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Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling

Author(s)
Kopesky, Paul Wayne; Vanderploeg, Eric J.; Kisiday, John D.; Frisbie, David D.; Grodzinsky, Alan J.
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Alternative title
Controlled Delivery of Transforming Growth Factor β1 [beta 1] by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling
Terms of use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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Abstract
Self-assembling peptide hydrogels were modified to deliver transforming growth factor b1 [beta 1](TGF-b1)[TGF beta 1] to encapsulated bone-marrow-derived stromal cells (BMSCs) for cartilage tissue engineering applications using two different approaches: (i) biotin-streptavidin tethering; (ii) adsorption to the peptide scaffold. Initial studies to determine the duration of TGF-b1 [TGF beta 1] medium supplementation necessary to stimulate chondrogenesis showed that 4 days of transient soluble TGF-b1 [TGF beta 1] to newborn bovine BMSCs resulted in 10-fold higher proteoglycan accumulation than TGF-b1-free [TGF beta 1 free]culture after 3 weeks. Subsequently, BMSC-seeded peptide hydrogels with either tethered TGF-b1 [TGF beta 1] (Teth-TGF) or adsorbed TGF-b1 [TGF beta 1] (Ads-TGF) were cultured in the TGF-b1-free [TGF beta 1 free] medium, and chondrogenesis was compared to that for BMSCs encapsulated in unmodified peptide hydrogels, both with and without soluble TGF-b1 [TGF beta 1] medium supplementation. Ads-TGF peptide hydrogels stimulated chondrogenesis of BMSCs as demonstrated by cell proliferation and cartilage-like extracellular matrix accumulation, whereas Teth- TGF did not stimulate chondrogenesis. In parallel experiments, TGF-b1 [TGF beta 1] adsorbed to agarose hydrogels stimulated comparable chondrogenesis. Full-length aggrecan was produced by BMSCs in response to Ads-TGF in both peptide and agarose hydrogels, whereas medium-delivered TGF-b1 [TGF beta 1] stimulated catabolic aggrecan cleavage product formation in agarose but not peptide scaffolds. Smad2/3 was transiently phosphorylated in response to Ads-TGF but not Teth-TGF, whereas medium-delivered TGF-b1 [TGF beta 1] produced sustained signaling, suggesting that dose and signal duration are potentially important for minimizing aggrecan cleavage product formation. Robustness of this technology for use in multiple species and ages was demonstrated by effective chondrogenic stimulation of adult equine BMSCs, an important translational model used before the initiation of human clinical studies.
Date issued
2010-09
URI
http://hdl.handle.net/1721.1/62026
Department
Massachusetts Institute of Technology. Center for Biomedical Engineering; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Journal
Tissue Engineering, Part A
Publisher
Mary Ann Liebert
Citation
Kopesky, Paul W. et al. “Controlled Delivery of Transforming Growth Factor Β1 [beta 1] by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling.” Tissue Engineering Part A 17.1-2 (2011) : 83-92. Copyright © 2011, Mary Ann Liebert, Inc.
Version: Final published version
ISSN
1937-3341
1937-335X

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