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Tuning of Collagen Scaffold Properties Modulates Embedded Endothelial Cell Regulatory Phenotype in Repair of Vascular Injuries In Vivo
Author(s) -
Unterman Shimon,
Freiman Alina,
Beckerman Margarita,
Abraham Eytan,
Stanley James R. L.,
Levy Ela,
Artzi Natalie,
Edelman Elazer
Publication year - 2015
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201500457
Subject(s) - in vivo , microbiology and biotechnology , scaffold , viability assay , inflammation , matrix metalloproteinase , endothelial stem cell , vascular smooth muscle , cell , intimal hyperplasia , chemistry , in vitro , biology , immunology , biomedical engineering , medicine , biochemistry , endocrinology , smooth muscle
Perivascularly implanted matrix embedded endothelial cells (MEECs) are potent regulators of inflammation and intimal hyperplasia following vascular injuries. Endothelial cells (ECs) in collagen scaffolds adopt a reparative phenotype with significant therapeutic potential. Although the biology of MEECs is increasingly understood, tuning of scaffold properties to control cell–substrate interactions is less well‐studied. It is hypothesized that modulating scaffold degradation would change EC phenotype. Scaffolds with differential degradation are prepared by cross‐linking and predegradation. Vascular injury increases degradation and the presence of MEECs retards injury‐mediated degradation. MEECs respond to differential scaffold properties with altered viability in vivo, suppressed smooth muscle cell (SMC) proliferation in vitro, and altered interleukin‐6 and matrix metalloproteinase‐9 expression. When implanted perivascularly to a murine carotid wire injury, tuned scaffolds change MEEC effects on vascular repair and inflammation. Live animal imaging enables real‐time tracking of cell viability, inflammation, and scaffold degradation, affording an unprecedented understanding of interactions between cells, substrate, and tissue. MEEC‐treated injuries improve endothelialization and reduce SMC hyperplasia over 14 d. These data demonstrate the potent role material design plays in tuning MEEC efficacy in vivo, with implications for the design of clinical therapies.