Volumetric muscle loss (VML) is a traumatic loss of muscle tissue that results in chronic functional impairment. When injured, skeletal muscle is capable of small-scale repair; however, regenerative capacities are lost with VML due to a critical loss stem cells and extracellular matrix (ECM). Consequences of VML include either long-term disability or delayed amputations of the affected limb. While the prevalence of VML is substantial, currently a successful clinical therapy has not been identified. In a previous study, an electrospun composed of polycaprolactone (PCL) and decellularized-ECM (D-ECM) supported satellite cell-mediated myogenic activity in vitro. In this study, we investigate the extent to which this electrospun scaffold can support functional muscle regeneration in a murine model of VML. Experimental groups included no treatment, pure PCL treated, and PCL:D-ECM (50:50 blend) treated VML defects. The PCL:D-ECM scaffold treated VML muscles supported increased activity of anti-inflammatory M2 macrophages (arginase+ ) at Day 28, compared to other experimental groups. Increased myofiber (MHC+ ) regeneration was observed histologically at both Days 7 and 28 post-trauma in blend scaffold treated group compared to PCL treated and untreated groups. However, improvements in muscle weights and force production were not observed. Future studies would evaluate muscle function at longer time-points post-VML injury to allow sufficient time for reinnervation of regenerated muscle fibers.

译文

体积肌肉损失 (VML) 是肌肉组织的创伤性损失,导致慢性功能障碍。受伤时,骨骼肌能够进行小规模修复; 但是,由于干细胞和细胞外基质 (ECM) 的严重损失,VML失去了再生能力。VML的后果包括长期残疾或患肢的截肢延迟。虽然VML的患病率很高,但目前尚未确定成功的临床治疗方法。在先前的研究中,由聚己内酯 (PCL) 和脱细胞ECM (d-ecm) 组成的电纺丝在体外支持卫星细胞介导的成肌活性。在这项研究中,我们研究了这种电纺支架在VML小鼠模型中支持功能性肌肉再生的程度。实验组包括未处理,纯PCL处理和PCL: d-ecm (50:50共混物) 处理的VML缺陷。与其他实验组相比,在第28天,经PCL: d-ecm支架处理的VML肌肉支持抗炎M2巨噬细胞 (精氨酸酶) 的活性增加。与PCL治疗组和未治疗组相比,在创伤后第7天和第28天的组织学观察到肌纤维 (MHC) 再生增加。然而,没有观察到肌肉重量和力量产生的改善。未来的研究将评估VML损伤后较长时间点的肌肉功能,以便有足够的时间重新支配再生的肌肉纤维。

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