Matrix mechanical properties modulate ECFC vascular network formation
Abstract
Development of a functional vascular network is a major problem limiting current tissue engineering strategies targeting repair and regeneration of damaged or diseased tissue. Recently endothelial colony forming cells (ECFCs) have been shown to vascularize a type I collagen scaffold in vivo. ECFCs are the only cells that have been shown to possess direct in vivo vessel forming ability upon transplantation. This has generated much interest in the use of ECFCs for tissue engineering strategies. However, there is still a great need for refinement of a defined microenvironment to locally deliver ECFCs and guide vessel formation in vivo. By regulating cross link formation, a novel mechanism to alter the matrix microenvironment and influence endothelial cell behavior, type I collagen scaffolds can potentially be engineered to support the formation of long lasting ECFC derived vessels. We investigated how collagen matrix microenvironment and physical parameters (matrix stiffness, fibril density, and collagen cross link composition) affected vascular network formation by ECFCs in vitro. Further we have characterized how collagen matrix design parameters modulate a matrix-integrin-cytoskeleton signaling axis known to regulate endothelial cell lumen formation. The results from this study will provide critical information for the development of vascularized tissue constructs that can be controllably delivered to ischemic areas and improve the efficacy of human umbilical cord blood derived ECFC therapies for human subjects.
Degree
Ph.D.
Advisors
Voytik-Harbin, Purdue University.
Subject Area
Biomedical engineering
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