Engineered Skeletal Muscle Units for Repair of Volumetric Muscle Loss in the Tibialis Anterior Muscle of a Rat
Engineered Skeletal Muscle Units for Repair of Volumetric Muscle Loss in the Tibialis Anterior Muscle of a Rat
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DOI：
10.1089/ten.tea.2014.0060
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发表时间：
2014-11-01
影响因子：
4.1
通讯作者：
Larkin, Lisa M.
中科院分区：
文献类型：
--
作者：
VanDusen, Keith W.;Syverud, Brian C.;Larkin, Lisa M.
容积性肌肉丧失（VML）是肌肉组织的创伤性、退行性或手术性丧失，可能导致功能丧失和身体畸形。迄今为止，临床治疗VML-反射肌瓣或转移肌肉移植-是有限的组织可用性和供区发病率。为了满足对更创新的骨骼肌修复选择的需求，我们的实验室开发了无支架组织工程化骨骼肌单位（SMU），多相组织结构由工程化骨骼肌与工程化骨-肌腱末端，肌腱接头和附着点组成，在体外可以自发地和响应电刺激产生力。虽然在体外表型不成熟，我们已经表明，在异位部位植入1周后，我们的肌肉结构发展血管化和神经支配，外肌样结缔组织外层，肌球蛋白含量增加，肌纤维形成，并增加生产力。这些发现表明，我们的工程肌肉组织在植入后存活，并形成了将表型向成人肌肉推进所需的界面。本研究的目的是评估我们的SMU恢复急性VML部位肌肉组织的潜力。我们的研究结果表明，我们的SMU在体内继续成熟，恢复时间更长，并有可能通过为受损肌肉提供额外的肌纤维来修复VML部位。我们从这项研究中得出结论，我们的SMU有可能在急性VML病例中恢复丢失的组织体积。
Volumetric muscle loss (VML) is the traumatic, degenerative, or surgical loss of muscle tissue, which may result in function loss and physical deformity. To date, clinical treatments for VML-the reflected muscle flap or transferred muscle graft-are limited by tissue availability and donor site morbidity. To address the need for more innovative skeletal muscle repair options, our laboratory has developed scaffoldless tissue-engineered skeletal muscle units (SMUs), multiphasic tissue constructs composed of engineered skeletal muscle with engineered bone-tendon ends, myotendinous junctions, and entheses, which in vitro can produce force both spontaneously and in response to electrical stimulation. Though phenotypically immature in vitro, we have shown that following 1 week of implantation in an ectopic site, our muscle constructs develop vascularization and innervation, an epimysium-like outer layer of connective tissue, an increase in myosin protein content, formation of myofibers, and increased force production. These findings suggest that our engineered muscle tissue survives implantation and develops the interfaces necessary to advance the phenotype toward adult muscle. The purpose of this study was to evaluate the potential of our SMUs to restore muscle tissue to sites of acute VML. Our results indicate that our SMUs continue to mature in vivo with longer recovery times and have the potential to repair VML sites by providing additional muscle fibers to damaged muscles. We conclude from this study that our SMUs have the potential to restore lost tissue volume in cases of acute VML.