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      Microfluidic fabrication of microparticles for biomedical applications

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          Abstract

          Droplet microfluidics offers exquisite control over the flows of multiple fluids in microscale, enabling fabrication of advanced microparticles with precisely tunable structures and compositions in a high throughput manner. The combination of these remarkable features with proper materials and fabrication methods has enabled high efficiency, direct encapsulation of actives in microparticles whose features and functionalities can be well controlled. These microparticles have great potential in a wide range of bio-related applications including drug delivery, cell-laden matrices, biosensors and even as artificial cells. In this review, we briefly summarize the materials, fabrication methods, and microparticle structures produced with droplet microfluidics. We also provide a comprehensive overview of their recent uses in biomedical applications. Finally, we discuss the existing challenges and perspectives to promote the future development of these engineered microparticles.

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          Most cited references259

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          Designing hydrogels for controlled drug delivery

          Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
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            Monodisperse double emulsions generated from a microcapillary device.

            Double emulsions are highly structured fluids consisting of emulsion drops that contain smaller droplets inside. Although double emulsions are potentially of commercial value, traditional fabrication by means of two emulsification steps leads to very ill-controlled structuring. Using a microcapillary device, we fabricated double emulsions that contained a single internal droplet in a core-shell geometry. We show that the droplet size can be quantitatively predicted from the flow profiles of the fluids. The double emulsions were used to generate encapsulation structures by manipulating the properties of the fluid that makes up the shell. The high degree of control afforded by this method and the completely separate fluid streams make this a flexible and promising technique.
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              Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up.

              This article describes the process of formation of droplets and bubbles in microfluidic T-junction geometries. At low capillary numbers break-up is not dominated by shear stresses: experimental results support the assertion that the dominant contribution to the dynamics of break-up arises from the pressure drop across the emerging droplet or bubble. This pressure drop results from the high resistance to flow of the continuous (carrier) fluid in the thin films that separate the droplet from the walls of the microchannel when the droplet fills almost the entire cross-section of the channel. A simple scaling relation, based on this assertion, predicts the size of droplets and bubbles produced in the T-junctions over a range of rates of flow of the two immiscible phases, the viscosity of the continuous phase, the interfacial tension, and the geometrical dimensions of the device.
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                Author and article information

                Journal
                0335405
                29764
                Chem Soc Rev
                Chem Soc Rev
                Chemical Society reviews
                0306-0012
                1460-4744
                6 August 2018
                30 July 2018
                30 July 2019
                : 47
                : 15
                : 5646-5683
                Affiliations
                [a ]School of Engineering and Applied Sciences, Department of Physics, Harvard University, 29 Oxford Street, Cambridge, MA 02138, USA.
                [b ]School of Materials Science & Engineering, Department of Polymer Materials, Shanghai University, 333 Nanchen Street, Shanghai 200444, China.
                [c ]The State Key Laboratory of Chemical Engineering, Tsinghua University, Gongwuguan 772, Haidian District, Beijing 100084, China.
                [d ]State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
                [e ]Division of Cosmetic Science and Technology, Daegu Haany University, Gyeongsan, Gyeongbuk 38610, Republic of Korea.
                [f ]Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Republic of Korea.
                Author notes
                Article
                PMC6140344 PMC6140344 6140344 nihpa981114
                10.1039/c7cs00263g
                6140344
                29999050
                deb006e9-af2c-486f-acfc-b8ec64e180d8
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