Rapid Deep Vat Printing Using Photoclickable Collagen-Based Bioresins.

Abstract

Deep vat printing (DVP) techniques, including tomographic and filamented light (Flight) printing have transformed the tissue engineering landscape by enabling layer-free bioprinting at high resolution and speeds. Importantly, collagen is one of the most widely used materials in tissue biofabrication, but DVP using collagen-based photoresins has been under-explored. In this work, photoclickable collagen-based resins are demonstrated which are compatible with DVP, enabling prints with up to 50 µm print resolution and speeds less than 20 s per cm³. These resins contain iodixanol, which acts as a refractive index matching agent to reduce optical inhomogeneities by added cells and improves the stability of the collagen-based resins under neutralized conditions. As a potential application, multi-material tomographic and FLight printing is demonstrated to create intricate tissue constructs featuring muscle and connective tissue interfaces. While tomographic printing allows greater complexity over the overall shape of the constructs, FLight constructs demonstrate enhanced biomimicry through generation of aligned multinucleated myotubes, transition zones between the two cell types, and regularly spaced sarcomere structure (≈2.6 µm average sarcomere length) which facilitates contractility in the muscle regions. The demonstration of photoclickable, isotonic and neutral collagen-based bioresins offers a new solution for DVP of biomimetic complex tissues and grafts.