TY - JOUR
T1 - Harnessing Sphingosine-1-Phosphate Signaling and Nanotopographical Cues to Regulate Skeletal Muscle Maturation and Vascularization
AU - Tsui, Jonathan H.
AU - Janebodin, Kajohnkiart
AU - Ieronimakis, Nicholas
AU - Yama, David M.P.
AU - Yang, Hee Seok
AU - Chavanachat, Rakchanok
AU - Hays, Aislinn L.
AU - Lee, Haeshin
AU - Reyes, Morayma
AU - Kim, Deok Ho
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/12/26
Y1 - 2017/12/26
N2 - Despite possessing substantial regenerative capacity, skeletal muscle can suffer from loss of function due to catastrophic traumatic injury or degenerative disease. In such cases, engineered tissue grafts hold the potential to restore function and improve patient quality of life. Requirements for successful integration of engineered tissue grafts with the host musculature include cell alignment that mimics host tissue architecture and directional functionality, as well as vascularization to ensure tissue survival. Here, we have developed biomimetic nanopatterned poly(lactic-co-glycolic acid) substrates conjugated with sphingosine-1-phosphate (S1P), a potent angiogenic and myogenic factor, to enhance myoblast and endothelial maturation. Primary muscle cells cultured on these functionalized S1P nanopatterned substrates developed a highly aligned and elongated morphology and exhibited higher expression levels of myosin heavy chain, in addition to genes characteristic of mature skeletal muscle. We also found that S1P enhanced angiogenic potential in these cultures, as evidenced by elevated expression of endothelial-related genes. Computational analyses of live-cell videos showed a significantly improved functionality of tissues cultured on S1P-functionalized nanopatterns as indicated by greater myotube contraction displacements and velocities. In summary, our study demonstrates that biomimetic nanotopography and S1P can be combined to synergistically regulate the maturation and vascularization of engineered skeletal muscles.
AB - Despite possessing substantial regenerative capacity, skeletal muscle can suffer from loss of function due to catastrophic traumatic injury or degenerative disease. In such cases, engineered tissue grafts hold the potential to restore function and improve patient quality of life. Requirements for successful integration of engineered tissue grafts with the host musculature include cell alignment that mimics host tissue architecture and directional functionality, as well as vascularization to ensure tissue survival. Here, we have developed biomimetic nanopatterned poly(lactic-co-glycolic acid) substrates conjugated with sphingosine-1-phosphate (S1P), a potent angiogenic and myogenic factor, to enhance myoblast and endothelial maturation. Primary muscle cells cultured on these functionalized S1P nanopatterned substrates developed a highly aligned and elongated morphology and exhibited higher expression levels of myosin heavy chain, in addition to genes characteristic of mature skeletal muscle. We also found that S1P enhanced angiogenic potential in these cultures, as evidenced by elevated expression of endothelial-related genes. Computational analyses of live-cell videos showed a significantly improved functionality of tissues cultured on S1P-functionalized nanopatterns as indicated by greater myotube contraction displacements and velocities. In summary, our study demonstrates that biomimetic nanotopography and S1P can be combined to synergistically regulate the maturation and vascularization of engineered skeletal muscles.
KW - nanotopography
KW - skeletal muscle
KW - sphingosine-1-phosphate
KW - tissue engineering
KW - vascularization
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U2 - 10.1021/acsnano.7b00186
DO - 10.1021/acsnano.7b00186
M3 - Article
C2 - 29156133
AN - SCOPUS:85040052621
SN - 1936-0851
VL - 11
SP - 11954
EP - 11968
JO - ACS Nano
JF - ACS Nano
IS - 12
ER -