Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling
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) adso...
| Main Authors: | , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Mary Ann Liebert
2011
|
| Online Access: | http://hdl.handle.net/1721.1/62026 https://orcid.org/0000-0003-0026-6215 https://orcid.org/0000-0002-4942-3456 |
| _version_ | 1811097822607441920 |
|---|---|
| author | Kopesky, Paul Wayne Vanderploeg, Eric J. Kisiday, John D. Frisbie, David D. Grodzinsky, Alan J. |
| author2 | Massachusetts Institute of Technology. Center for Biomedical Engineering |
| author_facet | Massachusetts Institute of Technology. Center for Biomedical Engineering Kopesky, Paul Wayne Vanderploeg, Eric J. Kisiday, John D. Frisbie, David D. Grodzinsky, Alan J. |
| author_sort | Kopesky, Paul Wayne |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:05:30Z |
| format | Article |
| id | mit-1721.1/62026 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:05:30Z |
| publishDate | 2011 |
| publisher | Mary Ann Liebert |
| record_format | dspace |
| spelling | mit-1721.1/620262022-09-29T23:37:11Z Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling 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 Kopesky, Paul Wayne Vanderploeg, Eric J. Kisiday, John D. Frisbie, David D. Grodzinsky, Alan J. 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 Grodzinsky, Alan J. Kopesky, Paul Wayne Vanderploeg, Eric J. Grodzinsky, Alan J. 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. National Institutes of Health (U.S.) ( (NIH EB003805) (NIH AR33236) (NIH AR45779) National Institutes of Health (U.S.). Molecular, Cell, and Tissue Biomechanics Training Grant Fellowship Arthritis Foundation 2011-04-01T22:33:16Z 2011-04-01T22:33:16Z 2010-09 2010-03 Article http://purl.org/eprint/type/JournalArticle 1937-3341 1937-335X http://hdl.handle.net/1721.1/62026 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. https://orcid.org/0000-0003-0026-6215 https://orcid.org/0000-0002-4942-3456 en_US http://dx.doi.org/10.1089/ten.TEA.2010.0198 Tissue Engineering, Part A 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. application/pdf Mary Ann Liebert Mary Ann Liebert |
| spellingShingle | Kopesky, Paul Wayne Vanderploeg, Eric J. Kisiday, John D. Frisbie, David D. Grodzinsky, Alan J. Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling |
| title | Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling |
| title_full | Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling |
| title_fullStr | Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling |
| title_full_unstemmed | Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling |
| title_short | Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling |
| title_sort | controlled delivery of transforming growth factor β1 by self assembling peptide hydrogels induces chondrogenesis of bone marrow stromal cells and modulates smad2 3 signaling |
| url | http://hdl.handle.net/1721.1/62026 https://orcid.org/0000-0003-0026-6215 https://orcid.org/0000-0002-4942-3456 |
| work_keys_str_mv | AT kopeskypaulwayne controlleddeliveryoftransforminggrowthfactorb1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling AT vanderploegericj controlleddeliveryoftransforminggrowthfactorb1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling AT kisidayjohnd controlleddeliveryoftransforminggrowthfactorb1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling AT frisbiedavidd controlleddeliveryoftransforminggrowthfactorb1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling AT grodzinskyalanj controlleddeliveryoftransforminggrowthfactorb1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling AT kopeskypaulwayne controlleddeliveryoftransforminggrowthfactorb1beta1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling AT vanderploegericj controlleddeliveryoftransforminggrowthfactorb1beta1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling AT kisidayjohnd controlleddeliveryoftransforminggrowthfactorb1beta1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling AT frisbiedavidd controlleddeliveryoftransforminggrowthfactorb1beta1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling AT grodzinskyalanj controlleddeliveryoftransforminggrowthfactorb1beta1byselfassemblingpeptidehydrogelsinduceschondrogenesisofbonemarrowstromalcellsandmodulatessmad23signaling |