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.

容量性肌肉丢失（VML）是导致功能严重且持续受损的骨骼肌丢失。与躯干和四肢骨骼肌相比，颅面肌的独特特征，包括基因表达，卫星细胞表型和再生能力的差异，提示VML损伤可能更严重地影响颅面肌。然而，尽管存在这些显着差异，但目前尚无颅面VML的动物模型。在先前的绵羊后肢VML研究中，我们证明了我们实验室的组织工程化骨骼肌单位（SMU）能够将肌肉力量的产生恢复到与未受伤的对侧肌肉在统计学上无法区分的水平。因此，本研究的目标是：1）在大型动物模型中开发颅面VML模型，以及2）评估我们的SMU修复绵羊肌主要肌肉中30％VML的功效。总体而言，SMU治疗组与未修复对照组之间的功能恢复无显着差异。尽管使用了我们先前研究中相同的损伤和修复模型，但结果显示颅面和后肢VML的病理生理差异。具体而言，颅面部模型受到后肢模型未表现出的同时去神经支配和缺血性损伤的影响。尽管在临床上很现实，但额外的局部缺血和神经支配可能造成了严重的损伤，以至于我们的SMU无法修复。这项研究强调了平衡使用临床现实模型的重要性，同时还要保持对与伤害严重性相关的变量的控制。这些变量包括肌肉切除量，VML损伤的位置以及损伤的几何形状，因为这些变量会影响肌肉的自我再生能力以及治疗成功的可能性。