한빛사 논문
Jia Jia1,2,*, Eun Je Jeon3,4,*, Mei Li1,5, Dylan J. Richards1,2,†, Soojin Lee6,7, Youngmee Jung7,8, Ryan W. Barrs1,2, Robert Coyle1,2, Xiaoyang Li9,10, James C. Chou9, Michael J. Yost11, Sharon Gerecht12, Seung-Woo Cho3,13,14,‡ and Ying Mei1,2,‡
1Bioengineering Department, Clemson University, Clemson, SC, USA.
2Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.
3Department of Biotechnology, Yonsei University, Seoul, Republic of Korea.
4Department of Biomaterials Science and Engineering, Yonsei University, Seoul, Republic of Korea.
5Department of Cardiology, Medical University of South Carolina, Charleston, SC, USA.
6Program in Nanoscience and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
7Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, Republic of Korea.
8Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, Republic of Korea.
9Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, SC, USA.
10Ocean University of China, School of Medicine and Pharmacy, Qingdao, Shandong, China.
11Department of Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
12Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology, and Johns Hopkins Physical Sciences–Oncology Center, The Johns Hopkins University, Baltimore, MD, USA.
13Center for Nanomedicine, Institute for Basic Science (IBS), Seoul, Republic of Korea.
14Graduate Program of Nano Biomedical Engineering (NanoBME), Advanced Science Institute, Yonsei University, Seoul, Republic of Korea.
‡Corresponding author.
*These authors contributed equally to this work.
†Present address: Immunology Translational Science, Janssen Research and Development, LLC, Spring House, PA, USA.
Abstract
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.
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