Integrating Synthetic and Biomaterial Embedded 3D Printing for the Development of Biohybrid Systems

Biohybrid systems, which are comprised of biological and synthetic materials, can be utilized for a variety of applications, ranging from new robotics, prostheses, and medical techniques to in vitro model systems and diagnosis platforms. Despite their versatility, the widespread fabrication and adoption of these systems has been limited, which can be attributed to the inability to fabricate the system and its constituents efficiently. Tedious, multistep assembly is often needed to build current biohybrid systems. By harnessing the power of 3D printing, and specifically the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) bioprinting platform, these systems can be fabricated in one step. In this work, I sought to integrate synthetic and biological printing in the creation of a biohybrid system by (1) improving synthetic printing in embedded printing systems and (2) engineering biomimetic skeletal muscle tissue. To achieve the first, I investigated the interdependence of rheology and machine pathing during FRESH printing of silicone elastomers, which is the material of choice for the synthetic framework of the biohybrid system. In doing so, I was able to improve silicone printing in various support baths. To achieve the second, I designed and FRESH printed type I collagen scaffolds that recapitulated native muscle fiber orientation and organization, which directly impacts muscle deformation during contraction and ultimately its function. By seeding these scaffolds with cell-laden hydrogels, cell-mediated compaction occurred, driving cellular infiltration through the voids of the scaffold, and the printed collagen filaments provided contact guidance to myoblasts, facilitating differentiation into multinucleated myotubes. Finally, I integrated synthetic and biomaterial embedded printing into the FRESH platform, which enabled dual printing of a silicone elastomer and a high-density C2C12 bioink for the fabrication of a biohybrid system. The results of this work lay down the foundation for the development and creation of more complex multimaterial biohybrid systems for a variety of applications.