Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models

Liaw, Chya Yan; Ji, Shen; Guvendiren, Murat

doi:10.1002/adhm.201701165

Cited by 111 publications

(96 citation statements)

References 221 publications

(178 reference statements)

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“…Natural hydrogels including polysaccharides, proteins, and animal‐derived mixtures are frequently used for cell culture due to their biodegradability, physiochemical properties, and capability of gelling in mild conditions . They are either ECM‐derived components or ECM analogues, of which the chemical composites and fibrous structure are similar to that of native ECM.…”

Section: Snapshot Of Hydrogelsmentioning

confidence: 99%

“…Polysaccharides with fast gelation properties are appropriate for the fabrication of complex 3D scaffolds with various morphologies, such as microfibers, microspheres, membranes, and defined blocks, thus providing architectural cues for tissue/organ constructs in vitro. The natural proteins used as cell culture matrices are collagen, gelatin, fibrin, silk protein (mainly referring to silk fibroin), poly‐ l ‐lysine (PLL), and soy protein . These proteins can interact with cells and supply physiologically relevant microenvironments to guide cellular behaviors by presenting componential cues .…”

Section: Snapshot Of Hydrogelsmentioning

confidence: 99%

“…The natural proteins used as cell culture matrices are collagen, gelatin, fibrin, silk protein (mainly referring to silk fibroin), poly‐ l ‐lysine (PLL), and soy protein . These proteins can interact with cells and supply physiologically relevant microenvironments to guide cellular behaviors by presenting componential cues . In addition, Matrigel and decellularized extracellular matrices (dECM) are typical animal‐derived mixtures of various polysaccharides (e.g., HA and heparan), proteins (e.g., collagen and laminin), and growth factors.…”

Section: Snapshot Of Hydrogelsmentioning

confidence: 99%

“…These proteins can interact with cells and supply physiologically relevant microenvironments to guide cellular behaviors by presenting componential cues . In addition, Matrigel and decellularized extracellular matrices (dECM) are typical animal‐derived mixtures of various polysaccharides (e.g., HA and heparan), proteins (e.g., collagen and laminin), and growth factors. Usually, they render the biocompatibility and bioactivity of specific tissues that matter in cell survival and growth.…”

Section: Snapshot Of Hydrogelsmentioning

confidence: 99%

“…Hydrogels with high water content can mimic the native ECM microenvironment by spatiotemporal control over biochemical and physical cues due to their high biocompatibility and tunable properties, such as permeability, elasticity, stiffness and chemical reactivity. Various natural and synthetic hydrogels have been utilized to generate tissues by guiding a series of cellular behaviors (e.g., cell adhesion, proliferation, differentiation) in 3D cell culture. Particularly, chemically defined hydrogels can serve as biomimetic matrix or scaffold for instructing 3D tissues formation in organoids and OOC systems.…”

Section: Introductionmentioning

confidence: 99%

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Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Section: Snapshot Of Hydrogelsmentioning

confidence: 99%

Section: Snapshot Of Hydrogelsmentioning

confidence: 99%

Section: Snapshot Of Hydrogelsmentioning

confidence: 99%

Section: Snapshot Of Hydrogelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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Microfluidics‐Assisted Fabrication of Microtissues with Tunable Physical Properties for Developing an In Vitro Multiplex Tissue Model

Lee

Cha

2018

Adv. Biosys.

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Herein, a new 3D hydrogel‐based co‐culture tissue model is developed to systematically examine the effect of mutual influence between two different cell types residing in separated but interactive zones. Microtissues containing macrophage as a model cell type are first developed by photo‐crosslinking cell‐laden droplets containing methacrylic gelatin (MGel), using a microfluidic flow‐focusing device. Regardless of the material conditions, the cell viability is well maintained, demonstrating the biocompatibility of the fabrication process as well as the 3D microenvironment provided by the microgels. More significantly, it is shown that the proliferation and lipopolysaccharide (LPS)‐induced differentiation (Mφ polarization) of macrophages are heavily influenced by the mechanical properties of the microgels, controlled with MGel concentrations. Eventually, these macrophage microtissues are embedded into a larger tissue construct, containing either normal or cancer cells, to develop a co‐culture tissue model to study the mutual effects between macrophages in different stages of differentiation and the surrounding cells. It is expected that this “multiplex” tissue model would allow an effective platform for monitoring of complex interactions between two different cell types residing in adjacent, compartmentalized areas within a 3D tissue environment.

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The Construction and Application of Three‐Dimensional Biomaterials

Wang

Guo

et al. 2020

Adv. Biosys.

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Biomaterials have been widely explored and applied in many areas, especially in the field of tissue engineering. The interface of biomaterials and cells has been deeply investigated. However, it has been demonstrated that conventional 2D biomaterials fail to maintain the 3D structures and phenotypes of cells, which is the result of their limited ability to mimic the latter's complex extracellular matrix. To overcome this challenge, cell cultivation dependent on 3D biomaterials has emerged as an alternative strategy to make the recovery of 3D structures and functions of cells possible. Thus, with the thriving development of 3D cell culture in tissue engineering, a holistic review of the construction and application of 3D biomaterials is desired. Here, recent developments in 3D biomaterials for tissue engineering are reviewed. An overview of various approaches to construct 3D biomaterials, such as electro‐jetting/‐spinning, micro‐molding, microfluidics, and 3D bio‐printing, is first presented. Their typical applications in constructing cell sheets, vascular structures, cell spheroids, and macroscopic cellular constructs are described as well. Following these two sections, the current status and challenges are analyzed, as well as the future outlook of 3D biomaterials for tissue engineering.

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Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models

Cited by 111 publications

References 221 publications

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Microfluidics‐Assisted Fabrication of Microtissues with Tunable Physical Properties for Developing an In Vitro Multiplex Tissue Model

The Construction and Application of Three‐Dimensional Biomaterials

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