Biofabrication technologies, including stereolithography and extrusion‐based printing, are revolutionizing the creation of complex engineered tissues. The current paradigm in bioprinting relies on the additive layer‐by‐layer deposition and assembly of repetitive building blocks, typically cell‐laden hydrogel fibers or voxels, single cells, or cellular aggregates. The scalability of these additive manufacturing technologies is limited by their printing velocity, as lengthy biofabrication processes impair cell functionality. Overcoming such limitations, the volumetric bioprinting of clinically relevant sized, anatomically shaped constructs, in a time frame ranging from seconds to tens of seconds is described. An optical‐tomography‐inspired printing approach, based on visible light projection, is developed to generate cell‐laden tissue constructs with high viability (>85%) from gelatin‐based photoresponsive hydrogels. Free‐form architectures, difficult to reproduce with conventional printing, are obtained, including anatomically correct trabecular bone models with embedded angiogenic sprouts and meniscal grafts. The latter undergoes maturation in vitro as the bioprinted chondroprogenitor cells synthesize neo‐fibrocartilage matrix. Moreover, free‐floating structures are generated, as demonstrated by printing functional hydrogel‐based ball‐and‐cage fluidic valves. Volumetric bioprinting permits the creation of geometrically complex, centimeter‐scale constructs at an unprecedented printing velocity, opening new avenues for upscaling the production of hydrogel‐based constructs and for their application in tissue engineering, regenerative medicine, and soft robotics.
In tomographic volumetric additive manufacturing, an entire three-dimensional object is simultaneously solidified by irradiating a liquid photopolymer volume from multiple angles with dynamic light patterns. Though tomographic additive manufacturing has the potential to produce complex parts with a higher throughput and a wider range of printable materials than layer-by-layer additive manufacturing, its resolution currently remains limited to 300 µm. Here, we show that a low-étendue illumination system enables the production of highresolution features. We further demonstrate an integrated feedback system to accurately control the photopolymerization kinetics over the entire build volume and improve the geometric fidelity of the object solidification. Hard and soft centimeter-scale parts are produced in less than 30 seconds with 80 µm positive and 500 µm negative features, thus demonstrating that tomographic additive manufacturing is potentially suitable for the ultrafast fabrication of advanced and functional constructs.
Organ‐ and tissue‐level biological functions are intimately linked to microscale cell–cell interactions and to the overarching tissue architecture. Together, biofabrication and organoid technologies offer the unique potential to engineer multi‐scale living constructs, with cellular microenvironments formed by stem cell self‐assembled structures embedded in customizable bioprinted geometries. This study introduces the volumetric bioprinting of complex organoid‐laden constructs, which capture key functions of the human liver. Volumetric bioprinting via optical tomography shapes organoid‐laden gelatin hydrogels into complex centimeter‐scale 3D structures in under 20 s. Optically tuned bioresins enable refractive index matching of specific intracellular structures, countering the disruptive impact of cell‐mediated light scattering on printing resolution. This layerless, nozzle‐free technique poses no harmful mechanical stresses on organoids, resulting in superior viability and morphology preservation post‐printing. Bioprinted organoids undergo hepatocytic differentiation showing albumin synthesis, liver‐specific enzyme activity, and remarkably acquired native‐like polarization. Organoids embedded within low stiffness gelatins (<2 kPa) are bioprinted into mathematically defined lattices with varying degrees of pore network tortuosity, and cultured under perfusion. These structures act as metabolic biofactories in which liver‐specific ammonia detoxification can be enhanced by the architectural profile of the constructs. This technology opens up new possibilities for regenerative medicine and personalized drug testing.
3D printing has revolutionized the manufacturing of volumetric components and structures in many areas. Several fully volumetric light‐based techniques have been recently developed thanks to the advent of photocurable resins, promising to reach unprecedented short print time (down to a few tens of seconds) while keeping a good resolution (around 100 μm). However, these new approaches only work with homogeneous and relatively transparent resins so that the light patterns used for photo‐polymerization are not scrambled along their propagation. Herein, a method that takes into account light scattering in the resin prior to computing projection patterns is proposed. Using a tomographic volumetric printer, it is experimentally demonstrated that implementation of this correction is critical when printing objects whose size exceeds the scattering mean free path. To show the broad applicability of the technique, functional objects of high print fidelity are fabricated in hard organic scattering acrylates and soft cell‐laden hydrogels (at 4 million cells mL −1 ). This opens up promising perspectives in printing inside turbid materials with particular interesting applications for bioprinting cell‐laden constructs.
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