Multiscale engineered human skeletal muscles with perfusable vasculature and microvascular network recapitulating the fluid compartments

Creating a vasculature in engineered human skeletal muscle tissues (ehSMTs) enables us to create thick tissues, increase cell survival in implantation, provide models of blood-organ barriers for drug testing, and enhance muscle differentiation through paracrine signaling. Here, contractile ehSMTs with a central perfusable vascular channel and microvascular networks growing from this central vasculature into the surrounding skeletal muscle tissue were newly demonstrated. Because coculturing muscle cells and endothelial cells requires incompatible media, we recapitulated the in vivo extracellular fluid compartments between blood plasma and interstitial fluid by creating an in vitro perfusable vasculature running through skeletal muscle tissue with a physiologic cell density. By using this model, we constructed large vascularized ehSMTs and showed the potential to be utilized for drug testing platforms. Also, we found that coculturing with two separate media from an early stage of muscle differentiation led to increased contractile force, thicker myotubes, and improved muscle differentiation.

Automated summary

Creating a vasculature in engineered human skeletal muscle tissues has various advantages, including increasing tissue thickness, improving cell survival, providing models for drug testing, and enhancing muscle differentiation. The researchers demonstrated the creation of contractile skeletal muscle tissues with a central vascular channel and microvascular networks. By recreating the in vivo extracellular fluid compartments, they were able to construct large vascularized skeletal muscle tissues for drug testing platforms. Coculturing with incompatible media from an early stage of muscle differentiation led to improved muscle differentiation and contractile force.