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Structures in nature are often multi‐material, and their structures have a fine balance between segregation and aggregation (mixed, but not scrambled) that provides functionality. Chaotic fabrication, a technology that exploits the ability of chaotic advection to create predictable and reproducible multilayered structures, excels at producing materials where this balance can be achieved and finely tuned. This method is based on the use of chaotic mixing systems, which can produce constructs with highly organized internal micro‐architecture in a simple and cost‐effective way. This manuscript provides a perspective on how chaotic printing can be a great enabler in the manufacture of advanced materials, including living tissues. Chaotic printing may overcome many of the critical hurdles that are currently faced in manufacturing and biofabrication (e.g., creating a wide array of interfaces, reaching high resolutions rapidly and at low cost, and producing densely vascularized tissues). The manuscript introduces the technology, explains how the idea originated, presents a timeline that provides a recapitulation of the milestones achieved so far, describes the main characteristics, advantages, limitations, and challenges of the technology, and concludes with future perspectives on the evolution and use of this versatile method. [ABSTRACT FROM AUTHOR]

Nature abounds with micro‐architected materials containing layered multi‐material patterns that often transition within the very same monolithic piece. Fabricating these complex materials using current technologies is challenging. Multimaterial chaotic printing is presented—an extrusive printing method based on the use of chaotic advection—that can fabricate microstructured hydrogels with well‐defined multimaterial and multilayered micropatterns. Printheads containing internal Kenics static mixing (KSM) elements and top‐ and lateral‐positioned inlets are used to produce a wide repertoire of multilayered hydrogel filaments. In this plug‐and‐play system, the radial and axial micropatterns can be designed ad hoc by defining the printhead configuration (i.e., the number of KSM elements and inlets, and the inlet positions) and the flow program (i.e., activation/deactivation of the ink‐flow through each inlet). Computational fluid dynamics simulations closely predict the microstructure obtained by a given printhead configuration. The application of this platform is illustrated for easy fabrication of fibers with radial microgradients, bacterial ecosystems, structured emulsions, micro‐channeled hydrogel filaments, a pre‐vascularized tumor niche model, and skeletal muscle‐like tissues with axial and radial transitions of bioactive glass compartments. It is envisioned that multimaterial chaotic printing will be a valuable addition to the toolbox of additive manufacturing for the rational fabrication of advanced materials. [ABSTRACT FROM AUTHOR]

The neuromuscular junction (NMJ) plays a critical role in muscle contraction, and its dysfunction can result in various neuromuscular disorders. In vitro models for studying NMJ are essential for understanding their functions and pathology. However, the engineering of muscle tissue presents challenges for the organization of myofiber-like oriented muscle bundles as well as the induction of vessel formation and innervation. To address these challenges, we fabricated a hybrid muscle construct comprising uniaxially aligned muscle struts and endothelial cell spheroids using a combination of in situ electric field-assisted bioprinting (E-printing) and microdroplet-based spheroid-forming bioprinting (MDS-printing) techniques. This resulted in self-aggregation of human umbilical vein endothelial cells (HUVECs) into spheroids without attachment to the structures. We tested various fabrication parameters, such as electric field and cross-linking conditions, for E-printing and the deposited cell density of MDS-printing, to stabilize the alignment of the human muscle progenitor cells (hMPCs) and HUVEC spheroids, respectively. The stimulated hMPCs efficiently formed fully aligned myofibers, and the incorporation of HUVEC spheroids induced highly upregulated crosstalk between different cell types compared to a simple E-printed hMPC/HUVEC mixture-loaded construct. This improved myogenesis and vessel formation in vitro. In addition, when co-cultured with a motor neuron-like cell (NSC-34) spheroid separated by a channel, we observed considerably improved neuromuscular junction formation compared to those formed with the normally mixed cell-bearing structures. Our findings suggest that this hybrid muscle construct has the potential to enhance muscle tissue engineering by improving biological activities through the incorporation of HUVEC-spheroids and facilitating neuromuscular junction formation through co-culture with NSC-34 spheroids. [ABSTRACT FROM AUTHOR]

Hydrogel droplets with inner compartments are valuable in various fields, including tissue engineering. A droplet-based biofabrication method is presented for the chaos-assisted production of architected spheres (CAPAS) for the rapid generation of multilayered hydrogel spheres (ranging from 0.6 to 3.5 mm in diameter) at high-throughput rates (up to 2000 spheres per min). This method is based on the use of chaotic advection generated by a Kenics static mixer (KSM) nozzle. The configuration of the KSM (i.e., the number of mixing elements) determines the number of compartments within the sphere. Sphere size is adjusted by flow rate, printhead outlet diameter, polymer concentration (sodium alginate or gelatin-methacryloyl (GelMA)), and crosslinking bath composition. This versatile system operates in dripping and jetting modes, preserving multilayered architecture in both modes. Proof-of-concept experiments with breast cancer (MDA-MB-231), human dermal fibroblast (HDF), and murine myoblast (C2C12) lines show over 80% cell viability immediately post-fabrication, maintained over extended culture (14 or 30 days). CAPAS is used to create a breast cancer model with cancer-tissue-like and healthy-tissue-like micro-niches to test paclitaxel doses. It is envisioned that CAPAS will enable high-throughput fabrication of hydrogel spheres for tissue engineering, chemical engineering, and material sciences applications., (© 2024 Wiley‐VCH GmbH.)