Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels
Heparin-binding insulin-like growth factor 1 (HB-IGF-1) is a fusion protein of IGF-1 with the HB domain of heparin-binding epidermal growth factor-like growth factor. A single dose of HB-IGF-1 has been shown to bind specifically to cartilage and to promote sustained upregulation of proteoglycan synt...
| Main Authors: | , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Mary Ann Liebert, Inc.
2015
|
| Online Access: | http://hdl.handle.net/1721.1/95793 https://orcid.org/0000-0002-4942-3456 https://orcid.org/0000-0002-4121-8183 https://orcid.org/0000-0002-5770-838X |
| _version_ | 1826202549598814208 |
|---|---|
| author | Miller, Rachel Elizabeth Mroszczyk, Keri A. Lee, Richard T. Patwari, Parth Grodzinsky, Alan J. Florine, Emily Marie Liebesny, Paul Hancock |
| author2 | Lincoln Laboratory |
| author_facet | Lincoln Laboratory Miller, Rachel Elizabeth Mroszczyk, Keri A. Lee, Richard T. Patwari, Parth Grodzinsky, Alan J. Florine, Emily Marie Liebesny, Paul Hancock |
| author_sort | Miller, Rachel Elizabeth |
| collection | MIT |
| description | Heparin-binding insulin-like growth factor 1 (HB-IGF-1) is a fusion protein of IGF-1 with the HB domain of heparin-binding epidermal growth factor-like growth factor. A single dose of HB-IGF-1 has been shown to bind specifically to cartilage and to promote sustained upregulation of proteoglycan synthesis in cartilage explants. Achieving strong integration between native cartilage and tissue-engineered cartilage remains challenging. We hypothesize that if a growth factor delivered by the tissue engineering scaffold could stimulate enhanced matrix synthesis by both the cells within the scaffold and the adjacent native cartilage, integration could be enhanced. In this work, we investigated methods for adsorbing HB-IGF-1 to self-assembling peptide hydrogels to deliver the growth factor to encapsulated chondrocytes and cartilage explants cultured with growth factor-loaded hydrogels. We tested multiple methods for adsorbing HB-IGF-1 in self-assembling peptide hydrogels, including adsorption prior to peptide assembly, following peptide assembly, and with/without heparan sulfate (HS, a potential linker between peptide molecules and HB-IGF-1). We found that HB-IGF-1 and HS were retained in the peptide for all tested conditions. A subset of these conditions was then studied for their ability to stimulate increased matrix production by gel-encapsulated chondrocytes and by chondrocytes within adjacent native cartilage. Adsorbing HB-IGF-1 or IGF-1 prior to peptide assembly was found to stimulate increased sulfated glycosaminoglycan per DNA and hydroxyproline content of chondrocyte-seeded hydrogels compared with basal controls at day 10. Cartilage explants cultured adjacent to functionalized hydrogels had increased proteoglycan synthesis at day 10 when HB-IGF-1 was adsorbed, but not IGF-1. We conclude that delivery of HB-IGF-1 to focal defects in cartilage using self-assembling peptide hydrogels is a promising technique that could aid cartilage repair via enhanced matrix production and integration with native tissue. |
| first_indexed | 2024-09-23T12:09:15Z |
| format | Article |
| id | mit-1721.1/95793 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:09:15Z |
| publishDate | 2015 |
| publisher | Mary Ann Liebert, Inc. |
| record_format | dspace |
| spelling | mit-1721.1/957932022-10-01T08:31:35Z Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels Miller, Rachel Elizabeth Mroszczyk, Keri A. Lee, Richard T. Patwari, Parth Grodzinsky, Alan J. Florine, Emily Marie Liebesny, Paul Hancock Lincoln Laboratory Massachusetts Institute of Technology. Department of Biological Engineering Florine, Emily Marie Liebesny, Paul Hancock Mroszczyk, Keri A. Grodzinsky, Alan J. Heparin-binding insulin-like growth factor 1 (HB-IGF-1) is a fusion protein of IGF-1 with the HB domain of heparin-binding epidermal growth factor-like growth factor. A single dose of HB-IGF-1 has been shown to bind specifically to cartilage and to promote sustained upregulation of proteoglycan synthesis in cartilage explants. Achieving strong integration between native cartilage and