Local Tissue Geometry Determines Contractile Force Generation of Engineered Muscle Networks

作     者：Bian, Weining Juhas, Mark Pfeiler, Terry W. Bursac, Nenad 

作者机构：Duke Univ Dept Biomed Engn Durham NC 27708 USA Harvard Univ Brigham & Womens Hosp Sch Med Dept Anesthesia & Med Boston MA 02115 USA Harvard Univ Brigham & Womens Hosp Sch Med Cardiovasc Div Boston MA 02115 USA 

出 版 物：《TISSUE ENGINEERING PART A》 (Tissue Eng. Part A)

年 卷 期：2012年第18卷第9-10期

页      面：957-967页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 

基　　金：Center for Biomolecular and Tissue Engineering at Duke University NIH from National Institute of Arthritis and Musculoskeletal and Skin Disease [AR055226] 

主　　题：muscles Structure-function relationships Pore Alignment Skeletal muscle Network 

摘      要：The field of skeletal muscle tissue engineering is currently hampered by the lack of methods to form large muscle constructs composed of dense, aligned, and mature myofibers and limited understanding of structure-function relationships in developing muscle tissues. In our previous studies, engineered muscle sheets with elliptical pores (muscle networks ) were fabricated by casting cells and fibrin gel inside elastomeric tissue molds with staggered hexagonal posts. In these networks, alignment of cells around the elliptical pores followed the local distribution of tissue strains that were generated by cell-mediated compaction of fibrin gel against the hexagonal posts. The goal of this study was to assess how systematic variations in pore elongation affect the morphology and contractile function of muscle networks. We found that in muscle networks with more elongated pores the force production of individual myofibers was not altered, but the myofiber alignment and efficiency of myofiber formation were significantly increased yielding an increase in the total contractile force despite a decrease in the total tissue volume. Beyond a certain pore length, increase in generated contractile force was mainly contributed by more efficient myofiber formation rather than enhanced myofiber alignment. Collectively, these studies show that changes in local tissue geometry can exert both direct structural and indirect myogenic effects on the functional output of engineered muscle. Different hydrogel formulations and pore geometries will be explored in the future to further augment contractile function of engineered muscle networks and promote their use for basic structure-function studies in vitro and, eventually, for efficient muscle repair in vivo.