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Biofabricating murine and human myo-substitutes for rapid volumetric muscle loss restoration
bioRxiv - Bioengineering Pub Date : 2020-05-30 , DOI: 10.1101/2020.05.25.114819
Marco Costantini , Stefano Testa , Ersilia Fornetti , Claudia Fuoco , Minghao Nie , Sergio Bernardini , Alberto Rainer , Jacopo Baldi , Carmine Zoccali , Roberto Biagini , Luisa Castagnoli , Libero Vitiello , Bert Blaauw , Dror Seliktar , Wojciech Święszkowski , Piotr Garstecki , Shoji Takeuchi , Gianni Cesareni , Stefano Cannata , Cesare Gargioli

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 along with muscle mass and force recovery. Together, 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.

中文翻译:

生物制造鼠类和人类肌代用品以快速恢复体积性肌肉丢失

骨骼肌组织的重要性无疑是几个重要功能的控制者,包括呼吸作用和所有自愿运动。但是,其再生能力有限,明显的组织损失通常会导致称为体积肌肉损失的慢性病理状况。在这里,我们提出了一种生物制造方法来快速恢复骨骼肌质量,3D组织结构和功能。通过概括微观水平上的肌肉各向异性组织,我们证明可以有效地指导细胞分化和肌束形成的体外和体内。值得注意的是,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-细胞存活和肌肉收缩功能的关键方面-以及先进的肌肉质量和力量恢复。总之,这些数据为进一步测试大型动物的肌替代物奠定了坚实的基础,并为最终转化为临床场景提供了有希望的平台。
更新日期:2020-05-30
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