Bioink development for multi-modal 3D-bioprinting of large tissues

Abstract text (incl. figure legends and references)

3D bioprinting shows promise in various applications, allowing for custom 3D shapes and intricate structures. Nevertheless, the challenge lies in successfully creating dense tissues. After the printing process cells require a considerable amount of time to mature and develop into functional biological tissues. Moreover, producing large-scale tissues presents another hurdle as it surpasses the diffusion limit for crucial substances necessary for survival.
We present a material combination suited for multi-modal 3D-bioprinting of larger tissues. Thus, our materials are specifically tailored not only for optimal printing qualities but also to meet the unique requirements of the cells. Further, mocroextruded channels ensure long-term nutrient supply.
Drop-on-demand and extrusion-based bioprinting techniques are selected based on material viscosity for ECM (polysaccharide-protein-blends) and sacrificial material (SM, gelatin) printing, respectively. Customizable bioinks are characterized by their rheological, mechanical, and surface properties. While those aspects are essential for printability, cytocompatibility and biofunctionality play a major role for cell survival and proliferation. Thus, the latter are evaluated to achieve the best results.
Cytocompatible concentrations of SM regarding gel-sol transition are printed into an ECM-like material which shows cell viabilities of >90 %. Further, the cell-filled ECM is printed into a custom bioreactor promoting medium flow into the channels to ensure nutrient supply to depths exceeding the oxygen diffusion limit.
Matrix and SM are customized to suit both DoD and extrusion-based bioprinting methods, ensuring they fulfill the necessary criteria for creating optimal cell conditions. Looking ahead, these innovative multi-modal bioprinting techniques show immense potential for enabling large-scale fabrication of perfusable tissues, which can greatly impact areas such as drug development and personalized medicine.