Vega-Soto Emmanuel E, Rodriguez Brittany L, Armstrong Rachel E, Larkin Lisa M
Department of Molecular & Integrative Physiology, 2025 BSRB 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200.
Department of Biomedical Engineering University of Michigan, 2025 BSRB 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200.
Regen Eng Transl Med. 2020 Mar;6(1):62-68. doi: 10.1007/s40883-019-00117-2. Epub 2019 Jul 16.
Volumetric muscle loss (VML) is defined as the loss of skeletal muscle tissue which exceeds the body's repair capabilities leading to sustained functional deficits over time. Some etiologies leading to VML include traumatic injuries, congenital diseases, and degenerative myopathies. Currently, the lack of standardized animal models prevents an appropriate estimation of the severity of injury capable of exceeding self-regeneration. Recent work in our laboratory has shown that a 30% VML does not create a sustained functional loss in rats after 3 months. Therefore, the purpose of this study was to evaluate the percentage threshold of muscle loss that results in permanent functional deficits. We surgically created models of 30, 40, and 50% VML injuries in the tibialis anterior (TA) of rats, and subsequently evaluated TA function and structure after a 90-day recovery period. TA muscle force production was measured by stimulating the sciatic nerve to obtain a maximum tetanic force. Results revealed that the maximum force produced by rats with a 30% VML was not significantly different from the uninjured muscle, while the maximum force of the 40% and 50% VML groups was significantly lower in comparison to the uninjured muscle. Overall, this study further supports our observations, suggesting that a 30% VML rat model is not suitable for VML studies. Thus, increasing VML percentages might provide an improved standardized and clinically relevant model for VML that produces a long-term deficit in muscle self-regeneration, while providing a strong base for future tissue engineering techniques in medicine.
容积性肌肉损失(VML)被定义为骨骼肌组织的损失,这种损失超过了身体的修复能力,随着时间的推移会导致持续的功能缺陷。导致VML的一些病因包括创伤性损伤、先天性疾病和退行性肌病。目前,缺乏标准化的动物模型妨碍了对能够超过自我再生能力的损伤严重程度进行适当评估。我们实验室最近的研究表明,30%的VML在3个月后不会在大鼠身上造成持续的功能损失。因此,本研究的目的是评估导致永久性功能缺陷的肌肉损失百分比阈值。我们通过手术在大鼠的胫骨前肌(TA)上创建了30%、40%和50%VML损伤的模型,随后在90天的恢复期后评估TA的功能和结构。通过刺激坐骨神经以获得最大强直收缩力来测量TA肌肉的力量产生。结果显示,30%VML的大鼠产生的最大力量与未受伤肌肉没有显著差异,而40%和50%VML组的最大力量与未受伤肌肉相比显著更低。总体而言,本研究进一步支持了我们的观察结果,表明30%VML大鼠模型不适用于VML研究。因此,增加VML的百分比可能会提供一个改进的、标准化的且与临床相关的VML模型,该模型会导致肌肉自我再生出现长期缺陷,同时为未来医学中的组织工程技术提供坚实基础。