From 3D printed molds to bioprinted scaffolds: A hybrid material extrusion and vat polymerization bioprinting approach for soft matter constructs

Abstract

Three-dimensional (3D) bioprinting methods vary in difficulty and complexity depending on the application desired and biomaterials used. 3D biofabrication is gaining increased traction with enhanced additive manufacturing technologies. Yet, high print resolution and efficiency for the fabrication of complex constructs still prove to be challenging. An intricate balance between biomaterial composition, machine maneuverability, and extrusion mechanism is required. While soft bioinks are highly desirable when used as a biodegradable scaffold material for tissue and organ fabrication, mechanical stiffness and shape fidelity are often compromised. Alternately, post-printing ultraviolet and chemical crosslinking processes improve fidelity but threaten cell viability. Herein, we propose a hybrid fabrication approach to facilitate 3D bioprinting using soft bioinks with instantaneous gelation properties while maintaining shape fidelity for tissue and organ structures of complex geometries. The approach entails a multi-step “3D Printed Molds to Scaffolds” method, which uses additive manufacturing to create accurate negative support structures for the desired construct. A tissue or organ model is first designed in computer-aided design (CAD) modeling software to create a negative mold structure of the desired tissue or organ. Using a Formlabs® SLA 3D printer, the negative mold is fabricated at desired scale using a biocompatible elastic resin. Then, a robotic 3D bioprinting system is loaded with a sliced g-code of the CAD model. The robot start position is aligned with the placement of the fabricated mold on the printbed. Microfluidic pumps deliver three solutions through a customized nozzle to extrude peptide bioink, which gels instantaneously. The initial layers of the structure are formed within the mold to create a solid foundation of the construct. The hybrid approach was found to enhance fidelity considerably and enabled the printing of a complex human ear structure. It is promising for tissue and organ fabrication as it offers a cost-effective support structure without increasing printing time. It could also be used as a rapid prototyping approach for researchers who do not have access to 3D bioprinting systems. Biofabrication, from printed molds to bioprinted scaffolds, will potentially enhance the printing experience with soft bioinks while preserving cell durability and viability.