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Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization
- Source :
- Science Advances
- Publication Year :
- 2020
- Publisher :
- American Association for the Advancement of Science (AAAS), 2020.
-
Abstract
- Motif analysis on evolutionarily conserved regions in laminin enabled the discovery of novel ligands for hydrogel development.<br />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.
- Subjects :
- Vascular Endothelial Growth Factor A
Materials Science
Integrin
Ligands
complex mixtures
Extracellular matrix
Vasculogenesis
Laminin
Extracellular
Animals
Research Articles
Conserved Sequence
Matrigel
Multidisciplinary
biology
Chemistry
technology, industry, and agriculture
SciAdv r-articles
Life Sciences
Hydrogels
Extracellular Matrix
Cell biology
Fibronectin
Self-healing hydrogels
biology.protein
Peptides
Research Article
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Science Advances
- Accession number :
- edsair.doi.dedup.....286559b2593ee8fd4c288bf2df8efbed