Citation
Tsui, J. H.; Janebodin, K.; Ieronimakis, N.; Yama, D. M. P.; Yang, H. S.; Chavanachat, R.; Hays, A. L.; Lee, H.; Reyes, M.; & Kim, D. H. (2017). Harnessing Sphingosine-1-Phosphate Signaling and Nanotopographical Cues To Regulate Skeletal Muscle Maturation and Vascularization. ACS Nano, 11(12), 11954-11968. PMCID: 6133580Abstract
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.Keyword(s)
*Nanotechnology*Signal TransductionAnimalsBiomimetic Materials/chemistry/metabolismCell DifferentiationCells, CulturedDose-Response Relationship, DrugEndothelial Cells/cytologyLysophospholipids/chemistry/*metabolismMiceMice, KnockoutMice, TransgenicMuscle, Skeletal/*blood supply/*metabolismNanoparticles/*chemistry/metabolismNeovascularization, Pathologic/*metabolismPolylactic Acid-Polyglycolic Acid Copolymer/chemistry/metabolismSphingosine/*analogs & derivatives/chemistry/metabolismNotes
Tsui, Jonathan HJanebodin, Kajohnkiart
Ieronimakis, Nicholas
Yama, David M P
Yang, Hee Seok
Chavanachat, Rakchanok
Hays, Aislinn L
Lee, Haeshin
Reyes, Morayma
Kim, Deok-Ho
P41 EB002027/EB/NIBIB NIH HHS/
R01 NS094388/NS/NINDS NIH HHS/
R21 AR064395/AR/NIAMS NIH HHS/
T32 AG000057/AG/NIA NIH HHS/
ACS Nano. 2017 Dec 26;11(12):11954-11968. doi: 10.1021/acsnano.7b00186. Epub 2017 Nov 28.
Reference Type
Journal ArticleSecondary Title
ACS NanoAuthor(s)
Tsui, J. H.Janebodin, K.Ieronimakis, N.Yama, D. M. P.Yang, H. S.Chavanachat, R.Hays, A. L.Lee, H.Reyes, M.Kim, D. H.Year Published
2017Date Published
1766707200Volume Number
11Issue Number
12Pages
11954-11968ISSN/ISBN
1936-086X (Electronic)1936-0851 (Linking)