Using drugs, machines, and genes to engineer functional muscle

组织工程学的目标是使用支架材料和多能干细胞来产生组织替代物。在工程肌肉中，这一点变得更加复杂，因为肌肉的功能是产生力量，因此支架必须是顺应性的和可生物降解的。虽然在实现这一目标方面取得了很大进展，但仍然存在一些障碍，包括：1)工程化肌肉的血管化；2)在肌肉和骨骼/人造材料之间建立有效的界面；3)肌肉成熟，因为它处于发育停滞状态；以及4)正常肌肉纤维的大小和力量的发育。结果是，目前最先进的组织工程肌肉厚度为0.2毫米，最多只能产生新生儿肌肉相对力量的35%。为了使工程肌肉变得更大并增加其力量生产，我们建议使用药物来消除肌肉生长和发育的抑制因素，使用机器来拉伸和电刺激肌肉生长和发展，以及使用基因来增加肌肉纤维大小从而促进生产。这项研究将在体内研究肌肉生理学的发现与我们的工程肌肉模型相结合，试图在培养中培养出更大、更强壮和更成熟的肌肉。

The goal of tissue engineering is to use scaffolding materials and multipotent stem cells to produce tissue replacements. In engineering muscle, this is made more complex by the fact that the function of muscle is to produce force and therefore the scaffold has to be compliant and biodegradable. While great progress has been made towards this goal, a number of obstacles remain, including: 1) vascularization of the engineered muscle; 2) creation of effective interfaces between muscle and bone/artificial materials; 3) maturation of the muscle, since it is developmentally arrested; and 4) the development of normal muscle fibre size and strength. The result is that the current state-of-the-art tissue engineered muscles are 0.2mm thick and produce at best 35% of the relative force of a neonatal muscle. In order to make the engineered muscles bigger and increase their force production, we propose to use drugs to remove inhibitors of muscle growth and development, machines to stretch and electrically stimulate muscle growth and development, and genes to increase muscle fibre size and therefore force production. The research combines discoveries made in vivo studying muscle physiology with our engineered muscle model to try to make bigger, stronger and more adult muscle in culture.