Composite Biomaterials as Long-lasting Scaffolds for 3D Bioprinting of Highly Aligned Muscle Tissue

2019 edition

Andrea Garc├şa Lizarribar

In vitro developed three-dimensional tissues are becoming a need for tissue engineering, such as skeletal muscle tissue. Hydrogels are being used as supporting biomaterials for the growth and differentiation of the cells. They have to mimic the environment of the cells in the original tissue, as the mechanical properties, degradability, biocompatibility and space distribution. These materials can be combined with 3D-bioprinting techniques, which allow the user to control the spatial configuration and dimensions of the tissue. Nevertheless, it is difficult to obtain a biomaterial that meets all the needs required for tissue engineering. Non-modified animal-derived biomaterials, such as collagen and fibrinogen, present high biocompatibility and myogenicity. However, those materials are fast degraded by the embedded cells and they present poor mechanical properties. Moreover, the physical properties of those materials are not the most suitable for bioprinting, as it is difficult to obtain accurate and stable structures and, consequently, the spatial conformation of the tissue. In this work, we combine gelatin methacryloil (GelMA), a modified animal-derived material, with two natural non-animal-derived materials, alginate methacrylate (AlgMA) and carboxymethyl cellulose methacrylate (CMCMA), and a synthetic commercial one, PEGDA. We make a comparative study of the physical properties of these photopolymerizable composite hydrogels using GelMA as the reference material. We compare the 3D growth and differentiation of C2C12 mouse myoblast in those mechanically tunable composites. Finally, we use bioprinting methods to obtain spatially controlled highly aligned myotubes that mimic the structure of the muscle fascicles, which is a primary requisite for skeletal muscle tissue engineering.