Bioprinted 3D Primary Human Intestinal Tissues Model Aspects of Native Physiology and ADME/Tox Functions

Madden, Lauran; Nguyen, Theresa V.; Garcia-Mojica, Salvador; Shah, Vishal; Le, Alex V.; Peier, Andrea; Visconti, Richard; Parker, Eric M.; Presnell, Sharon C.; Nguyen, Deborah G.; Retting, Kelsey N.

doi:10.1016/j.isci.2018.03.015

Cited by 127 publications

(102 citation statements)

References 38 publications

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“…Concerning the potentials of intestinal organoids in gut repair, preparations of organoid‐laden scaffolds that accord with intestinal tract anatomy are of great basic and clinical importance. To realize this purpose, development of printable and organoid‐compatible hydrogels is promising because they can be used to produce personalized scaffolds by 3D‐printing technology (Huang et al, ; Madden et al, ; Xu, Ren, Huang, Li, & Ren, ). Moreover, compared with chemical fluorescent compounds, fusion of fluorescent protein genes using CRISPR‐Cas9 causes the least influence to intestinal organoids.…”

Section: Future Directionsmentioning

confidence: 99%

Biomaterials and biosensors in intestinal organoid culture, a progress review

Huang

Jiang

Ren

et al. 2020

J Biomedical Materials Res

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As an emerging technology, intestinal organoids are promising new tools for basic and translational research in gastroenterology. Currently, culture of intestinal organoids relies mostly on a type of tumor-derived scaffolds, namely Matrigel, which may pose tumorigenic risks to organoid implantation. Apart from the traditional detection methods, such as tissue slicing and fluorescence staining, the monitoring of intestinal organoids requires real-time biosensors that can adapt to their threedimensional dynamic growth patterns. In this review, we summarized the recent advances in developing definite hydrogel scaffolds for intestinal organoid culture and identified key parameters for scaffold design. In addition, classified by different substrate compositions like pH, electrolytes, and functional proteins, we concluded the existing live-imaging biosensors and elucidated their underlying mechanisms. We hope this review enhances the understanding of intestinal organoid culture and provides more practical approaches to investigate them. K E Y W O R D Sbiosensor, intestinal stem cell, organoid, regenerative medicine, scaffold design

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Section: Future Directionsmentioning

confidence: 99%

Biomaterials and biosensors in intestinal organoid culture, a progress review

Huang

Jiang

Ren

et al. 2020

J Biomedical Materials Res

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“…Cell therapy for the skin repair has been conducted in vitro , but it is challenging to be applied to animal models in vivo because of the high risks of cell contamination and difficulties in constructing layered skin. The 3D bioprinting has provided technology to build the multilayer structure of tissues, therefore the chitosan‐based hydrogels should be designed with a shear‐thinning property, which is favored for the extrusion or injection‐based bioprinting applications …”

Section: Multiple Applicationsmentioning

confidence: 99%

Hydrogels based on chitosan in tissue regeneration: How do they work? A mini review

Jiao

Huang

Zhang

2018

J of Applied Polymer Sci

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The repair of tissue defects after injury is of significant clinical and research importance. A variety of chitosan‐based hydrogels have been investigated and applied to address this problem. By using different synthetic methods, the hydrogels exhibit distinct physical properties, including porosity, adhesion, and stiffness. These properties are considered important factors affecting cell proliferation and tissue regeneration. Meanwhile, drug delivery and cell delivery are the two main strategies to improve the therapeutic effects of chitosan‐based hydrogels, but the choices of cells or drugs are quite varied and largely depend on the specificity of the treated tissues. The present review summarizes the physicochemical properties of chitosan‐based hydrogels and their influences on cells, and lists specific ways to promote the tissue regeneration in different systems of the human body. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47235.

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“…Epithelial monolayers provide a simplified tool to study these complex interactions in a controlled manner, and coculture with fibroblasts, bacteria, viruses, protozoa, neurons, and immune cells have all been demonstrated in recent years [66][67][68][69][70][71][72][73]. Placement of fibroblast feeder layers yields a layered tissue suitable for long-term epithelial culture or drug absorption and toxicity assays (Figure 3) [66,70,74]. Coculture of epithelium with enteric neurons is in its early stages but will certainly provide novel insights into neurointestinal crosstalk [73].…”

Section: Box 3 Support Matrixmentioning

confidence: 99%

Primary Cell-Derived Intestinal Models: Recapitulating Physiology

Dutton

Hinman

Kim

et al. 2019

Trends in Biotechnology

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The development of physiologically relevant intestinal models fueled by breakthroughs in primary cell-culture methods has enabled successful recapitulation of key features of intestinal physiology. These advances, paired with engineering methods, for example incorporating chemical gradients or physical forces across the tissues, have yielded ever more sophisticated systems that enhance our understanding of the impact of the host microbiome on human physiology as well as on the genesis of intestinal diseases such as inflammatory bowel disease and colon cancer. In this review we highlight recent advances in the development and usage of primary cell-derived intestinal models incorporating monolayers, organoids, microengineered platforms, and macrostructured systems, and discuss the expected directions of the field. Current Approaches to Modeling Intestinal Physiology The small and large intestine, located after the stomach, comprise the lower human gastrointestinal tract and play crucial roles in nutrient absorption and in housing much of the human microbiome (see Glossary) (Figure 1, Key Figure). In the past decade, model systems have attempted to recapitulate the complex, in vivo intestinal physiology using cell lines derived from intestinal tumors such as Caco-2 cells in place of primary epithelial cells. Advanced organ-on-achip systems were created by culturing Caco-2 cells on the geometrically or mechanically engineered platforms to properly mimic the structural and mechanical properties of the human intestine [1-6]. To mimic the mucosal architecture, porous scaffolds were micromolded to villus-like projections on which Caco-2 cells could be cultured [1,6]. To recapitulate the mechanically dynamic environment, microfluidic systems were developed with fluid flowing both above and below a Caco-2 cell layer growing on a rhythmically stretched flexible surface [2-5]. These systems were designed to mimic the shear forces and contractile motions occurring in the small intestine. Caco-2 cells, as well as other tumor cell lines, have also been used as surrogate intestinal epithelial cells to probe the interactions between multiple tissue types [7]. These organ-on-a-chip models incorporating tumor cells offer new abilities to emulate the structure, function, and physiology of the living human intestine that are not possible with conventional tissue-cultured monolayers. However, as our understanding of these organs progresses, it is clear that these prior tumor model systems fall short in their ability to accurately reflect in vivo physiology because the models do not possess all of the intestinal epithelial subtypes and either lack receptors, transporters, drug-metabolizing enzymes, or express these proteins at levels different from in vivo. Thus, in vitro replicas of the intestines that more accurately replicate intestinal physiology are required and will need to utilize primary cells. Accordingly, a suite of platforms employing primary cells in a variety of assay formats, including organoid [8,9], monolayer, and shape...

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Bioprinted 3D Primary Human Intestinal Tissues Model Aspects of Native Physiology and ADME/Tox Functions

Cited by 127 publications

References 38 publications

Biomaterials and biosensors in intestinal organoid culture, a progress review

Biomaterials and biosensors in intestinal organoid culture, a progress review

Hydrogels based on chitosan in tissue regeneration: How do they work? A mini review

Primary Cell-Derived Intestinal Models: Recapitulating Physiology

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