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Author Notes:

Corresponding author at: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA. Tel.: 1 404 332 5026; fax: 1 404 894 4243. johnna.temenoff@bme.gatech.edu (J.S. Temenoff).

We wish to acknowledge the core facilities at the Parker H. Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology for the use of their shared equipment, services, and expertise, as well as Liane Tellier for her assistance with polymer characterization.

Subjects:

Research Funding:

This study was supported with funding from the National Science Foundation (NSF) Graduate Research Fellowship (DGE-1148903) to TER, the Georgia Tech Petit Scholar Program to BDP, NSF (DMR 1207045), and National Institutes of Health Award Number R01AR062006.

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Materials Science, Biomaterials
  • Engineering
  • Materials Science
  • Heparin
  • Microparticles
  • Cell differentiation
  • Protein sequestration
  • IGFBP
  • MESENCHYMAL STEM-CELLS
  • GROWTH-FACTOR-I
  • HEPARAN-SULFATE
  • CONTROLLED-RELEASE
  • AFFINITY BINDING
  • ORGAN-CULTURE
  • HYDROGELS
  • BIOMATERIALS
  • DELIVERY
  • CHONDROGENESIS

Microparticle-mediated sequestration of cell-secreted proteins to modulate chondrocytic differentiation

Tools:

Journal Title:

Acta Biomaterialia

Volume:

Volume 68

Publisher:

, Pages 125-136

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Protein delivery is often used in tissue engineering applications to control differentiation processes, but is limited by protein instability and cost. An alternative approach is to control the cellular microenvironment through biomaterial-mediated sequestration of cell-secreted proteins important to differentiation. Thus, we utilized heparin-based microparticles to modulate cellular differentiation via protein sequestration in an in vitro model system of endochondral ossification. Heparin and poly(ethylene-glycol) (PEG; a low-binding material control)-based microparticles were incorporated into ATDC5 cell spheroids or incubated with ATDC5 cells in transwell culture. Reduced differentiation was observed in the heparin microparticle group as compared to PEG and no microparticle-containing groups. To determine if observed changes were due to sequestration of cell-secreted protein, the proteins sequestered by heparin microparticles were analyzed using SDS-PAGE and mass spectrometry. It was found that heparin microparticles bound insulin-like growth factor binding proteins (IGFBP)-3 and 5. When incubated with a small-molecule inhibitor of IGFBPs, NBI 31772, a similar delay in differentiation of ATDC5 cells was observed. These results indicate that heparin microparticles modulated chondrocytic differentiation in this system via sequestration of cell-secreted protein, a technique that could be beneficial in the future as a means to control cellular differentiation processes. Statement of Significance: In this work, we present a proof-of-principle set of experiments in which heparin-based microparticles are shown to modulate cellular differentiation through binding of cell-secreted protein. Unlike existing systems that rely on expensive protein with limited half-lives to elicit changes in cellular behavior, this technique focuses on temporal modulation of cell-generated proteins. This technique also provides a biomaterials-based method that can be used to further identify sequestered proteins of interest. Thus, this work indicates that glycosaminoglycan-based biomaterial approaches could be used as substitutes or additions to traditional methods for modulating and identifying the cell-secreted proteins involved in directing cellular behavior.

Copyright information:

© 2018 Acta Materialia Inc.

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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