tissue-engineered cartilage remains challenging. We hypothesize that if a growth factor delivered by the tissue engineering scaffold could stimulate enhanced matrix synthesis by both the cells within the scaffold and the adjacent native cartilage, integration could be enhanced. In this work, we investigated methods for adsorbing HB-IGF-1 to self-assembling peptide hydrogels to deliver the growth factor to encapsulated chondrocytes and cartilage explants cultured with growth factor-loaded hydrogels. We tested multiple methods for adsorbing HB-IGF-1 in self-assembling peptide hydrogels, including adsorption prior to peptide assembly, following peptide assembly, and with/without heparan sulfate (HS, a potential linker between peptide molecules and HB-IGF-1). We found that HB-IGF-1 and HS were retained in the peptide for all tested conditions. A subset of these conditions was then studied for their ability to stimulate increased matrix production by gel-encapsulated chondrocytes and by chondrocytes within adjacent native cartilage. Adsorbing HB-IGF-1 or IGF-1 prior to peptide assembly was found to stimulate increased sulfated glycosaminoglycan per DNA and hydroxyproline content of chondrocyte-seeded hydrogels compared with basal controls at day 10. Cartilage explants cultured adjacent to functionalized hydrogels had increased proteoglycan synthesis at day 10 when HB-IGF-1 was adsorbed, but not IGF-1. We conclude that delivery of HB-IGF-1 to focal defects in cartilage using self-assembling peptide hydrogels is a promising technique that could aid cartilage repair via enhanced matrix production and integration with native tissue. National Science Foundation (U.S.). Graduate Research Fellowship Program National Institutes of Health (U.S.) (Grant EB003805) National Institutes of Health (U.S.) (Grant AR060331) Whitaker Health Sciences Fund Fellowship Massachusetts Life Sciences Center Biomeasure, Inc. 2015-03-04T16:05:05Z 2015-03-04T16:05:05Z 2014-10 2013-11 Article http://purl.org/eprint/type/JournalArticle 1937-3341 1937-335X http://hdl.handle.net/1721.1/95793 Florine, Emily M., Rachel E. Miller, Paul H. Liebesny, Keri A. Mroszczyk, Richard T. Lee, Parth Patwari, and Alan J. Grodzinsky. “Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels.” Tissue Engineering Part A 21, no. 3–4 (February 2015): 637–646. © 2014 Mary Ann Liebert, Inc. https://orcid.org/0000-0002-4942-3456 https://orcid.org/0000-0002-4121-8183 https://orcid.org/0000-0002-5770-838X en_US http://dx.doi.org/10.1089/ten.TEA.2013.0679 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, Inc. Mary Ann Liebert |
| spellingShingle | Miller, Rachel Elizabeth Mroszczyk, Keri A. Lee, Richard T. Patwari, Parth Grodzinsky, Alan J. Florine, Emily Marie Liebesny, Paul Hancock Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels |
| title | Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels |
| title_full | Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels |
| title_fullStr | Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels |
| title_full_unstemmed | Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels |
| title_short | Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels |
| title_sort | delivering heparin binding insulin like growth factor 1 with self assembling peptide hydrogels |
| url | http://hdl.handle.net/1721.1/95793 https://orcid.org/0000-0002-4942-3456 https://orcid.org/0000-0002-4121-8183 https://orcid.org/0000-0002-5770-838X |
| work_keys_str_mv | AT millerrachelelizabeth deliveringheparinbindinginsulinlikegrowthfactor1withselfassemblingpeptidehydrogels AT mroszczykkeria deliveringheparinbindinginsulinlikegrowthfactor1withselfassemblingpeptidehydrogels AT leerichardt deliveringheparinbindinginsulinlikegrowthfactor1withselfassemblingpeptidehydrogels AT patwariparth deliveringheparinbindinginsulinlikegrowthfactor1withselfassemblingpeptidehydrogels AT grodzinskyalanj deliveringheparinbindinginsulinlikegrowthfactor1withselfassemblingpeptidehydrogels AT florineemilymarie deliveringheparinbindinginsulinlikegrowthfactor1withselfassemblingpeptidehydrogels AT liebesnypaulhancock deliveringheparinbindinginsulinlikegrowthfactor1withselfassemblingpeptidehydrogels |