Design of an Adhesive Film-Based Microfluidic Device for Alginate Hydrogel-Based Cell Encapsulation

Enck, Kevin; Rajan, Shiny Priya; Aleman, Julio; Castagno, Simone; Long, Emily; Khalil, Fatma; Hall, Adam R.; Opara, Emmanuel C.

doi:10.1007/s10439-020-02453-9

Cited by 20 publications

(12 citation statements)

References 64 publications

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“…Then surface modification was carried out by alginate hydrogel coat to improve its biocompatibility. Alginate has been widely used in cell micro‐encapsulation for the 3D scaffold model 26–28 . Amenable physical characteristics, pleasant biological properties, and remarkable high similarity to the soft tissue mechanical property make alginate an excellent biomaterial for tissue engineering and drug delivery 29–33 …”

Section: Discussionmentioning

confidence: 99%

Surface modification of neurotrophin‐3 loaded PCL/chitosan nanofiber/net by alginate hydrogel microlayer for enhanced biocompatibility in neural tissue engineering

Habibizadeh

Nadri

Fattahi

et al. 2021

J Biomedical Materials Res

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This study prepared a novel three‐dimensional nanocomposite scaffold by the surface modification of PCL/chitosan nanofiber/net with alginate hydrogel microlayer, hoping to have the privilege of both nanofibers and hydrogels simultaneously. Bead free randomly oriented nanofiber/net (NFN) structure composed of chitosan and polycaprolactone (PCL) was fabricated by electrospinning method. The low surface roughness, good hydrophilicity, and high porosity were obtained from the NFN structure. Then, the PCL/chitosan nanofiber/net was coated with a microlayer of alginate containing neurotrophin‐3 (NT‐3) and conjunctiva mesenchymal stem cells (CJMSCs) as a new stem cell source. According to the cross‐sectional FESEM, the scaffold shows a two‐layer structure with interconnected pores in the range of 20 μm diameter. The finding revealed that the surface modification of nanofiber/net by alginate hydrogel microlayer caused lower inflammatory response and higher proliferation of CJMSCs than the unmodified scaffold. The initial burst release of NT‐3 was 69% in 3 days which followed by a sustained release up to 21 days. The RT‐PCR analysis showed that the expression of Nestin, MAP‐2, and β‐tubulin III genes were increased 6, 5.4, and 8.8‐fold, respectively. The results revealed that the surface‐modified biomimetic scaffold possesses enhanced biocompatibility and could successfully differentiate CJMSCs to the neuron‐like cells.

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Section: Discussionmentioning

confidence: 99%

Surface modification of neurotrophin‐3 loaded PCL/chitosan nanofiber/net by alginate hydrogel microlayer for enhanced biocompatibility in neural tissue engineering

Habibizadeh

Nadri

Fattahi

et al. 2021

J Biomedical Materials Res

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“…Here, the dispersed phase is an aqueous solution of charged polymer containing an undissociated calcium or barium compound (shown as solid black circles in Figure 1 ), such as CaCO 3 , BaCO 3 [ 27 ], tricalcium citrate [ 28 ], and Ca-EDTA [ 29 ].…”

Section: Microfluidic Production Of Spherical Matrix-type Microgelsmentioning

confidence: 99%

Crosslinking Strategies for the Microfluidic Production of Microgels

2021

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This article provides a systematic review of the crosslinking strategies used to produce microgel particles in microfluidic chips. Various ionic crosslinking methods for the gelation of charged polymers are discussed, including external gelation via crosslinkers dissolved or dispersed in the oil phase; internal gelation methods using crosslinkers added to the dispersed phase in their non-active forms, such as chelating agents, photo-acid generators, sparingly soluble or slowly hydrolyzing compounds, and methods involving competitive ligand exchange; rapid mixing of polymer and crosslinking streams; and merging polymer and crosslinker droplets. Covalent crosslinking methods using enzymatic oxidation of modified biopolymers, photo-polymerization of crosslinkable monomers or polymers, and thiol-ene “click” reactions are also discussed, as well as methods based on the sol−gel transitions of stimuli responsive polymers triggered by pH or temperature change. In addition to homogeneous microgel particles, the production of structurally heterogeneous particles such as composite hydrogel particles entrapping droplet interface bilayers, core−shell particles, organoids, and Janus particles are also discussed. Microfluidics offers the ability to precisely tune the chemical composition, size, shape, surface morphology, and internal structure of microgels by bringing multiple fluid streams in contact in a highly controlled fashion using versatile channel geometries and flow configurations, and allowing for controlled crosslinking.

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“…[47] Single cell and multiple cell encapsulation protocols have been established using microfluidics and hydrogels, in order to investigate single cell behavior within a designated ECM, and to study cell-cell and cell-ECM interactions, respectively. [48,49] The application of microfluidics allows for experimental flexibility and agility as well as targeted and minimized resource consumption, which is of considerable benefit to cancer research, since the costs of drugs and reagents demand high precision. [50] Entrapped cells in a confined environment, such as within hydrogel beads produced using microfluidic technology, can be analyzed on or off-chip.…”

Section: Cell Encapsulation Using Droplet-based Microfluidicsmentioning

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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Design of an Adhesive Film-Based Microfluidic Device for Alginate Hydrogel-Based Cell Encapsulation

Cited by 20 publications

References 64 publications

Surface modification of neurotrophin‐3 loaded PCL/chitosan nanofiber/net by alginate hydrogel microlayer for enhanced biocompatibility in neural tissue engineering

Surface modification of neurotrophin‐3 loaded PCL/chitosan nanofiber/net by alginate hydrogel microlayer for enhanced biocompatibility in neural tissue engineering

Crosslinking Strategies for the Microfluidic Production of Microgels

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

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