title: Nanopatterned muscle cell patches for enhanced myogenesis and dystrophin expression in a mouse model of muscular dystrophy.
abstract: Skeletal muscle is a highly organized tissue in which the extracellular matrix (ECM) is composed of highly-aligned cables of collagen with nanoscale feature sizes, and provides structural and functional support to muscle fibers. As such, the transplantation of disorganized tissues or the direct injection of cells into muscles for regenerative therapy often results in suboptimal functional improvement due to a failure to integrate with native tissue properly. Here, we present a simple method in which biodegradable, biomimetic substrates with precisely controlled nanotopography were fabricated using solvent-assisted capillary force lithography (CFL) and were able to induce the proper development and differentiation of primary mononucleated cells to form mature muscle patches. Cells cultured on these nanopatterned substrates were highly-aligned and elongated, and formed more mature myotubes as evidenced by up-regulated expression of the myogenic regulatory factors Myf5, MyoD and myogenin (MyoG). When transplanted into mdx mice models for Duchenne muscular dystrophy (DMD), the proposed muscle patches led to the formation of a significantly greater number of dystrophin-positive muscle fibers, indicating that dystrophin replacement and myogenesis is achievable in vivo with this approach. These results demonstrate the feasibility of utilizing biomimetic substrates not only as platforms for studying the influences of the ECM on skeletal muscle function and maturation, but also to create transplantable muscle cell patches for the treatment of chronic and acute muscle diseases or injuries.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, South Korea.
authors.forename: Hee Seok
authors.initials: HS
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA; Department of Laboratory Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ieronimakis
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Tsui
authors.affiliation: School of Mechanical and Aerospace Engineering and the Institute of Bioengineering, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Hong Nam
authors.initials: HN
authors.lastname: Kim
authors.affiliation: School of Mechanical and Aerospace Engineering and the Institute of Bioengineering, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Kahp-Yang
authors.initials: KY
authors.lastname: Suh
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA; Department of Laboratory Medicine, University of Washington, Seattle, WA 98109, USA. Electronic address: morayma@uw.edu.
authors.forename: Morayma
authors.initials: M
authors.lastname: Reyes
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA. Electronic address: deokho@uw.edu.
authors.forename: Deok-Ho
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D051379:Mice; D018625:Microscopy, Atomic Force; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000473:pathology*; D036103:Nanotechnology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016189:Dystrophin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Muscle tissue engineering; Muscular dystrophy; Myogenesis; Nanotopography; Poly(lactic-co-glycolic acid)