Engineering vascularized skeletal muscle tissue

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.

Prospectus of cultured meat—advancing meat alternatives

“…Another method of increasing medium perfusion is by vascularizing the tissue being grown. Levenberg et al (2005) had induced endothelial vessel networks in skeletal muscle tissue constructs by using a co-culture of myoblasts, embryonic fibroblasts and endothelial cells co-seeded onto a highly porous biodegradable scaffold. Research size rotating bioreactors have been scaled up to three liters and, theoretically, scale up to industrial sizes should not affect the physics of the system.…”

Endothelialization of Acellular Porcine ECM with Chemical Modification

“…The successful regeneration of thick tissue like cardiac left ventricles has been greatly hampered by the lack of vascularization [4], [5]. Cardiac tissue possesses a complicated and hierarchical network of blood vessels.…”

VEGF Improves Skeletal Muscle Regeneration After Acute Trauma and Reconstruction of the Limb in a Rabbit Model

“…After experimental muscle damage, VEGF and its receptors are expressed in regenerating muscle fibers, suggesting there is an autocrine pathway that may promote survival and regeneration of myocytes [23]. Levenberg et al [17] reported a direct effect of VEGF-engineered myoblasts transplanted subcutaneously into nude mice. The transplantation led to substantially more muscle mass and higher neovascularization.…”

“…The average weight of the animals was 3.8 kg. Data from these same animals were reported to explore the effects on callus [17]. To highlight the effect of VEGF on two different tissues (muscle and bone) and to emphasize different potential therapeutic strategies, we thought it was necessary to publish these results separately.…”