Biomedical Engineering, University of Virginia, Charlottesville, VA, United States.
Biomedical Engineering, University of Virginia, Charlottesville, VA, United States; Orthopaedic Surgery, University of Virginia, Charlottesville, VA, United States.
J Biomech. 2019 Mar 6;85:118-125. doi: 10.1016/j.jbiomech.2019.01.025. Epub 2019 Jan 19.
Volumetric muscle loss injuries (VML) are challenging to treat because of the variability in wound location. Regenerative medicine offers promising alternative treatments, but there is little understanding of the correlation between magnitude of VML injuries and corresponding functional deficits that must be addressed. There is a need for a tool that can elucidate the relationship between VML injury and force loss, as well as the impact on specific mechanisms responsible for force production. The purpose of this study was to develop a novel coupled framework of in situ and in silico methods to more precisely understand the relationship between injury location and force production deficits. We created a three-dimensional finite-element model of the pennate latissimus dorsi (LD) muscle in the rat and validated the model experimentally. We found that the model's prediction (2.6 N/g Model I, 2.1 N/g Model V) compared favorably to in situ testing of isometric force generation of the injured rat LD muscle (2.8 ± 0.3 N/g Experimental I, 2.0 ± 0.2 N/g Experimental V). Further model analysis revealed that the contribution from lateral and longitudinal force transmission to the total force varied with injury location and led to a greater understanding of the mechanisms responsible for VML-related force deficits. In the future, the coupled computational and experimental framework can be used to inform development of preclinical VML injury models that better recapitulate the spectrum of VML injuries observed in affected patients, and the mechanistic insight can accelerate the creation of improved regenerative therapeutics for VML injuries.
容积性肌肉损失损伤（VML）的治疗极具挑战性，因为伤口位置存在差异。再生医学提供了有前途的替代治疗方法，但对于 VML 损伤的严重程度与必须解决的相应功能缺陷之间的相关性知之甚少。需要有一种工具，可以阐明 VML 损伤与力量损失之间的关系，以及对负责产生力量的特定机制的影响。本研究的目的是开发一种新的原位和计算方法相结合的框架，以更准确地理解损伤位置与力量产生缺陷之间的关系。我们创建了一种大鼠羽状胸大肌（LD）的三维有限元模型，并通过实验对模型进行了验证。我们发现，该模型的预测（模型 I 为 2.6 N/g，模型 V 为 2.1 N/g）与受伤大鼠 LD 肌肉等长力量产生的原位测试结果（实验 I 为 2.8 ± 0.3 N/g，实验 V 为 2.0 ± 0.2 N/g）非常吻合。进一步的模型分析表明，来自侧向和纵向力传递的贡献对总力的影响因损伤位置而异，从而更深入地了解了导致 VML 相关力量缺陷的机制。在未来，这种结合计算和实验的框架可以用于指导开发更好地模拟受影响患者中观察到的 VML 损伤谱的临床前 VML 损伤模型，而机制上的深入了解可以加速开发用于 VML 损伤的改良再生治疗方法。
