Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2020 Sep 21;15(9):e0239152. doi: 10.1371/journal.pone.0239152. eCollection 2020.
Volumetric muscle loss (VML) is the loss of skeletal muscle that results in significant and persistent impairment of function. The unique characteristics of craniofacial muscle compared trunk and limb skeletal muscle, including differences in gene expression, satellite cell phenotype, and regenerative capacity, suggest that VML injuries may affect craniofacial muscle more severely. However, despite these notable differences, there are currently no animal models of craniofacial VML. In a previous sheep hindlimb VML study, we showed that our lab's tissue engineered skeletal muscle units (SMUs) were able to restore muscle force production to a level that was statistically indistinguishable from the uninjured contralateral muscle. Thus, the goals of this study were to: 1) develop a model of craniofacial VML in a large animal model and 2) to evaluate the efficacy of our SMUs in repairing a 30% VML in the ovine zygomaticus major muscle. Overall, there was no significant difference in functional recovery between the SMU-treated group and the unrepaired control. Despite the use of the same injury and repair model used in our previous study, results showed differences in pathophysiology between craniofacial and hindlimb VML. Specifically, the craniofacial model was affected by concomitant denervation and ischemia injuries that were not exhibited in the hindlimb model. While clinically realistic, the additional ischemia and denervation likely created an injury that was too severe for our SMUs to repair. This study highlights the importance of balancing the use of a clinically realistic model while also maintaining control over variables related to the severity of the injury. These variables include the volume of muscle removed, the location of the VML injury, and the geometry of the injury, as these affect both the muscle's ability to self-regenerate as well as the probability of success of the treatment.
体积性肌肉损失（VML）是指骨骼肌的损失，导致功能显著和持续受损。颅面肌肉与躯干和四肢骨骼肌肉具有独特的特征，包括基因表达、卫星细胞表型和再生能力的差异，这表明 VML 损伤可能对面部肌肉的影响更为严重。然而，尽管存在这些显著差异，但目前还没有颅面 VML 的动物模型。在之前的绵羊后肢 VML 研究中，我们表明，我们实验室的组织工程化骨骼肌单元（SMU）能够恢复肌肉力量产生，使其达到与未受伤对侧肌肉在统计学上无法区分的水平。因此，本研究的目的是：1）在大型动物模型中建立颅面 VML 模型，2）评估我们的 SMU 修复绵羊颧大肌 30% VML 的效果。总体而言，SMU 治疗组和未修复对照组在功能恢复方面没有显著差异。尽管使用了与我们之前研究相同的损伤和修复模型，但结果表明颅面和后肢 VML 之间存在病理生理学差异。具体来说，颅面模型受到了同时发生的去神经和缺血性损伤的影响，而这些损伤在后肢模型中没有表现出来。尽管具有临床现实性，但额外的缺血和去神经损伤可能导致损伤过于严重，我们的 SMU 无法修复。本研究强调了在平衡使用临床现实模型的同时，保持对与损伤严重程度相关的变量的控制的重要性。这些变量包括去除的肌肉量、VML 损伤的位置和损伤的几何形状，因为这些因素会影响肌肉自我再生的能力以及治疗成功的概率。
