Engineering vascularized skeletal muscle tissue.
One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.
Levenberg
Shulamit
S
Department of Biomedical Engineering, Technion 32000, Haifa, Israel. shulamit@bm.technion.ac.il
Rouwkema
Jeroen
J
Macdonald
Mara
M
Garfein
Evan S
ES
Kohane
Daniel S
DS
Darland
Diane C
DC
Marini
Robert
R
van Blitterswijk
Clemens A
CA
Mulligan
Richard C
RC
D'Amore
Patricia A
PA
Langer
Robert
R
D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000166:cytology; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply*; D032448:Myoblasts, Skeletal / Q000502:physiology; D018919:Neovascularization, Physiologic; D023822:Tissue Engineering / Q000379:methods*