Extracellular matrix remodelling induced by alternating electrical and mechanical stimulations increases the contraction of engineered skeletal muscle tissues
Extracellular matrix remodelling induced by alternating electrical and mechanical stimulations increases the contraction of engineered skeletal muscle tissues
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DOI：
10.1038/s41598-019-39522-6
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发表时间：
2019-02-25
影响因子：
4.6
通讯作者：
Asada, H. Harry
中科院分区：
文献类型：
--
作者：
Kim, Hyeonyu;Kim, Min-Cheol;Asada, H. Harry
工程骨骼肌在收缩力方面不如自然肌肉，阻碍了其在实际应用中的潜在应用。一个主要的限制是，细胞外基质(ECM)不仅阻碍收缩，而且不能有效地将肌管产生的力传递给负荷。在本研究中，细胞外基质重塑在短时间内提高了收缩力，而协调的电和机械刺激相结合的刺激诱导了所需的细胞外基质重塑。值得注意的是，对工程化肌肉施加单一和联合刺激可以重塑其ECM网络结构，这决定了ECM的机械性能。组织中的肌管串联和并联连接到细胞外基质。并联ECM的刚度必须较低，才不会阻碍收缩，而串联ECM的刚度必须较高，才能将力传递到负载。实验结果和力学模型都表明，通过协调的联合刺激使ECM纤维重新定向，从而降低了平行ECM的刚度，而增加了串联ECM的刚度。特别是，3分钟和20分钟的交替电刺激和机械刺激分别使力增加18%和31%。
Engineered skeletal muscles are inferior to natural muscles in terms of contractile force, hampering their potential use in practical applications. One major limitation is that the extracellular matrix ( ECM) not only impedes the contraction but also ineffectively transmits the forces generated by myotubes to the load. In the present study, ECM remodelling improves contractile force in a short time, and a coordinated, combined electrical and mechanical stimulation induces the desired ECM remodelling. Notably, the application of single and combined stimulations to the engineered muscles remodels the structure of their ECM networks, which determines the mechanical properties of the ECM. Myotubes in the tissues are connected in parallel and in series to the ECM. The stiffness of the parallel ECM must be low not to impede contraction, while the stiffness of the serial ECM must be high to transmit the forces to the load. Both the experimental results and the mechanistic model suggest that the combined stimulation through coordination reorients the ECM fibres in such a way that the parallel ECM stiffness is reduced, while the serial ECM stiffness is increased. In particular, 3 and 20 minutes of alternating electrical and mechanical stimulations increase the force by 18% and 31%, respectively.