Soft perfusion bioreactor to engineer skeletal muscle 3D volumetric constructs onto a porous scaffold.

3D skeletal muscle cell cultures are a promising tool to recapitulate $in vitro$ the physiological conditions found in the native biological tissue. However, it is still a challenge to deliver oxygen in avascular cell constructs thicker than $450 \mu m.$ In this study we manage to develop an all-soft perfusion bioreactor to engineer skeletal muscle tissue constructs at the macroscale onto a porous scaffold. The device is composed of a macroporous polyurethane scaffold matching the muscle stiffness, that is first wrapped in a compliant silicon chamber, and then sealed at the edges with two hollow tendon-like structures. After device assembly, the scaffold surface was conjugated with fibronectin proteins to allow myoblasts' adhesion onto its surface. Dynamic cell cultures performed using a peristaltic pump attested the ability of the device to enable 3D skeletal muscle cell cultures with a volume of $1 {cm^{3}}$. We strongly believe that the proposed device can recreate a native tissue environment while administering cells with multiple external stimuli, thus holding the potential of boosting skeletal muscle tissue engineering at its limits.