scholarly journals The Combined Effects of Co-Culture and Substrate Mechanics on 3D Tumor Spheroid Formation within Microgels Prepared via Flow-Focusing Microfluidic Fabrication

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 229 ◽  
Author(s):  
Dongjin Lee ◽  
Chaenyung Cha
Keyword(s):  
Mechanical Properties ◽  
Cell Culture ◽  
Microfluidic Device ◽  
3D Cell Culture ◽  
Breast Adenocarcinoma ◽  
Adherent Cell ◽  
Flow Focusing ◽  
Spheroid Formation ◽  
3D Scaffold ◽  
Tumor Spheroids

Tumor spheroids are considered a valuable three dimensional (3D) tissue model to study various aspects of tumor physiology for biomedical applications such as tissue engineering and drug screening as well as basic scientific endeavors, as several cell types can efficiently form spheroids by themselves in both suspension and adherent cell cultures. However, it is more desirable to utilize a 3D scaffold with tunable properties to create more physiologically relevant tumor spheroids as well as optimize their formation. In this study, bioactive spherical microgels supporting 3D cell culture are fabricated by a flow-focusing microfluidic device. Uniform-sized aqueous droplets of gel precursor solution dispersed with cells generated by the microfluidic device are photocrosslinked to fabricate cell-laden microgels. Their mechanical properties are controlled by the concentration of gel-forming polymer. Using breast adenocarcinoma cells, MCF-7, the effect of mechanical properties of microgels on their proliferation and the eventual spheroid formation was explored. Furthermore, the tumor cells are co-cultured with macrophages of fibroblasts, which are known to play a prominent role in tumor physiology, within the microgels to explore their role in spheroid formation. Taken together, the results from this study provide the design strategy for creating tumor spheroids utilizing mechanically-tunable microgels as 3D cell culture platform.

scholarly journals Towards a scaled-up T cell-mediated cytotoxicity assay in 3D cell culture using microscopy

2019 ◽  
Author(s):  
Elinor Gottschalk ◽  
Eric Czech ◽  
Bulent Arman Aksoy ◽  
Pinar Aksoy ◽  
Jeff Hammerbacher
Keyword(s):  
Cell Culture ◽  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Three Dimensional ◽  
Collagen Gel ◽  
3D Cell Culture ◽  
3D Scaffold ◽  
Tumor Spheroids ◽  
Drug Induced

AbstractThree-dimensional (3D) cell culture systems with tumor spheroids are being adopted for research on the antitumor activity of drug treatments and cytotoxic T cells. Analysis of the cytotoxic effect on 3D tumor cultures within a 3D scaffold, such as collagen, is challenging. Image-based approaches often use confocal microscopy, which greatly limits the sample size of tumor spheroids that can be assayed. We explored a system where tumor spheroids growing in a collagen gel within a microfluidics chip can be treated with drugs or co-cultured with T cells. We attempted to adapt the system to measure the death of cells in the tumor spheroids directly in the microfluidics chip via automated widefield fluorescence microscopy. We were able to successfully measure drug-induced cytotoxicity in tumor spheroids, but had difficulties extending the system to measure T cell-mediated tumor killing.Abstract Figure

NanoPADs and nanoFACEs: an optically transparent nanopaper-based device for biomedical applications

Lab on a Chip ◽  
2020 ◽  
Vol 20 (18) ◽  
pp. 3322-3333
Author(s):  
Binbin Ying ◽  
Siwan Park ◽  
Longyan Chen ◽  
Xianke Dong ◽  
Edmond W. K. Young ◽  
...  
Keyword(s):  
Cell Culture ◽  
Microfluidic Device ◽  
Biomedical Applications ◽  
Adherent Cell ◽  
Optically Transparent ◽  
Adherent Cell Culture

A highly transparent nanopaper-based microfluidic device for chemical/biosensing and cell culture, which is branded as nanopaper-based analytical devices (nanoPADs) and nanofibrillated adherent cell-culture platforms (nanoFACEs).

scholarly journals Aspiration-mediated hydrogel micropatterning using rail-based open microfluidic devices for high-throughput 3D cell culture

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dohyun Park ◽  
Jungseub Lee ◽  
Younggyun Lee ◽  
Kyungmin Son ◽  
Jin Woo Choi ◽  
...  
Keyword(s):  
Cell Culture ◽  
Capillary Pressure ◽  
Microfluidic Device ◽  
High Throughput ◽  
3D Cell Culture ◽  
Microfluidic Devices ◽  
Cell Types ◽  
Human Organ ◽  
Patterning Technique ◽  
Experimental Yield

