A Decade of Organs-on-a-Chip Emulating Human Physiology at the Microscale: A Critical Status Report on Progress in Toxicology and Pharmacology

Rothbauer, Mario; Bachmann, Barbara; Eilenberger, Christoph; Kratz, Sebastian Rudi Adam; Spitz, Sarah; Höll, Gregor; Ertl, Peter

doi:10.3390/mi12050470

Cited by 33 publications

(13 citation statements)

References 244 publications

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“…In the present times single-organ-on-a-chip models have already been created for almost all organs, with some studies on multiple OoC devices interconnected ( Goldstein et al, 2021 ). One of the next development steps is the integration of sensors into the chips, which makes monitoring key physiological parameters easier ( Clarke et al, 2021 ; Rothbauer et al, 2021 ). It is an important field which with further development can lead to new and revolutionary discoveries.…”

Section: Discussionmentioning

confidence: 99%

Organ-On-A-Chip: A Survey of Technical Results and Problems

Danku

Dulf

Braicu

et al. 2022

Front. Bioeng. Biotechnol.

103

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Organ-on-a-chip (OoC), also known as micro physiological systems or “tissue chips” have attracted substantial interest in recent years due to their numerous applications, especially in precision medicine, drug development and screening. Organ-on-a-chip devices can replicate key aspects of human physiology, providing insights into the studied organ function and disease pathophysiology. Moreover, these can accurately be used in drug discovery for personalized medicine. These devices present useful substitutes to traditional preclinical cell culture methods and can reduce the use of in vivo animal studies. In the last few years OoC design technology has seen dramatic advances, leading to a wide range of biomedical applications. These advances have also revealed not only new challenges but also new opportunities. There is a need for multidisciplinary knowledge from the biomedical and engineering fields to understand and realize OoCs. The present review provides a snapshot of this fast-evolving technology, discusses current applications and highlights advantages and disadvantages for biomedical approaches.

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Section: Discussionmentioning

confidence: 99%

Organ-On-A-Chip: A Survey of Technical Results and Problems

Danku

Dulf

Braicu

et al. 2022

Front. Bioeng. Biotechnol.

103

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“…Although there has been recent progress in microfabrication and design, which has rendered microchips extremely performant in several bioapplications, some technical complications still persist. [ 438–441 ] One of the major concerns to deal with in the next future is the incompatibility of chip materials with hydrophilic matter. [ 442 ] For example, systems made of widely used PDMS pose challenges in relation to their integrability with biomaterials and cells.…”

Section: Discussionmentioning

confidence: 99%

“…still persist. [438][439][440][441] One of the major concerns to deal with in the next future is the incompatibility of chip materials with hydrophilic matter. [442] For example, systems made of widely used PDMS pose challenges in relation to their integrability with biomaterials and cells.…”

Section: Discussionmentioning

confidence: 99%

Microfluidic Tissue Engineering and Bio‐Actuation

et al. 2022

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Bio‐hybrid technologies aim to replicate the unique capabilities of biological systems that could surpass advanced artificial technologies. Soft bio‐hybrid robots consist of synthetic and living materials and have the potential to self‐assemble, regenerate, work autonomously, and interact safely with other species and the environment. Cells require a sufficient exchange of nutrients and gases, which is guaranteed by convection and diffusive transport through liquid media. The functional development and long‐term survival of biological tissues in vitro can be improved by dynamic flow culture, but only microfluidic flow control can develop tissue with fine structuring and regulation at the microscale. Full control of tissue growth at the microscale will eventually lead to functional macroscale constructs, which are needed as the biological component of soft bio‐hybrid technologies. This review summarizes recent progress in microfluidic techniques to engineer biological tissues, focusing on the use of muscle cells for robotic bio‐actuation. Moreover, the instances in which bio‐actuation technologies greatly benefit from fusion with microfluidics are highlighted, which include: the microfabrication of matrices, biomimicry of cell microenvironments, tissue maturation, perfusion, and vascularization.

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“…Consequently, the quest to test and improve the clinical relevance of this novel generation of (micro)biomedical devices for culturing tissues and modeling organ functions out-of-plane exploiting microfluidic concepts in the so-called three-dimensional (3D) models, progressed with the identification of our knowledge gap in toxicology and drug metabolism studies. 5,6 Benam et al, 7 for example, emphasized in their review on engineering in vitro disease models, the merging of tissue engineering and microfabrication as being beneficial in 2015. More recent attention to OoCs and their exploitation was given in papers by Vunjak-Novakovic et al 8 and Low et al, 9 both highlighting the onset of OoC technology readiness toward human in vitro organ models.…”

Section: Introductionmentioning

confidence: 99%

Nanofabricating neural networks: Strategies, advances, and challenges

Lüttge

2022

Journal of Vacuum Science &Amp; Technology B

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Nanofabrication can help us to emulate natural intelligence. Forward-engineering brain gained enormous momentum but still falls short in human neurodegenerative disease modeling. Here, organ-on-chip (OoC) implementation of tissue culture concepts in microfluidic formats already progressed with the identification of our knowledge gap in toxicology and drug metabolism studies. We believe that the self-organization of stem cells and chip technology is a key to advance such complex in vitro tissue models, including models of the human nervous system as envisaged in this review. However, current cultured networks of neurons show limited resemblance with the biological functions in the real nervous system or brain tissues. To take full advantage of scaling in the engineering domain of electron-, ion-, and photon beam technology and nanofabrication methods, more research is needed to meet the requirements of this specific field of chip technology applications. So far, surface topographies, microfluidics, and sensor and actuator integration concepts have all contributed to the patterning and control of neural network formation processes in vitro. However, when probing the state of the art for this type of miniaturized three-dimensional tissue models in PubMed, it was realized that there is very little systematic cross-disciplinary research with biomaterials originally formed for tissue engineering purposes translated to on-chip solutions for in vitro modeling. Therefore, this review contributes to the formulation of a sound design concept based on the understanding of the existing knowledge and the technical challenges toward finding better treatments and potential cures for devastating neurodegenerative diseases, like Parkinson's disease. Subsequently, an integration strategy based on a modular approach is proposed for nervous system-on-chip (NoC) models that can yield efficient and informative optical and electronic NoC readouts in validating and optimizing these conceptual choices in the innovative process of a fast growing and exciting new OoC industry.

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A Decade of Organs-on-a-Chip Emulating Human Physiology at the Microscale: A Critical Status Report on Progress in Toxicology and Pharmacology

Cited by 33 publications

References 244 publications

Organ-On-A-Chip: A Survey of Technical Results and Problems

Organ-On-A-Chip: A Survey of Technical Results and Problems

Microfluidic Tissue Engineering and Bio‐Actuation

Nanofabricating neural networks: Strategies, advances, and challenges

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