Department of Anesthesia and Medicine and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tissue Eng Part A. 2012 May;18(9-10):957-67. doi: 10.1089/ten.TEA.2011.0313. Epub 2012 Jan 4.
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.
骨骼肌组织工程领域目前受到缺乏形成由密集、对齐和成熟肌纤维组成的大型肌肉构建体的方法以及对发育中肌肉组织的结构-功能关系的有限理解的阻碍。在我们之前的研究中，通过在具有交错六边形柱的弹性组织模具内浇注细胞和纤维蛋白凝胶，制造出具有椭圆形孔的工程化肌肉薄片（“肌肉网络”）。在这些网络中，细胞围绕椭圆形孔的对齐遵循由纤维蛋白凝胶对六边形柱的细胞介导的压实产生的局部组织应变的分布。本研究的目的是评估孔伸长率的系统变化如何影响肌肉网络的形态和收缩功能。我们发现，在具有更长椭圆形孔的肌肉网络中，单个肌纤维的产生力没有改变，但是肌纤维的对齐和肌纤维形成的效率显著增加，尽管组织总体积减少，但总收缩力增加。超过一定的孔长度后，产生的收缩力的增加主要是由于更有效的肌纤维形成，而不是增强的肌纤维对齐。总的来说，这些研究表明，局部组织几何形状的变化可以对工程化肌肉的功能输出产生直接的结构和间接的肌源性影响。未来将探索不同的水凝胶配方和孔几何形状，以进一步增强工程化肌肉网络的收缩功能，并促进其在体外进行基本结构-功能研究，并最终促进体内有效的肌肉修复。
