Microfluidics for Drug Development: From Synthesis to Evaluation

Liu, Yuxiao; Sun, Lingyu; Zhang, Hui; Shang, Luoran; Zhao, Yuanjin

doi:10.1021/acs.chemrev.0c01289

Cited by 119 publications

(100 citation statements)

References 537 publications

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“…Compared with other fabrication strategies, there are several advantageous characteristics of the combination of hydrogels and microfluidic technology, such as single‐cell encapsulation, high drug‐loading efficiency, and controllable mechanical properties. [ 10 ] In this section, several typical biomedical applications of microfluidics‐mediated hydrogels, that is, drug encapsulation, cell encapsulation, and tissue engineering, are presented. In this context, hydrogels for cell encapsulation refer to loading individual or multiple cells into hydrogels that act as an extracellular matrix to ensure the exchange of nutrients and waste, therefore prolonging cell viability and enhancing the efficiency of cell therapy.…”

Section: Biomedical Applications Of Microfluidics‐mediated Micrometer...mentioning

confidence: 99%

“…[ 9 ] Additionally, the emergence of new fabrication techniques such as electrohydrodynamic spraying or electrospinning also promotes the development of micrometer‐sized hydrogels, which exhibits advantages of simplicity and cost‐effectiveness over batch emulsification and bulk mixing. [ 10 ] However, these techniques are not without shortcomings, such as the harsh fabrication process and the challenge of reproducible fabrication of micrometer‐sized hydrogel with finely controlled physicochemical properties. Microfluidic technology holds great potential as a promising tool to overcome these shortcomings, based on its high level of control over fluids in the micrometer range.…”

Section: Introductionmentioning

confidence: 99%

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Microfluidics Fabrication of Micrometer‐Sized Hydrogels with Precisely Controlled Geometries for Biomedical Applications

Wei

Wang

Hirvonen

et al. 2022

Adv Healthcare Materials

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Micrometer‐sized hydrogels are cross‐linked three‐dimensional network matrices with high‐water contents and dimensions ranging from several to hundreds of micrometers. Due to their excellent biocompatibility and capability to mimic physiological microenvironments in vivo, micrometer‐sized hydrogels have attracted much attention in the biomedical engineering field. Their biological properties and applications are primarily influenced by their chemical compositions and geometries. However, inhomogeneous morphologies and uncontrollable geometries limit traditional micrometer‐sized hydrogels obtained by bulk mixing. In contrast, microfluidic technology holds great potential for the fabrication of micrometer‐sized hydrogels since their geometries, sizes, structures, compositions, and physicochemical properties can be precisely manipulated on demand based on the excellent control over fluids. Therefore, micrometer‐sized hydrogels fabricated by microfluidic technology have been applied in the biomedical field, including drug encapsulation, cell encapsulation, and tissue engineering. This review introduces micrometer‐sized hydrogels with various geometries synthesized by different microfluidic devices, highlighting their advantages in various biomedical applications over those from traditional approaches. Overall, emerging microfluidic technologies enrich the geometries and morphologies of hydrogels and accelerate translation for industrial production and clinical applications.

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Section: Biomedical Applications Of Microfluidics‐mediated Micrometer...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microfluidics Fabrication of Micrometer‐Sized Hydrogels with Precisely Controlled Geometries for Biomedical Applications

Wei

Wang

Hirvonen

et al. 2022

Adv Healthcare Materials

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show abstract

“…However, the preparation of the MPRs with more complex interface characteristics and higher biocompatibility to comply with the needs of clinical and theoretical research remains challenging with the advancement of biomedical research. [174][175][176][177]…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

Microfluidic Particle Reactors: From Interface Characteristics to Cells and Drugs Related Biomedical Applications

