Using drugs, machines, and genes to engineer functional muscle

组织工程的目标是利用支架材料和多能干细胞制造组织替代物。在工程肌肉中，由于肌肉的功能是产生力，因此支架必须具有柔韧性和可生物降解性，这使得这一点变得更加复杂。虽然朝着这个目标已经取得了很大的进展，但仍然存在一些障碍，包括：1)工程肌肉的血管化；2)在肌肉和骨骼/人工材料之间建立有效的界面；3)肌肉成熟，因为它发育受阻；4)发育正常的肌纤维大小和力量。结果是，目前最先进的组织工程肌肉只有0.2毫米厚，产生的相对力量最多是新生儿肌肉的35%。为了使工程肌肉更大，增加其力量产生，我们建议使用药物来去除肌肉生长和发育的抑制剂，使用机器来拉伸和电刺激肌肉生长和发育，以及使用基因来增加肌肉纤维的大小，从而增加力量产生。该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，试图在培养中制造出更大、更强壮、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.