Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland.
Department of Biology, Rome University Tor Vergata, Rome, Italy.
EMBO Mol Med. 2021 Mar 5;13(3):e12778. doi: 10.15252/emmm.202012778. Epub 2021 Feb 15.
The importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly restore skeletal muscle mass, 3D histoarchitecture, and functionality. By recapitulating muscle anisotropic organization at the microscale level, we demonstrate to efficiently guide cell differentiation and myobundle formation both in vitro and in vivo. Of note, upon implantation, the biofabricated myo-substitutes support the formation of new blood vessels and neuromuscular junctions-pivotal aspects for cell survival and muscle contractile functionalities-together with an advanced muscle mass and force recovery. Altogether, these data represent a solid base for further testing the myo-substitutes in large animal size and a promising platform to be eventually translated into clinical scenarios.
骨骼肌组织的重要性毋庸置疑，它控制着包括呼吸和所有自主运动活动在内的多种重要功能。然而，其再生能力有限，大量组织损失通常会导致一种慢性病理状况，即容积性肌肉丧失。在这里，我们提出了一种生物制造方法，可快速恢复骨骼肌质量、3D 组织架构和功能。通过在微观水平上再现肌肉各向异性组织，我们证明了它能够在体外和体内有效地指导细胞分化和肌纤维束的形成。值得注意的是，在植入后，生物制造的肌替代物支持新血管和神经肌肉接头的形成，这是细胞存活和肌肉收缩功能的关键方面，同时还具有先进的肌肉质量和力量恢复。总的来说，这些数据为进一步在大型动物模型中测试肌替代物奠定了坚实的基础，也为最终转化为临床应用提供了一个有前途的平台。
