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Our ability to produce human-scale biomanufactured organs is limited by inadequate vascularization and perfusion. For arbitrarily complex geometries, designing and printing vasculature capable of adequate perfusion poses a major hurdle. We introduce a model-driven design platform that demonstrates rapid synthetic vascular model generation alongside multifidelity computational fluid dynamics simulations and three-dimensional bioprinting. Key algorithmic advances accelerate vascular generation 230-fold and enable application to arbitrarily complex shapes. We demonstrate that organ-scale vascular network models can be generated and used to computationally vascularize >200 engineered and anatomic models. Synthetic vascular perfusion improves cell viability in fabricated living-tissue constructs. This platform enables the rapid, scalable vascular model generation and fluid physics analysis for biomanufactured tissues that are necessary for future scale-up and production. 

Abstract Three-dimensional (3D) bioprinting seeks to unlock the rapid generation of complex tissue constructs, but long-standing challenges with efficient in vitro microvascularization must be solved before this can become a reality. Microvasculature is particularly challenging to biofabricate due to the presence of a hollow lumen, a hierarchically branched network topology, and a complex signaling milieu. All of these characteristics are required for proper microvascular—and, thus, tissue—function. While several techniques have been developed to address distinct portions of this microvascularization challenge, no single approach is capable of simultaneously recreating all three microvascular characteristics. In this review, we present a three-part framework that proposes integration of existing techniques to generate mature microvascular constructs. First, extrusion-based 3D bioprinting creates a mesoscale foundation of hollow, endothelialized channels. Second, biochemical and biophysical cues induce endothelial sprouting to create a capillary-mimetic network. Third, the construct is conditioned to enhance network maturity. Across all three of these stages, we highlight the potential for extrusion-based bioprinting to become a central technique for engineering hierarchical microvasculature. We envision that the successful biofabrication of functionally engineered microvasculature will address a critical need in tissue engineering, and propel further advances in regenerative medicine and ex vivo human tissue modeling. 

Engineering organ-specific tissues for therapeutic applications is a grand challenge, requiring the fabrication and maintenance of densely cellular constructs composed of ~10 8 cells/ml. Organ building blocks (OBBs) composed of patient-specific–induced pluripotent stem cell–derived organoids offer a pathway to achieving tissues with the requisite cellular density, microarchitecture, and function. However, to date, scant attention has been devoted to their assembly into 3D tissue constructs. Here, we report a biomanufacturing method for assembling hundreds of thousands of these OBBs into living matrices with high cellular density into which perfusable vascular channels are introduced via embedded three-dimensional bioprinting. The OBB matrices exhibit the desired self-healing, viscoplastic behavior required for sacrificial writing into functional tissue (SWIFT). As an exemplar, we created a perfusable cardiac tissue that fuses and beats synchronously over a 7-day period. Our SWIFT biomanufacturing method enables the rapid assembly of perfusable patient- and organ-specific tissues at therapeutic scales. 

Abstract We present an analysis of helium ion (He⁺) fraction in an altitude range from about 400 km to around 700 km and its relationship to the ion temperature (T_i) and the vertical ion drift under solar maximum conditions. The data were obtained from the Arecibo incoherent scatter radar during 27 September to 1 October 2014 and 16–20 December 2014. The large He⁺fraction (>10%) lasts 15 hr per day during the winter solstice, which is 3 times larger than during fall equinox. This difference is caused by the more persistent downward ion drift in the winter. The incremental He⁺fraction and incrementalT_iare well anticorrelated, and the anticorrelation is more prominent during the daytime. These characteristics are associated with whether O⁺and He⁺are in diffusive equilibrium. During nighttime, we show that the vertical ion flow is downward causing the He⁺layer peak altitude to move to an altitude of 500 km from above 650 km. According to our analysis, He⁺fraction has to be larger than two thirds for diffusive equilibrium to occur above the He⁺peak height. Therefore, above the He⁺peak altitude, O⁺and He⁺cannot be in diffusive equilibrium with He⁺being the minor species. The vertical ion flow plays an important role in determining the diurnal variation and seasonal difference of He⁺distribution and whether He⁺is in a diffusive equilibrium with O⁺.