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Photo‐rheological properties of the a) Emul and b) Non‐Emul hydrogels (close symbol: G′; open symbol: G″). c) Gelation time of the Emul and Non‐Emul hydrogels. d) Representative images of the hydrogels cast by Emul and Non‐Emul photoresins. Scale bars: 3 mm. e) Stress‐strain curve and f) Young's modulus of the Emul and Non‐Emul hydrogels (close symbol: Emul photoresins; open symbol: Non‐Emul photoresins). g) Representative 3D reconstructed confocal images of FITC‐dextran perfused microgel‐based hydrogels. Scale bars: 60 µm. h) Representative confocal images of FITC‐dextran perfused bulk and microgel‐based hydrogels. Scale bars: 200 µm. i) Porosity of the microgel‐based hydrogels determined by the area occupied by the FITC‐dextran within the voids in 60 µm thick stacks. The data were collected from the confocal images. (n > 3)
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Microgel assembly as void‐forming bioinks in 3D bioprinting has evidenced recent success with a highlighted scaffolding performance of these bottom‐up biomaterial systems in supporting the viability and function of the laden cells. Here, a ternary‐component aqueous emulsion is established as a one‐step strategy to integrate the methacrylated gelati...
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Granular biomaterials have found widespread applications in tissue engineering, in part because of their inherent porosity, tunable properties, injectability, and 3D printability. However, the assembly of granular hydrogels typically relies on spherical microparticles and more complex particle geometries have been limited in scope, often requiring...
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... Consequently, using the biphasic nature of ATPS system bioinks to generate microgels has emerged as a promising strategy for refining material properties in bioprinting applications. 3,22 2.1. ATPS-derived microgel bioinks ATPS-derived microgel bioinks are built upon the foundational principles of ATPS by introducing microscale structuring to enhance material properties and functionality. ...
... Among the available fabrication methods, the batch emulsion process is widely used due to its simplicity, scalability, and compatibility with diverse polymer systems. 3,22 This method involves the mechanical mixing of two immiscible aqueous phases to generate dropletstabilized emulsions, which act as templates for microporous hydrogel formation. During the batch emulsion process, polymers such as GelMA, PEO, or dextran are phaseseparated into droplets within a continuous aqueous phase. ...
... 60 In Pickering emulsions, solid particles stabilize ATPS droplets by forming a protective layer at the interface that prevents coalescence and enhances stability. 3 Unlike conventional surfactant-stabilized emulsions, this method relies on colloidal stabilizers, such as silica nanoparticles or protein-based stabilizers, which absorb at the droplet interface to create a physical barrier. This method enables the formation of highly stable microgels with controlled size and extended stability, making it particularly effective for low interfacial tension systems like PEG-dextran ATPS. ...
Biological tissues possess intricate hierarchical structures that enable diverse cellular functions, which are critical for maintaining physiological processes. Mimicking these properties is central to advancing tissue engineering and regenerative medicine. Aqueous two-phase systems (ATPS)-derived microgel bioinks have emerged as a versatile platform, offering biocompatibility, mechanical tunability, and multifunctionality for bioprinting applications. Recent advancements, such as oxygen-releasing constructs and modular designs, have demonstrated the potential of ATPS-derived microgel bioinks to create tailored cellular microenvironments, addressing challenges like oxygen delivery and tissue-specific integration while replicating the complexities of native tissues. This review synthesizes these advancements, critically discussing key considerations, including material selection, physicochemical properties, mechanotransduction, and stress-relaxation behavior. Future directions include advancing multi-scale fabrication techniques, refining cell–material interactions, and addressing scalability challenges to bridge the gap between research and clinical application. By providing a comprehensive perspective on the state-of-the-art in ATPS-derived microgel bioinks, this review emphasizes their potential to transform bioprinting and tissue engineering.
... The printed auricular constructs have high elasticity, high printing accuracy, and low swelling ratio, which can mimic the microenvironment for cartilage regeneration. Wang et al. established a one-step strategy to integrate the GelMA microgel fabrication and assembly through vat photopolymerization in situ using DLP bioprinting [132]. Although bioprinting is appealing for building tissue mimics, precise positioning control of mini-tissue blocks (i.e., spheroids) in 3D space remains challenging. ...
Three-dimensional (3D) bioprinting has emerged as a groundbreaking technology for fabricating intricate and functional tissue constructs. Central to this technology are the bioinks, which provide structural support and mimic the extracellular environment, which is crucial for cellular executive function. This review summarizes the latest developments in microparticulate inks for 3D bioprinting and presents their inherent challenges. We categorize micro-particulate materials, including polymeric microparticles, tissue-derived microparticles, and bioactive inorganic microparticles, and introduce the microparticle ink formulations, including granular microparticles inks consisting of densely packed microparticles and composite microparticle inks comprising microparticles and interstitial matrix. The formulations of these microparticle inks are also delved into highlighting their capabilities as modular entities in 3D bioprinting. Finally, existing challenges and prospective research trajectories for advancing the design of microparticle inks for bioprinting are discussed.
Bioprinting incorporates printable biomaterials into 3D printing to create intricate tissues that maintain a defined 3D structure while supporting the survival and function of relevant cell types. A major challenge in 3D bioprinting is tuning material properties to ensure compatibility with different types of cells, while accurately mimicking the physiological microenvironment. Developing novel bioinks tailored to specific applications can help address this challenge by combining various materials and additives to tune the bioink formulation. Microspheres - small spherical particles - can incorporate drugs or growth factors to enable their controlled release, encapsulate cells to provide protection during printing, and provide structural reinforcement to tune mechanical properties and enable complex architectures. The particles range in size from 1 to 1000 μm and can be tuned to meet desired functions by optimizing their mode of production and the materials used for fabrication. This review presents an overview of microsphere production methods and considerations for optimizing the production process. It then summarizes how microspheres have been used to date in bioprinting applications. Finally, the existing challenges associated with the creation and use of microspheres are discussed along with avenues for future research.
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