Volumetric muscle loss (VML) is the traumatic or surgical loss of skeletal muscle beyond the inherent regenerative capacity of the body, generally leading to severe functional deficit. Formation of appropriate somato-motor innervations remains one of the biggest challenges for both autologous grafts as well as tissue-engineered muscle constructs. We aim to address this challenge by developing pre-innervated tissue-engineered muscle comprised of long aligned networks of spinal motor neurons and skeletal myocytes on aligned nanofibrous scaffolds. Motor neurons led to enhanced differentiation and maturation of skeletal myocytes in vitro. These pre-innervated tissue-engineered muscle constructs when implanted in a rat VML model significantly increased satellite cell density, neuromuscular junction maintenance, graft revascularization, and muscle volume over three weeks as compared to myocyte-only constructs and nanofiber scaffolds alone. These pro-regenerative effects may enhance functional neuromuscular regeneration following VML, thereby improving the levels of functional recovery following these devastating injuries.

体积肌肉损失（VML）是骨骼肌的外伤或手术损失超出了身体固有的再生能力，通常会导致严重的功能缺陷。形成适当的躯体运动神经支配仍然是自体移植物和组织工程肌肉构造的最大挑战之一。我们的目标是通过开发预神经支配的组织工程肌肉来应对这一挑战，该肌肉由对齐的纳米纤维支架上的脊髓运动神经元和骨骼肌细胞的长对齐网络组成。运动神经元导致骨骼肌细胞在体外增强分化和成熟。与仅肌细胞结构和单独的纳米纤维支架相比，这些预神经支配的组织工程肌肉结构在植入大鼠 VML 模型时，在三周内显着增加了卫星细胞密度、神经肌肉接头维持、移植物血运重建和肌肉体积。这些促再生作用可能会增强 VML 后的功能性神经肌肉再生，从而提高这些毁灭性损伤后的功能恢复水平。