Muscle regeneration can be permanently impaired by traumatic injuries, despite the high regenerative capacity of skeletal muscle. Implantation of engineered biomimetic scaffolds to the site of muscle ablation may serve as an attractive off-the-shelf therapeutic approach. The objective of the study was to histologically assess the therapeutic benefit of a three-dimensional spatially patterned collagen scaffold, in conjunction with rehabilitative exercise, for treatment of volumetric muscle loss. To mimic the physiologic organization of skeletal muscle, which is generally composed of myofibers aligned in parallel, three-dimensional parallel-aligned nanofibrillar collagen scaffolds were fabricated. When implanted into the ablated murine tibialis anterior muscle, the aligned nanofibrillar scaffolds, in conjunction with voluntary caged wheel exercise, significantly improved the density of perfused microvessels, in comparison to treatments of the randomly oriented nanofibrillar scaffold, decellularized scaffold, or in the untreated control group. The abundance of neuromuscular junctions was 19-fold higher when treated with aligned nanofibrillar scaffolds in conjunction with exercise, in comparison to treatment of aligned scaffold without exercise. Although, the density of de novo myofibers was not significantly improved by aligned scaffolds, regardless of exercise activity, the cross-sectional area of regenerating myofibers was increased by > 60% when treated with either aligned and randomly oriented scaffolds, in comparison to treatment of decellularized scaffold or untreated controls. These findings demonstrate that voluntary exercise improved the regenerative effect of aligned scaffolds by augmenting neurovascularization, and have important implications in the design of engineered biomimetic scaffolds for treatment of traumatic muscle injury.

尽管骨骼肌具有很高的再生能力，但外伤可能会永久性损害肌肉的再生。工程仿生支架植入到肌肉消融部位可能是一种有吸引力的现成治疗方法。该研究的目的是在组织学上评估三维空间格局的胶原蛋白支架与康复运动相结合治疗体积性肌肉丢失的治疗效果。为了模拟骨骼肌的生理组织，骨骼肌通常由平行排列的肌纤维组成，制作了三维平行排列的纳米原纤胶原支架。当将其植入消融的小鼠胫骨前肌中时，对齐的纳米原纤维支架与自愿性笼养轮运动结合在一起，与随机取向的纳米原纤维支架，脱细胞支架或未治疗的对照组相比，显着提高了灌注微血管的密度。与不运动的定向支架治疗相比，经定向的纳米原纤维支架与运动结合治疗时，神经肌肉接头的丰度高19倍。尽管对齐的支架不能显着改善新生肌纤维的密度，但无论运动活动如何，与对齐和随机取向的支架相比，再生肌纤维的截面积均增加了60％以上。去细胞支架或未处理的对照。