin microparticles present an effective method of delivering and spatially retaining growth factors that could be used in a variety of systems to enable directed induction of cell fates and tissue regeneration.

Copyright information:

© 2014 Elsevier Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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