Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)..
Biologically active ligands (e.g., RGDS from fibronectin) play critical roles in the development of chemically defined biomaterials. However, recent decades have shown only limited progress in discovering novel extracellular matrix-protein-derived ligands for translational applications. Through motif analysis of evolutionarily conserved RGD-containing regions in laminin (LM) and peptide-functionalized hydrogel microarray screening, we identified a peptide (a1) that showed superior supports for endothelial cell (EC) functions. Mechanistic studies attributed the results to the capacity of a1 engaging both LM- and Fn-binding integrins. RNA sequencing of ECs in a1-functionalized hydrogels showed ~60% similarities with Matrigel in "vasculature development" gene ontology terms. Vasculogenesis assays revealed the capacity of a1-formulated hydrogels to improve EC network formation. Injectable alginates functionalized with a1 and MMPQK (a vascular endothelial growth factor-mimetic peptide with a matrix metalloproteinase-degradable linker) increased blood perfusion and functional recovery over decellularized extracellular matrix and (RGDS + MMPQK)-functionalized hydrogels in an ischemic hindlimb model, illustrating the power of this approach.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Science advances - 6(2020), 28 vom: 01. Juli, Seite eaaz5894 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jia, Jia [VerfasserIn] |
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| Links: |
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| Themen: |
Hydrogels |
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| Anmerkungen: |
Date Completed 11.04.2022 Date Revised 27.09.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1126/sciadv.aaz5894 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Biologically active ligands (e.g., RGDS from fibronectin) play critical roles in the development of chemically defined biomaterials. However, recent decades have shown only limited progress in discovering novel extracellular matrix-protein-derived ligands for translational applications. Through motif analysis of evolutionarily conserved RGD-containing regions in laminin (LM) and peptide-functionalized hydrogel microarray screening, we identified a peptide (a1) that showed superior supports for endothelial cell (EC) functions. Mechanistic studies attributed the results to the capacity of a1 engaging both LM- and Fn-binding integrins. RNA sequencing of ECs in a1-functionalized hydrogels showed ~60% similarities with Matrigel in "vasculature development" gene ontology terms. Vasculogenesis assays revealed the capacity of a1-formulated hydrogels to improve EC network formation. Injectable alginates functionalized with a1 and MMPQK (a vascular endothelial growth factor-mimetic peptide with a matrix metalloproteinase-degradable linker) increased blood perfusion and functional recovery over decellularized extracellular matrix and (RGDS + MMPQK)-functionalized hydrogels in an ischemic hindlimb model, illustrating the power of this approach | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 7 | |a Hydrogels |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor A |2 NLM | |
| 700 | 1 | |a Jeon, Eun Je |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Richards, Dylan J |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Soojin |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Youngmee |e verfasserin |4 aut | |
| 700 | 1 | |a Barrs, Ryan W |e verfasserin |4 aut | |
| 700 | 1 | |a Coyle, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Chou, James C |e verfasserin |4 aut | |
| 700 | 1 | |a Yost, Michael J |e verfasserin |4 aut | |
| 700 | 1 | |a Gerecht, Sharon |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Seung-Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Mei, Ying |e verfasserin |4 aut | |
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