Xin

et al. 2022

Adv Materials Inter

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with advanced functions, [6] can be attributed to two aspects. 1) The exquisite control and manipulation abilities of fluids at a microscale have reached a new height as droplet microfluidic technology is leaping forward. The precisely tunable interface characteristics of emulsion templates, determined by the optimization of fluids composition and interfacial complexity, contribute to the inherent interface properties of MPRs. [7][8][9][10] 2) The introduction of advanced materials expands the interface characteristics of the MPRs. Considerable natural polymers, synthetic polymers, and stimuli-responsive biomaterials have been employed continuously with the development of materials science. As a result, a series of performances possessed by the materials can significantly improve the inherent interface characteristics of the MPRs under a combination of the mentioned advanced materials. [11][12][13][14][15][16] Overall, researchers have stressed the improvement of the development process of interface characteristics and functions (such as substance encapsulation and controlled release) by providing novel technical innovations in every aspect to support biomedical clinical applications related to cells and drugs. Recently, the types, preparation methods, and biomedical applications of MPRs have been systematically presented in several excellent reviews. [3][4][5][8][9][10][17][18][19][20] The thermodynamic properties of liquid-liquid droplet reactors have been analyzed more specifically in some reviews. [7,17] However, the origin of interface characteristics of MPRs, as well as the function and cuttingedge cell-and drug-related biomedical applications determined by the interface characteristics, are deficient in a systematic summary. This review highlights that different emulsion templates endow the inherent interface characteristics of MPRs. Besides, the methods of converting emulsion templates into MPRs are summarized by introducing specific functional biomaterials, followed by the flexible and adjustable interface characteristics expanded by the mentioned materials. Moreover, the biomedical applications related to cells and drugs are analyzed based on the mentioned unique interface characteristics of the MPRs. Furthermore, the existing challenges regarding the current status are presented, and the subsequent development of the MPRs is illustrated from various perspectives (Scheme 1).

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“…Nevertheless, traditional digital microfluidics platforms can only perform multiplex or parallel biochemical reactions due to the use of a small number of droplets (from several up to tens) [27]. In addition, traditional digital microfluidics platforms have not been leveraged for 3D cell culture with continuous perfusion [28]. Therefore, the development of an advanced digital organ-on-a-chip platform with good parallelism, simple preparation and operation would be a significant step in the screening of anticancer drugs and toxicity testing, enabling a more efficient drug screening pipeline for liver cancer.…”

Section: Introductionmentioning

confidence: 99%

Development of digital organ-on-a-chip to assess hepatotoxicity and extracellular vesicle-based anti-liver cancer immunotherapy

Shi

et al. 2022

Bio-des. Manuf.

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Organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic agents. However, current organ-on-a-chip platforms are limited by a “single pot” design, which inevitably requires holistic analysis and limits parallel processing. Here, we developed a digital organ-on-a-chip by combining a microwell array with cellular microspheres, which significantly increased the parallelism over traditional organ-on-a-chip for drug development. Up to 127 uniform liver cancer microspheres in this digital organ-on-a-chip format served as individual analytical units, allowing for analysis with high consistency and quick response. Our platform displayed evident anti-cancer efficacy at a concentration of 10 μM for sorafenib, and had greater alignment than the “single pot” organ-on-a-chip with a previous in vivo study. In addition, this digital organ-on-a-chip demonstrated the treatment efficacy of natural killer cell-derived extracellular vesicles for liver cancer at 50 μg/mL. The successful development of this digital organ-on-a-chip platform provides high-parallelism and a low-variability analytical tool for toxicity assessment and the exploration of new anticancer modalities, thereby accelerating the joint endeavor to combat cancer. Graphic abstract

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Microfluidics for Drug Development: From Synthesis to Evaluation

Cited by 119 publications

References 537 publications

Microfluidics Fabrication of Micrometer‐Sized Hydrogels with Precisely Controlled Geometries for Biomedical Applications

Microfluidics Fabrication of Micrometer‐Sized Hydrogels with Precisely Controlled Geometries for Biomedical Applications

Microfluidic Particle Reactors: From Interface Characteristics to Cells and Drugs Related Biomedical Applications

Development of digital organ-on-a-chip to assess hepatotoxicity and extracellular vesicle-based anti-liver cancer immunotherapy

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