A practical guide to microfabrication and patterning of hydrogels for biomimetic cell culture scaffolds

Tenje, Maria; Cantoni, Federico; Hernández, Ana María Porras; Searle, Sean; Johansson, Sofia; Barbe, Laurent; Antfolk, Maria; Pohlit, Hannah

doi:10.1016/j.ooc.2020.100003

Cited by 58 publications

(67 citation statements)

References 176 publications

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“…Microfabrication of unique structures with variable stiffnesses has utility in the fabrication of biomimetic cell culture scaffolds, specifically for co‐culture models and controlling stem cell fate via material stiffness. [ 76,77 ] Typically, scaffold patterning with variable stiffness requires multiple precursor materials and fabrication steps, limiting resolution and feasibility. Pairing traditional GelMA photo‐crosslinking with coordinated gelation and crosslinking provides a new tool for spatially patterning hydrogel scaffolds for tissue engineering applications in 2D and 3D.…”

Section: Resultsmentioning

confidence: 99%

Rheological Properties of Coordinated Physical Gelation and Chemical Crosslinking in Gelatin Methacryloyl (GelMA) Hydrogels

Young

White

Daniele

2020

Macromolecular Bioscience

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Synthetically modified proteins, such as gelatin methacryloyl (GelMA), are growing in popularity for bioprinting and biofabrication. GelMA is a photocurable macromer that can rapidly form hydrogels, while also presenting bioactive peptide sequences for cellular adhesion and proliferation. The mechanical properties of GelMA are highly tunable by modifying the degree of substitution via synthesis conditions, though the effects of source material and thermal gelation have not been comprehensively characterized for lower concentration gels. Herein, the effects of animal source and processing sequence are investigated on scaffold mechanical properties. Hydrogels of 4–6 wt% are characterized. Depending on the temperature at crosslinking, the storage moduli for GelMA derived from pigs, cows, and cold‐water fish range from 723 to 7340 Pa, 516 to 3484 Pa, and 294 to 464 Pa, respectively. The maximum storage moduli are achieved only by coordinated physical gelation and chemical crosslinking. In this method, the classic thermo‐reversible gelation of gelatin occurs when GelMA is cooled below a thermal transition temperature, which is subsequently “locked in” by chemical crosslinking via photocuring. The effects of coordinated physical gelation and chemical crosslinking are demonstrated by precise photopatterning of cell‐laden microstructures, inducing different cellular behavior depending on the selected mechanical properties of GelMA.

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Section: Resultsmentioning

confidence: 99%

Rheological Properties of Coordinated Physical Gelation and Chemical Crosslinking in Gelatin Methacryloyl (GelMA) Hydrogels

Young

White

Daniele

2020

Macromolecular Bioscience

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“…[50] Entrapped cells in a confined environment, such as within hydrogel beads produced using microfluidic technology, can be analyzed on or off-chip. [51] Cell encapsulation within a microfluidic device can be achieved, usually, by combining droplet forming geometries and liquid polymers (as the dispersed phase), which, under crosslinking, form a biological scaffold for the cells to grow into 3D spheroids. [45,52] Relatively simple T-junction microfluidic geometries have been used to enable cell encapsulation and cell growth assessment in the presence of hydrogel used as the ECM.…”

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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“…The incorporation of chemical, mechanical or structural patterning allows better mimicry of the in vivo microenvironment, thus giving improved control over cell fate compared to an isotropic and homogeneous hydrogel. [231] While 3D hydrogels such as Matrigel are useful as models of the ECM in many tissue types, they are not universally applicable. For instance, the basal lamina in barrier tissues is effectively a 2D ECM and can therefore be modeled by a 2D biomaterial membrane rather than a 3D hydrogel matrix [232] for instance, collagen has been used to model the basal lamina of the placenta [233] or colon.…”

Section: Biomaterials As Ecm Mimicsmentioning

confidence: 99%

Chips for Biomaterials and Biomaterials for Chips: Recent Advances at the Interface between Microfabrication and Biomaterials Research

Guttenplan

Birgani

Giselbrecht

et al. 2021

Adv Healthcare Materials

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In recent years, the use of microfabrication techniques has allowed biomaterials studies which were originally carried out at larger length scales to be miniaturized as so-called "on-chip" experiments. These miniaturized experiments have a range of advantages which have led to an increase in their popularity. A range of biomaterial shapes and compositions are synthesized or manufactured on chip. Moreover, chips are developed to investigate specific aspects of interactions between biomaterials and biological systems. Finally, biomaterials are used in microfabricated devices to replicate the physiological microenvironment in studies using so-called "organ-on-chip," "tissue-on-chip" or "disease-on-chip" models, which can reduce the use of animal models with their inherent high cost and ethical issues, and due to the possible use of human cells can increase the translation of research from lab to clinic. This review gives an overview of recent developments at the interface between microfabrication and biomaterials science, and indicates potential future directions that the field may take. In particular, a trend toward increased scale and automation is apparent, allowing both industrial production of micron-scale biomaterials and high-throughput screening of the interaction of diverse materials libraries with cells and bioengineered tissues and organs.

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A practical guide to microfabrication and patterning of hydrogels for biomimetic cell culture scaffolds

Cited by 58 publications

References 176 publications

Rheological Properties of Coordinated Physical Gelation and Chemical Crosslinking in Gelatin Methacryloyl (GelMA) Hydrogels

Rheological Properties of Coordinated Physical Gelation and Chemical Crosslinking in Gelatin Methacryloyl (GelMA) Hydrogels

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

Chips for Biomaterials and Biomaterials for Chips: Recent Advances at the Interface between Microfabrication and Biomaterials Research

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