AbstractMicrofluidics offers promising methods for aligning cells in physiologically relevant configurations to recapitulate human organ functionality. Specifically, microstructures within microfluidic devices facilitate 3D cell culture by guiding hydrogel precursors containing cells. Conventional approaches utilize capillary forces of hydrogel precursors to guide fluid flow into desired areas of high wettability. These methods, however, require complicated fabrication processes and subtle loading protocols, thus limiting device throughput and experimental yield. Here, we present a swift and robust hydrogel patterning technique for 3D cell culture, where preloaded hydrogel solution in a microfluidic device is aspirated while only leaving a portion of the solution in desired channels. The device is designed such that differing critical capillary pressure conditions are established over the interfaces of the loaded hydrogel solution, which leads to controlled removal of the solution during aspiration. A proposed theoretical model of capillary pressure conditions provides physical insights to inform generalized design rules for device structures. We demonstrate formation of multiple, discontinuous hollow channels with a single aspiration. Then we test vasculogenic capacity of various cell types using a microfluidic device obtained by our technique to illustrate its capabilities as a viable micro-manufacturing scheme for high-throughput cellular co-culture.

scholarly journals A reliable and affordable 3D tumor spheroid model for natural product drug discovery: A case study of curcumin

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Loh Teng Hern Tan ◽  
Liang Ee Low ◽  
Siah Ying Tang ◽  
Wei Hsum Yap ◽  
Lay Hong Chuah ◽  
...  
Keyword(s):  
Cell Culture ◽  
Drug Discovery ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Automated Image Analysis ◽  
Tumor Spheroids ◽  
Culture Methods ◽  
In Vivo Models

Three-dimensional cell culture methods revolutionize the field of anticancer drug discovery, forming an important link-bridge between conventional in vitro and in vivo models and conferring significant clinical and biological relevant data. The current work presents an affordable yet reproducible method of generating homogenous 3D tumor spheroids. Also, a new open source software is adapted to perform an automated image analysis of 3D tumor spheroids and subsequently generate a list of morphological parameters of which could be utilized to determine the response of these spheroids toward treatments. Our data showed that this work could serve as a reliable 3D cell culture platform for preclinical cytotoxicity testing of natural products prior to the expensive and time-consuming animal models

Chitosan–polydopamine hydrogel complex: a novel green adhesion agent for reversibly bonding thermoplastic microdevice and its application for cell-friendly microfluidic 3D cell culture

Lab on a Chip ◽  
2020 ◽  
Vol 20 (19) ◽  
pp. 3524-3534
Author(s):  
Kieu The Loan Trinh ◽  
Nguyen Xuan Thanh Le ◽  
Nae Yoon Lee
Keyword(s):  
Cell Culture ◽  
3D Cell Culture ◽  
Spheroid Formation

A chitosan–polydopamine hydrogel complex was introduced as an UV-assisted biocompatible adhesion agent for fabricating a PMMA microdevice employed in spheroid formation.

Enzymatically crosslinked poly(2-alkyl-2-oxazoline) networks for 3D cell culture

2018 ◽  
Vol 6 (46) ◽  
pp. 7568-7572 ◽  
Author(s):  
Lucca Trachsel ◽  
Nicolas Broguiere ◽  
Jan-Georg Rosenboom ◽  
Marcy Zenobi-Wong ◽  
Edmondo M. Benetti
Keyword(s):  
Mechanical Properties ◽  
Cell Culture ◽  
Cell Viability ◽  
3D Cell Culture ◽  
High Cell ◽  
Tunable Mechanical Properties

Cellularized poly(2-alkyl-2-oxazoline) hydrogels fabricated by sortase-mediated crosslinking feature tunable mechanical properties and enable extremely high cell viability.

scholarly journals Influence of electrohydrodynamic jetting parameters on the morphology of PCL scaffolds

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Hang Liu ◽  
Sanjairaj Vijayavenkataraman ◽  
Dandan Wang ◽  
Linzhi Jing ◽  
Jie Sun ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Attachment ◽  
3D Cell Culture ◽  
Solution Concentration ◽  
Processing Parameters ◽  
Optical Microscope ◽  
3D Scaffold ◽  
Sem Images ◽  
Scaffold Fabrication ◽  
Fibre Characteristics

