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  4. Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling
 
research article

Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling

Guc, Esra
•
Briquez, Priscilla S.
•
Foretay, Didier
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2017
Biomaterials

Lymphangiogenesis occurs in inflammation and wound healing, yet its functional roles in these processes are not fully understood. Consequently, clinically relevant strategies for therapeutic lymphangiogenesis remain underdeveloped, particularly using growth factors. To achieve controlled, local capillary lymphangiogenesis with protein engineering and determine its effects on fluid clearance, leukocyte trafficking, and wound healing, we developed a fibrin-binding variant of vascular endothelial growth factor C (FB-VEGF-C) that is slowly released upon demand from infiltrating cells. Using a novel wound healing model, we show that implanted fibrin containing FB-VEGF-C, but not free VEGF-C, could stimulate local lymphangiogenesis in a dose-dependent manner. Importantly, the effects of FB-VEGF-C were restricted to lymphatic capillaries, with no apparent changes to blood vessels and downstream collecting vessels. Leukocyte intravasation and trafficking to lymph nodes were increased in hyperplastic lymphatics, while fluid clearance was maintained at physiological levels. In diabetic wounds, FB-VEGF-C-induced lymphangiogenesis increased extracellular matrix deposition and granulation tissue thickening, indicators of improved wound healing. Together, these results indicate that FB-VEGF-C is a promising strategy for inducing lymphangiogenesis locally, and that such lymphangiogenesis can promote wound healing by enhancing leukocyte trafficking without affecting downstream lymphatic collecting vessels. (C) 2017 The Authors. Published by Elsevier Ltd.

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Type
research article
DOI
10.1016/j.biomaterials.2017.03.033
Web of Science ID

WOS:000401393600014

Author(s)
Guc, Esra
Briquez, Priscilla S.
Foretay, Didier
Fankhauser, Manuel A.
Hubbell, Jeffrey A.  
Kilarski, Witold W.
Swartz, Melody A.  
Date Issued

2017

Published in
Biomaterials
Volume

131

Start page

160

End page

175

Subjects

VEGF-C

•

Fibrin

•

Lymphatics

•

Regenerative medicine

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LMRP  
LLCB  
Available on Infoscience
July 10, 2017
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/138947
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