Biopolymer Microparticles Prepared by Microfluidics for Biomedical Applications

Jo, Young-Woo; Lee, Daeyeon

doi:10.1002/smll.201903736

Cited by 98 publications

(76 citation statements)

References 227 publications

(287 reference statements)

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“…Microgels are solvent-swollen macromolecular networks forming finite structures ranging in size from tens of micrometers to the nanometer scale [ 1 ]. Due to their unique versatility regarding the adjustment of mechanical and physicochemical properties, microgels have attracted attention as promising substrates, e.g., for engineered extracellular matrices (ECMs) [ 2 , 3 ] drug delivery systems [ 4 , 5 , 6 ], or cell-free biosynthesis environments [ 7 , 8 , 9 ]. Compared to bulk gels, the higher surface-to-volume ratio of microgel particles results in a remarkably enhanced molecular mass transport between the polymer network and the surrounding (micro-)environment [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties

et al. 2020

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The demand for tailored, micrometer-scaled biomaterials in cell biology and (cell-free) biotechnology has led to the development of tunable microgel systems based on natural polymers, such as hyaluronic acid (HA). To precisely tailor their physicochemical and mechanical properties and thus to address the need for well-defined microgel systems, in this study, a bottom-up material guide is presented that highlights the synergy between highly selective bio-orthogonal click chemistry strategies and the versatility of a droplet microfluidics (MF)-assisted microgel design. By employing MF, microgels based on modified HA-derivates and homobifunctional poly(ethylene glycol) (PEG)-crosslinkers are prepared via three different types of click reaction: Diels–Alder [4 + 2] cycloaddition, strain-promoted azide-alkyne cycloaddition (SPAAC), and UV-initiated thiol–ene reaction. First, chemical modification strategies of HA are screened in-depth. Beyond the microfluidic processing of HA-derivates yielding monodisperse microgels, in an analytical study, we show that their physicochemical and mechanical properties—e.g., permeability, (thermo)stability, and elasticity—can be systematically adapted with respect to the type of click reaction and PEG-crosslinker concentration. In addition, we highlight the versatility of our HA-microgel design by preparing non-spherical microgels and introduce, for the first time, a selective, hetero-trifunctional HA-based microgel system with multiple binding sites. As a result, a holistic material guide is provided to tailor fundamental properties of HA-microgels for their potential application in cell biology and (cell-free) biotechnology.

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Section: Introductionmentioning

confidence: 99%

Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties

et al. 2020

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“…After irradiating for 4 min at a laser intensity of 0.7 W cm −2 , the temperature of Mg@PLGA microspheres and nanospheres with Mg concentration of 60 mg mL −1 increases from 25 °C to 40 °C, which is sufficient for photothermal therapy (Figure 3b,e). [ 3,10,15–43 ] After irradiating for 10 min, the temperature of both spheres increases from 25 °C to 55 °C. Both the rising and declining of temperature in response to laser switching on and off are prompt and identical; moreover, the photothermal response of Mg@PLGA microspheres and nanospheres are reliable for multiple repeated cycles with laser on‐and‐off (Figure 3c,f).…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, bottom‐up fabrication such as microfluidic emulsification produces uniform microsized carriers with exquisite control over size, size distribution, and encapsulation efficiency. [ 32–34 ] As such, the affirmative relationship between the characteristic and function of uniform polymer carriers can be achieved. [ 19,35 ] For instance, larger microparticles with shell layers shows significantly reduced burst release and sustained accumulative release profile.…”

Section: Introductionmentioning

confidence: 99%

Micro‐/Nano‐Structures on Biodegradable Magnesium@PLGA and Their Cytotoxicity, Photothermal, and Anti‐Tumor Effects

et al. 2020

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The size and structural control of particulate carriers for imaging agents and therapeutics are constant themes in designing smart delivery systems. This is motivated by the causal relationship between geometric parameters and functionalities of delivery vehicles. Here, both in vitro and in vivo, the controlling factors for cytotoxicity, photothermal, and anti‐tumor effects of biodegradable magnesium@poly(lactic‐co‐glycolic acid (Mg@PLGA) particulate carriers with different sizes and shell thicknesses are investigated. Mg@PLGA microspheres fabricated by microfluidic emulsification are shown to have higher Mg encapsulation efficiency, 87%, than nanospheres by ultrasonic homogenization, 50%. The photothermal and anti‐tumor effects of Mg@PLGA spheres are found to be dictated by their Mg content, irrelevant to size and structural features, as demonstrated in both in vitro cell assays and in vivo mice models. These results also provide important implications for designing and fabricating stimuli‐responsive drug delivery vehicles.

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Section: Drug Delivery Systems and Droplet‐based Technologymentioning

confidence: 99%

Droplet Microfluidics for Tumor Drug‐Related Studies and Programmable Artificial Cells

Dimitriou

Tornillo

et al. 2021

Global Challenges

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(1 of 17)www.global-challenges.com robotics, have promoted the use of in vitro tumor models in high-throughput drug screenings. [2,3] High-throughput screens for anticancer drugs have been, for a long time, limited to 2D culture of tumor cells, grown as a monolayer on the bottom of a well of a microtiter plate. Compared to 2D cell cultures, 3D culture systems can more faithfully model cell-cell interactions, matrix deposition and tumor microenvironments, including more physiological flow conditions, oxygen and nutrient gradients. [4] Therefore, 3D cultures have recently begun to be incorporated into high-throughput drug screenings, with the aim of better predicting drug efficacy and improving the prioritization of candidate drugs for further in vivo testing in animals.Because of the relatively simple, reproducible, amenable to automation and scalable culture methods, single-cell type and mixed-cell tumor spheroids, known as multicellular tumor spheroids (MCTSs), are used as 3D models. [5] There exists a broad range of natural hydrogels that are compatible with microfluidics, and which provide cancer cells with mechanical cues and adhesion sites to proliferate and grow into MCTSs. [6] With the aid of microfluidics and development of more complex 3D tumor models, [7,8] and the large-scale production of tumor spheroids in hydrogels, the number of compounds that could progress to in vivo testing could be restricted, thus reducing the number of animals needed for preclinical studies.Tumor-targeted drug delivery using microparticles and liposomes is beneficial compared to conventional drug administration. This is because encapsulated drug dosages can be controlled, healthy tissues can remain unharmed during treatment and drug resistance of cancer cells may be reduced/ prevented. [9,10] Microparticles and liposomes can be tailored to specifically target tumor sites using molecular conjugates, while avoiding toxic effects. [9] This review discusses the application of droplet-based microfluidic technologies for the development of accurate in vitro tumor models and improved cancer treatment strategies. The first part of the review centers around the generation of MCTSs in natural hydrogels for a better recapitulation of the in vivo tumor microenvironment. The second section is focused on microparticle and liposomal production for tumor-targeted drug delivery. Emphases is given to microfluidic methodologies for the production of these systems, and the potential of compartmentalized artificial cells as anticancer drug screening platforms.

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Biopolymer Microparticles Prepared by Microfluidics for Biomedical Applications

Cited by 98 publications

References 227 publications

Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties

Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties

Micro‐/Nano‐Structures on Biodegradable Magnesium@PLGA and Their Cytotoxicity, Photothermal, and Anti‐Tumor Effects

Droplet Microfluidics for Tumor Drug‐Related Studies and Programmable Artificial Cells

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