 One of the important constituents in tissue engineering is scaffold, which provides structural support and suitable microenvironment for the cell attachment, growth and proliferation. To fabricate micro/nano structures for soft tissue repair and three-dimensional (3D) cell culture, the key is to improve fibre-based scaffold fabrication. Electrohydrodynamic (EHD) jetting is capable of producing and orientating submicron fibres for 3D scaffold fabrication. In this work, an EHD-jetting system was developed to explore the relationship between vital processing parameters and fibre characteristics. In this study, polycaprolactone (PCL) solution prepared by dissolving PCL pellets in acetic acid was used to fabricate the scaffolds. The influence of voltage, motorized stage speed, solution feed rate, and solution concentration on fibre characteristics and scaffold pattern were studied. Morphology of the EHD-jetted PCL fibres and scaffolds were analysed using optical microscope images and scanning electron microscope (SEM) images. Multi-layer scaffolds with the varied coiled pattern were fabricated and analysed. Cell attachment and proliferation have to be investigated in the future by further cell culture studies on these multi-layer coiled scaffolds.

scholarly journals Microchip-based 3D-cell culture using polymer nanofibers generated by solution blow spinning

2017 ◽  
Vol 9 (22) ◽  
pp. 3274-3283 ◽  
Author(s):  
Chengpeng Chen ◽  
Alexandra D. Townsend ◽  
Scott A. Sell ◽  
R. Scott Martin
Keyword(s):  
Cell Culture ◽  
Microfluidic Device ◽  
3D Cell Culture ◽  
Polymer Nanofibers ◽  
3D Printed ◽  
Solution Blow Spinning

Fibers produced by solution blow spinning (with a 3D printed sheath device) were integrated into a microfluidic device for 3D cell culture.

Ultra-tough injectable cytocompatible hydrogel for 3D cell culture and cartilage repair

2018 ◽  
Vol 6 (9) ◽  
pp. 1351-1358 ◽  
Author(s):  
Yanran Zhao ◽  
Mengnan Li ◽  
Bingchuan Liu ◽  
Junfeng Xiang ◽  
Zhiyong Cui ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cell Culture ◽  
Cartilage Repair ◽  
High Performance ◽  
3D Cell Culture ◽  
Load Bearing ◽  
Tunable Mechanical Properties ◽  
And Cartilage

A high-performance hydrogel was synthesized by a facile dual dynamic crosslinking strategy that showed injectability, cytocompatibility, broadly tunable mechanical properties and the potential for repair of load-bearing tissues.

scholarly journals Viscoelastic Oxidized Alginates with Reversible Imine Type Crosslinks: Self-Healing, Injectable, and Bioprintable Hydrogels

Gels ◽  
2018 ◽  
Vol 4 (4) ◽  
pp. 85 ◽  
Author(s):  
Shahzad Hafeez ◽  
Huey Ooi ◽  
Francis Morgan ◽  
Carlos Mota ◽  
Monica Dettin ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cell Culture ◽  
Viscoelastic Properties ◽  
Soft Tissues ◽  
3D Cell Culture ◽  
Cell Delivery ◽  
Self Healing ◽  
Marked Influence ◽  
Cell Culture Systems ◽  
Multiscale Structures

Bioprinting techniques allow for the recreation of 3D tissue-like structures. By deposition of hydrogels combined with cells (bioinks) in a spatially controlled way, one can create complex and multiscale structures. Despite this promise, the ability to deposit customizable cell-laden structures for soft tissues is still limited. Traditionally, bioprinting relies on hydrogels comprised of covalent or mostly static crosslinks. Yet, soft tissues and the extracellular matrix (ECM) possess viscoelastic properties, which can be more appropriately mimicked with hydrogels containing reversible crosslinks. In this study, we have investigated aldehyde containing oxidized alginate (ox-alg), combined with different cross-linkers, to develop a small library of viscoelastic, self-healing, and bioprintable hydrogels. By using distinctly different imine-type dynamic covalent chemistries (DCvC), (oxime, semicarbazone, and hydrazone), rational tuning of rheological and mechanical properties was possible. While all materials showed biocompatibility, we observed that the nature of imine type crosslink had a marked influence on hydrogel stiffness, viscoelasticity, self-healing, cell morphology, and printability. The semicarbazone and hydrazone crosslinks were found to be viscoelastic, self-healing, and printable—without the need for additional Ca2+ crosslinking—while also promoting the adhesion and spreading of fibroblasts. In contrast, the oxime cross-linked gels were found to be mostly elastic and showed neither self-healing, suitable printability, nor fibroblast spreading. The semicarbazone and hydrazone gels hold great potential as dynamic 3D cell culture systems, for therapeutics and cell delivery, and a newer generation of smart bioinks.

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