Bioinspired Three-Dimensional Human Neuromuscular Junction Development in Suspended Hydrogel Arrays

Dixon, T. A.; Cohen, Eliad; Cairns, Dana M.; Rodrí­guez, Marí­a José; Mathews, Juanita; Jose, Rod R.; Kaplan, David L.

doi:10.1089/ten.tec.2018.0062

Cited by 41 publications

(34 citation statements)

References 64 publications

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“…In one study, silk fibroin was used as scaffolds to support the growth and differentiation of hiPSC‐derived kidney organoids . Silk has been widely used to support growth of cornea, gastrointestinal tissues, and neural tissue due to its properties of biocompatibility, safety and adjustable degradability and its ability to be modified by incorporation of macromolecules. Recently, avidin was incorporated into the silk material, thus biotinylated proteins (e.g., growth factors) can be conjugated to increase their local concentration, which could possibly provide instructive signals to guide tissue morphogenesis in the scaffold .…”

Section: Hydrogels In Organoids Formationmentioning

confidence: 99%

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: Hydrogels In Organoids Formationmentioning

confidence: 99%

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

et al. 2019

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“…In addition to native and brain-derived components, ECM proteins of nonmammalian origin such as silk fibroin (SF) have been used as successful bioink component to print neural cell lines. [104] Finally, despite such availability of different natural materials to establish fully chemically defined bioinks, complex mixtures of ECM components, such as Matrigel, still remain a preferred culture substrate for neurons. 3D cultures in Matrigel were shown to support long-term survival of neural cells up to 5 months [105] as well as to permit the culture of multicellular structures like midbrain-mimetic organoids.…”

Section: Natural-origin Hydrogelsmentioning

confidence: 99%

Bioprinting Neural Systems to Model Central Nervous System Diseases

Qiu

Bessler

Figler

et al. 2020

Adv Funct Materials

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To date, pharmaceutical progresses in central nervous system (CNS) diseases are clearly hampered by the lack of suitable disease models. Indeed, animal models do not faithfully represent human neurodegenerative processes and human in vitro 2D cell culture systems cannot recapitulate the in vivo complexity of neural systems. The search for valuable models of neurodegenerative diseases has recently been revived by the addition of 3D culture that allows to recreate the in vivo microenvironment including the interactions among different neural cell types and the surrounding extracellular matrix (ECM) components. In this review, the new challenges in the field of CNS diseases in vitro 3D modeling are discussed, focusing on the implementation of bioprinting approaches enabling positional control on the generation of the 3D microenvironments. The focus is specifically on the choice of the optimal materials to simulate the ECM brain compartment and the biofabrication technologies needed to shape the cellular components within a microenvironment that significantly represents brain biochemical and biophysical parameters.

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“…This strategy has been applied to develop a threedimensional (3D) human muscle model with endothelium specificity and endomysium for the study of fibrosis 22 . Importantly, the motor neurons have been cultured with the bioengineered muscle to better understand the development and maturation of neuromuscular junctions (NMJs) 23,24 .…”

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confidence: 99%

Neural cell integration into 3D bioprinted skeletal muscle constructs accelerates restoration of muscle function

et al. 2020

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A bioengineered skeletal muscle construct that mimics structural and functional characteristics of native skeletal muscle is a promising therapeutic option to treat extensive muscle defect injuries. We previously showed that bioprinted human skeletal muscle constructs were able to form multi-layered bundles with aligned myofibers. In this study, we investigate the effects of neural cell integration into the bioprinted skeletal muscle construct to accelerate functional muscle regeneration in vivo. Neural input into this bioprinted skeletal muscle construct shows the improvement of myofiber formation, long-term survival, and neuromuscular junction formation in vitro. More importantly, the bioprinted constructs with neural cell integration facilitate rapid innervation and mature into organized muscle tissue that restores normal muscle weight and function in a rodent model of muscle defect injury. These results suggest that the 3D bioprinted human neural-skeletal muscle constructs can be rapidly integrated with the host neural network, resulting in accelerated muscle function restoration.

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Bioinspired Three-Dimensional Human Neuromuscular Junction Development in Suspended Hydrogel Arrays

Cited by 41 publications

References 64 publications

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

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

Bioprinting Neural Systems to Model Central Nervous System Diseases

Neural cell integration into 3D bioprinted skeletal muscle constructs accelerates restoration of muscle function

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