Engineered cell-laden alginate microparticles for 3D culture

Author(s):  
Bumseok Namgung ◽  
Kalpana Ravi ◽  
Pooja Prathyushaa Vikraman ◽  
Shiladitya Sengupta ◽  
Hae Lin Jang

Advanced microfabrication technologies and biocompatible hydrogel materials facilitate the modeling of 3D tissue microenvironment. Encapsulation of cells in hydrogel microparticles offers an excellent high-throughput platform for investigating multicellular interaction with their surrounding microenvironment. Compartmentalized microparticles support formation of various unique cellular structures. Alginate has emerged as one of the most dominant hydrogel materials for cell encapsulation owing to its cytocompatibility, ease of gelation, and biocompatibility. Alginate hydrogel provides a permeable physical boundary to the encapsulated cells and develops an easily manageable 3D cellular structure. The interior structure of alginate hydrogel can further regulate the spatiotemporal distribution of the embedded cells. This review provides a specific overview of the representative engineering approaches to generate various structures of cell-laden alginate microparticles in a uniform and reproducible manner. Capillary nozzle systems, microfluidic droplet systems, and non-chip based high-throughput microfluidic systems are highlighted for developing well-regulated cellular structure in alginate microparticles to realize potential drug screening platform and cell-based therapy. We conclude with the discussion of current limitations and future directions for realizing the translation of this technology to the clinic.

2020 ◽  
Vol 9 (1) ◽  
pp. 60-66
Author(s):  
Trung Dang Cu ◽  
Phuong Le Ha ◽  
Hong Hoang Thu ◽  
Mai Mac Thi Thu ◽  
Vu Tran Khac ◽  
...  

Alginate-based hydrogels are attracted much attention in biomedical and chemical field, and their size and shape are significant to their applications like drug delivery and cell encapsulation. Monodisperse sodium alginate microdroplets are produced using a flow-focusing microfluidic device (MFFD) by adjusting the flow rate on the continuous phase (soybean oil) and the dispersed phase (sodium alginate solution). The external gelation process of sodium alginate microdroplets occurs outside the chanel in a calcium chloride solution to form calcium alginate hydrogel particales. The shape, size and size distribution of these calcium alginate hydrogel particles depend strongly on the flow rate inside the MFFD. By optimizing the parameters, the hydrogel microparticles were obtained with diameters ranging from 70 µm to 100 µm with size distribution under 10%, depending on experimental conditions. The removal of Cu2+ ions by the absorption of hydrogel microparticles was also demonstrated.


ACS Nano ◽  
2021 ◽  
Author(s):  
Sneh M. Toprani ◽  
Dimitrios Bitounis ◽  
Qiansheng Huang ◽  
Nathalia Oliveira ◽  
Kee Woei Ng ◽  
...  

ACS Sensors ◽  
2020 ◽  
Author(s):  
Ke-Jia Wu ◽  
Chun Wu ◽  
Feng Chen ◽  
Sha-Sha Cheng ◽  
Dik-Lung Ma ◽  
...  

2016 ◽  
Vol 60 (10) ◽  
pp. 5995-6002 ◽  
Author(s):  
Kristin R. Baker ◽  
Bimal Jana ◽  
Henrik Franzyk ◽  
Luca Guardabassi

ABSTRACTThe envelope of Gram-negative bacteria constitutes an impenetrable barrier to numerous classes of antimicrobials. This intrinsic resistance, coupled with acquired multidrug resistance, has drastically limited the treatment options against Gram-negative pathogens. The aim of the present study was to develop and validate an assay for identifying compounds that increase envelope permeability, thereby conferring antimicrobial susceptibility by weakening of the cell envelope barrier in Gram-negative bacteria. A high-throughput whole-cell screening platform was developed to measureEscherichia colienvelope permeability to a β-galactosidase chromogenic substrate. The signal produced by cytoplasmic β-galactosidase-dependent cleavage of the chromogenic substrate was used to determine the degree of envelope permeabilization. The assay was optimized by using known envelope-permeabilizing compounds andE. coligene deletion mutants with impaired envelope integrity. As a proof of concept, a compound library comprising 36 peptides and 45 peptidomimetics was screened, leading to identification of two peptides that substantially increased envelope permeability. Compound 79 reduced significantly (from 8- to 125-fold) the MICs of erythromycin, fusidic acid, novobiocin and rifampin and displayed synergy (fractional inhibitory concentration index, <0.2) with these antibiotics by checkerboard assays in two genetically distinctE. colistrains, including the high-risk multidrug-resistant, CTX-M-15-producing sequence type 131 clone. Notably, in the presence of 0.25 μM of this peptide, both strains were susceptible to rifampin according to the resistance breakpoints (R> 0.5 μg/ml) for Gram-positive bacterial pathogens. The high-throughput screening platform developed in this study can be applied to accelerate the discovery of antimicrobial helper drug candidates and targets that enhance the delivery of existing antibiotics by impairing envelope integrity in Gram-negative bacteria.


2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Cheng Zhang ◽  
Romain Grossier ◽  
Nadine Candoni ◽  
Stéphane Veesler

AbstractThis review examines the preparation of alginate hydrogel microparticles by using droplet-based microfluidics, a technique widely employed for its ease of use and excellent control of physicochemical properties, with narrow size distribution. The gelation of alginate is realized “on-chip” and/or “off-chip”, depending on where cross-linkers are introduced. Various strategies are described and compared. Microparticle properties such as size, shape, concentration, stability and mechanical properties are discussed. Finally, we consider future perspectives for the preparation of hydrogel microparticles and their potential applications.


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