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Embedded 3D bioprinting has great value for the freeform fabrication of living matter. However, embedded 3D bioprinting is currently limited to highly viscous liquid baths or liquid‐like solid baths. In contrast, prior to crosslinking, most hydrogels are formulated as low‐viscosity solutions and are therefore not directly compatible with bioprinting due to low shape fidelity and poor print stability. The authors here present a method to enable low‐viscosity ink 3D (LoV3D) bioprinting, based on aqueous two‐phase stabilization of the ink‐bath interface. LoV3D allows for the printing of living constructs at high extrusion speeds (up to 1.8 m s−1) with high viability due to its exceedingly low‐viscosity. Moreover, LoV3D liquid/liquid interfaces offer unique advantages for fusing printed structures, creating intricate vasculature, and modifying surfaces at higher efficiencies than traditional systems. Furthermore, the low interfacial tension of LoV3D bioprinting offers unprecedented nozzle‐independent control over filament diameter via large‐dimension strand‐thinning, which allows for the printing of an exceptionally wide range of diameters down to the width of a single cell. Overall, LoV3D bioprinting is a unique all‐aqueous approach with broad material compatibility without the need for rheological ink adaption, which opens new avenues of application in cell patterning, drug screening, engineered meat, and organ fabrication.

Bioengineering of tissues and organs has the potential to generate functional replacement organs. However, achieving the full-thickness vascularization that is required for long-term survival of living implants has remained a grand challenge, especially for clinically sized implants. During the pre-vascular phase, implanted engineered tissues are forced to metabolically rely on the diffusion of nutrients from adjacent host-tissue, which for larger living implants results in anoxia, cell death, and ultimately implant failure. Here it is reported that this challenge can be addressed by engineering self-oxygenating tissues, which is achieved via the incorporation of hydrophobic oxygen-generating micromaterials into engineered tissues. Self-oxygenation of tissues transforms anoxic stresses into hypoxic stimulation in a homogenous and tissue sizeindependent manner. The in situ elevation of oxygen tension enables the sustained production of high quantities of angiogenic factors by implanted cells, which are offered a metabolically protected pro-angiogenic microenvironment. Numerical simulations predict that self-oxygenation of living tissues will effectively orchestrate rapid full-thickness vascularization of implanted tissues, which is empirically confirmed via in vivo experimentation. Self-oxygenation of tissues thus represents a novel, effective, and widely applicable strategy to enable the vascularization living implants, which is expected to advance organ transplantation and regenerative medicine applications.

In additive manufacturing, bioink formulations govern strategies to engineer 3D living tissues that mimic the complex architectures and functions of native tissues for successful tissue regeneration. Conventional 3D-printed tissues are limited in their ability to alter the fate of laden cells. Specifically, the efficient delivery of gene expression regulators (i.e., microRNAs) to cells in bioprinted tissues has remained largely elusive. In this study, we explored the inclusion of extracellular vesicles (EVs), naturally occurring nanovesicles (NVs), into bioinks to resolve this challenge. EVs show excellent biocompatibility, rapid endocytosis, and low immunogenicity, which lead to the efficient delivery of microRNAs without measurable cytotoxicity. EVs were fused with liposomes to prolong and control their release by altering their physical interaction with the bioink. Hybrid EVs-liposome (hEL) NVs were embedded in gelatin-based hydrogels to create bioinks that could efficiently encapsulate and deliver microRNAs at the target site in a controlled and sustained manner. The regulation of cells’ gene expression in a 3D bioprinted matrix was achieved using the hELs-laden bioink as a precursor for excellent shape fidelity and high cell viability constructs. Novel bioprinting approaches of regulatory factors-loaded bioinks will expedite the clinical translation of these products for treating tissue injury.

Exchangeable microfluidic nozzles enable the facile production of a wide variety of micromaterials using a single cleanroom-free manufactured microfluidic device.

Oxygen releasing biomaterials can facilitate the survival of living implants by creating environments with a viable oxygen level. Hydrophobic oxygen generating microparticles (HOGMPs) encapsulated calcium peroxide (CPO) have recently been used in tissue engineering to release physiologically relevant amounts of oxygen for several weeks. However, generating oxygen using CPO is mediated via the generation of toxic levels of hydrogen peroxide (H 2 O 2 ). The incorporation of antioxidants, such as catalases, can potentially reduce H 2 O 2 levels. However, the formulation in which catalases can most effectively scavenge H 2 O 2 within oxygen generating biomaterials has remained unexplored. In this study, three distinct catalase incorporation methods are compared based on their ability to decrease H 2 O 2 levels. Specifically, catalase is incorporated within HOGMPs, or absorbed onto HOGMPs, or freely laden into the hydrogel entrapping HOGMPs and compared with control without catalase. Supplementation of free catalase in an HOGMP-laden hydrogel significantly decreases H 2 O 2 levels reflecting a higher cellular viability and metabolic activity of all the groups. An HOGMP/catalase-laden hydrogel precursor solution containing cells is used as an oxygenating bioink allowing improved viability of printed constructs under severe hypoxic conditions. The combination of HOGMPs with a catalase-laden hydrogel has the potential to decrease peroxide toxicity of oxygen generating tissues.

Embedded Bioprinting In article number 2204609 by Jeroen Leijten and co‐workers, liquid‐in‐liquid printing of low viscous solutions is enabled by the novel use of aqueous two‐phase systems. Use of low viscous solutions allows for cytocompatible biofabrication of embedded sacrificial strands with an exceptionally large resolution range. The low viscous nature of bio‐ink also allows for direct printing of intricate, interconnected, and perfusable networks within 3D structures.

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