Engineering vascularized skeletal muscle tissue

Shulamit Levenberg, Jeroen Rouwkema, Mara Macdonald, Evan S. Garfein, Daniel S. Kohane, Diane C. Darland, Robert Marini, Clemens A. Van Blitterswijk, Richard C. Mulligan, Patricia A. D'Amore, Robert Langer

Research output: Contribution to journalArticle

893 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)879-884
Number of pages6
JournalNature biotechnology
Volume23
Issue number7
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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    Levenberg, S., Rouwkema, J., Macdonald, M., Garfein, E. S., Kohane, D. S., Darland, D. C., Marini, R., Van Blitterswijk, C. A., Mulligan, R. C., D'Amore, P. A., & Langer, R. (2005). Engineering vascularized skeletal muscle tissue. Nature biotechnology, 23(7), 879-884. https://doi.org/10.1038/nbt1109