Functional Skeletal Muscle Regeneration with Thermally Drawn Porous Fibers and Reprogrammed Muscle Progenitors for Volumetric Muscle Injury

Skeletal muscle has an inherent capacity for spontaneous regeneration. However, recovery after severe injuries such as volumetric muscle loss (VML) is limited. There is therefore a need to develop interventions to induce functional skeletal muscle restoration. One suggested approach includes tissue-engineered muscle constructs. Tissue-engineering treatments have so far been impeded by the lack of reliable cell sources and the challenges in engineering of suitable tissue scaffolds. To address these challenges, muscle extracellular matrix (MEM) and induced skeletal myogenic progenitor cells (iMPCs) are integrated within thermally drawn fiber based microchannel scaffolds. The microchannel fibers decorated with MEM enhance differentiation and maturation of iMPCs. Furthermore, engraftment of these bioengineered hybrid muscle constructs induce de novo muscle regeneration accompanied with microvessel and neuromuscular junction formation in a VML mouse model, ultimately leading to functional recovery of muscle activity.

骨骼肌具有自发再生的固有能力。然而，在诸如肌肉容积性缺失（VML）等严重损伤后的恢复是有限的。因此，有必要开发干预措施以诱导功能性骨骼肌修复。一种被提出的方法包括组织工程化的肌肉构建体。到目前为止，由于缺乏可靠的细胞来源以及在构建合适的组织支架方面存在挑战，组织工程治疗受到了阻碍。为了应对这些挑战，将肌肉细胞外基质（MEM）和诱导性骨骼肌祖细胞（iMPCs）整合在基于热拉伸纤维的微通道支架内。用MEM修饰的微通道纤维促进了iMPCs的分化和成熟。此外，在VML小鼠模型中，这些生物工程混合肌肉构建体的植入诱导了新生肌肉再生，并伴有微血管和神经肌肉接头的形成，最终导致肌肉活动的功能恢复。