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.
The on-demand generation of viscous microdroplets to print functional or biological materials remains challenging using conventional inkjet-printing methods, mainly due to aggregation and clogging issues. In an effort to overcome these limitations, we implement a jetting method to print viscous microdroplets by laser-induced shockwaves. We experimentally investigate the dependence of the jetting regimes and the droplet size on the laser-pulse energy and on the inks' physical properties. The range of printable liquids with our device is significantly extended compared to conventional inkjet printers's performances. In addition, the laser-induced flow-focusing phenomenon allows us to controllably generate viscous microdroplets up to 210 mPa s with a diameter smaller than the nozzle from which they originated (200 μm). Inks containing proteins are printed without altering their functional properties, thus demonstrating that this jetting technique is potentially suitable for bioprinting.
Cell‐laden hydrogels used in tissue engineering generally lack sufficient 3D topographical guidance for cells to mature into aligned tissues. A new strategy called filamented light (FLight) biofabrication rapidly creates hydrogels composed of unidirectional microfilament networks, with diameters on the length scale of single cells. Due to optical modulation instability, a light beam is divided optically into FLight beams. Local polymerization of a photoactive resin is triggered, leading to local increase in refractive index, which itself creates self‐focusing waveguides and further polymerization of photoresin into long hydrogel microfilaments. Diameter and spacing of the microfilaments can be tuned from 2 to 30 µm by changing the coherence length of the light beam. Microfilaments show outstanding cell instructive properties with fibroblasts, tenocytes, endothelial cells, and myoblasts, influencing cell alignment, nuclear deformation, and extracellular matrix deposition. FLight is compatible with multiple types of photoresins and allows for biofabrication of centimeter‐scale hydrogel constructs with excellent cell viability within seconds (<10 s per construct). Multidirectional microfilaments are achievable within a single hydrogel construct by changing the direction of FLight projection, and complex multimaterial/multicellular tissue‐engineered constructs are possible by sequentially exchanging the cell‐laden photoresin. FLight offers a transformational approach to developing anisotropic tissues using photo‐crosslinkable biomaterials.
Volumetric Bioprinting Volumetric bioprinting shapes organoid‐laden constructs into centimeter‐scale assemblies that mimic native liver function. In article number 2110054, Riccardo Levato and co‐workers report the development of a hydrogel‐based bioresin with tunable optical properties to minimize scattering in light‐based printing and ensure high resolution. Organoid viability and maturation is preserved by the shear‐stress‐free printing, and salient liver functions mature in response to the 3D bioprinted architecture.
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