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Free, publicly-accessible full text available July 1, 2027
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Free, publicly-accessible full text available October 15, 2026
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Tissue engineering offers immense potential for addressing the unmet needs in repairing tissue damage and organ failure. Vascularization, the development of intricate blood vessel networks, is crucial for the survival and functions of engineered tissues. Nevertheless, the persistent challenge of ensuring an ample nutrient supply within implanted tissues remains, primarily due to the inadequate formation of blood vessels. This issue underscores the vital role of the human vascular system in sustaining cellular functions, facilitating nutrient exchange, and removing metabolic waste products. In response to this challenge, new approaches have been explored. Microfluidic devices, emulating natural blood vessels, serve as valuable tools for investigating angiogenesis and allowing the formation of microvascular networks. In parallel, bioprinting technologies enable precise placement of cells and biomaterials, culminating in vascular structures that closely resemble the native vessels. To this end, the synergy of microfluidics and bioprinting has further opened up exciting possibilities in vascularization, encompassing innovations such as microfluidic bioprinting. These advancements hold great promise in regenerative medicine, facilitating the creation of functional tissues for applications ranging from transplantation to disease modeling and drug testing. This review explores the potentially transformative impact of microfluidic and bioprinting technologies on vascularization strategies within the scope of tissue engineering.more » « less
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Engineered living systems (ELSs) represent purpose‐driven assemblies of living components, encompassing cells, biomaterials, and active agents, intricately designed to fulfill diverse biomedical applications. Gelatin and its derivatives have been used extensively in ELSs owing to their mature translational pathways, favorable biological properties, and adjustable physicochemical characteristics. This review explores the intersection of gelatin and its derivatives with fabrication techniques, offering a comprehensive examination of their synergistic potential in creating ELSs for various applications in biomedicine. It offers a deep dive into gelatin, including its structures and production, sources, processing, and properties. Additionally, the review explores various fabrication techniques employing gelatin and its derivatives, including generic fabrication techniques, microfluidics, and various 3D printing methods. Furthermore, it discusses the applications of ELSs based on gelatin in regenerative engineering as well as in cell therapies, bioadhesives, biorobots, and biosensors. Future directions and challenges in gelatin fabrication are also examined, highlighting emerging trends and potential areas for improvements and innovations. In summary, this comprehensive review underscores the significance of gelatin‐based ELSs in advancing biomedical engineering and lays the groundwork for guiding future research and developments within the field.more » « less
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Animal models are commonly used for drug screening before clinical trials. However, developing these models is time-consuming, and the results obtained from these models may differ from clinical outcomes due to the differences between animals and humans. To this end, 3D bioprinting offers several advantages for drug screening, such as high reproducibility and improved throughput, in addition to the human cells that can be used to generate these models. Here, we report the development of an animal patient-derived in vitro breast cancer model for drug screening using digital light processing (DLP) bioprinting. These bioprinted models demonstrated good cytocompatibility and preserved phenotypes of the cells. DLP enabled rapid fabrication with blood vessel-like channels to replicate, to a good extent, the tumor microenvironment. Our findings suggested that the improved microenvironment, provided by vascular structures within the bioprinted models, played a crucial role in reducing the chemoresistance of drugs. In addition, the correlation of the in vitro and in vivo drug-screening results was preliminarily performed to evaluate the predictive feasibility of this bioprinted model, suggesting a potential strategy for the design of future drug-testing platforms.more » « less
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Abstract Biofabrication and biomedical manufacturing are inherently multidisciplinary, integrating living systems with advanced manufacturing to create functional products for applications spanning regenerative engineering and medicine, in vitro disease modeling, drug discovery, and medical devices. As these technologies develop, they are emerging as core enablers of next-generation healthcare and life-science innovation. In the United States (U.S.), rapid progress across fabrication processes, material systems, physics-based modeling, and translation-oriented strategies is expanding the achievable design space and accelerating movement from laboratory demonstrations toward clinical and commercial deployment. We introduce major U.S. research frontiers and highlight representative advances in this field that support applications including organoids and other microphysiological systems for in vitro testing, engineered tissue constructs for in vivo use, and medical devices and biohybrid platforms. We further provide an outlook on advancing robust, ethical biofabrication and biomedical manufacturing in the U.S. research ecosystem.more » « lessFree, publicly-accessible full text available July 1, 2027
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To mimic physiological microenvironments in organ-on-a-chip systems, physiologically relevant parameters are required to precisely access drug metabolism. Oxygen level is a critical microenvironmental parameter to maintain cellular or tissue functions and modulate their behaviors. Current organ-on-a-chip setups are oftentimes subjected to the ambient incubator oxygen level at 21%, which is higher than most if not all physiological oxygen concentrations. Additionally, the physiological oxygen level in each tissue is different ranging from 0.5 to 13%. Here, a closed-loop modular multiorgan-on-chips platform is developed to enable not only real-time monitoring of the oxygen levels but, more importantly, tight control of them in the range of 4 to 20% across each connected microtissue-on-a-chip in the circulatory culture medium. This platform, which consists of microfluidic oxygen scavenger(s), an oxygen generator, a monitoring/controller system, and bioreactor(s), allows for independent, precise upregulation and downregulation of dissolved oxygen in the perfused culture medium to meet the physiological oxygen level in each modular microtissue compartment, as needed. Furthermore, drug studies using the platform demonstrate that the oxygen level affects drug metabolism in the parallelly connected liver, kidney, and arterial vessel microtissues without organ–organ interactions factored in. Overall, this platform can promote the performances of organ-on-a-chip devices in drug screening by providing more physiologically relevant and independently adjustable oxygen microenvironments for desired organ types on a single- or a multiorgan-on-chip(s) configuration.more » « less
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