Jia, Jia Jeon, Eun Je Li, Mei Richards, Dylan J. Lee, Soojin Jung, Youngmee Barrs, Ryan W. Coyle, Robert Li, Xiaoyang Chou, James C. Yost, Michael J. Gerecht, Sharon Cho, Seung-Woo Mei, Ying 2024-01-19T17:04:23Z 2024-01-19T17:04:23Z 2021-09-05 2020-07 2375-2548 https://pubs.kist.re.kr/handle/201004/118453 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 (alpha 1) that showed superior supports for endothelial cell (EC) functions. Mechanistic studies attributed the results to the capacity of alpha 1 engaging both LM- and Fn-binding integrins. RNA sequencing of ECs in alpha 1-functionalized hydrogels showed similar to 60% similarities with Matrigel in "vasculature development" gene ontology terms. Vasculogenesis assays revealed the capacity of alpha 1-formulated hydrogels to improve EC network formation. Injectable alginates functionalized with alpha 1 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. English AMER ASSOC ADVANCEMENT SCIENCE CELL-BINDING SEQUENCES STEM-CELL EXTRACELLULAR-MATRIX ENDOTHELIAL-CELLS MOUSE LAMININ GLOBULAR DOMAIN PEPTIDE CHAIN IDENTIFICATION ANGIOGENESIS Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization Article 10.1126/sciadv.aaz5894 1 SCIENCE ADVANCES, v.6, no.28 SCIENCE ADVANCES 6 28 scie scopus 000548735600004 2-s2.0-85090051829 Multidisciplinary Sciences Science & Technology - Other Topics Article CELL-BINDING SEQUENCES STEM-CELL EXTRACELLULAR-MATRIX ENDOTHELIAL-CELLS MOUSE LAMININ GLOBULAR DOMAIN PEPTIDE CHAIN IDENTIFICATION ANGIOGENESIS