Microphysiological Systems: Stakeholder Challenges to Adoption in Drug Development

Hargrove-Grimes, Passley; Low, Lucie A.; Tagle, Danilo A.

doi:10.1159/000517422

Cited by 26 publications

(19 citation statements)

References 108 publications

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“…The question of what will be required to enable eventual acceptance of human organ chips in lieu of preclinical animal models, their integration into drug development pipelines, and inclusion of data generated using these models in FDA regulatory submissions is a complex one 114 , 115 . One point that is clear is that this process will probably occur gradually and involve replacement of one particular animal model at a time.…”

Section: What Will It Take To Replace Animal Models?mentioning

confidence: 99%

Human organs-on-chips for disease modelling, drug development and personalized medicine

2022

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The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology with high fidelity. Here, I review how single and multiple human organ chip systems have been used to model complex diseases and rare genetic disorders, to study host–microbiome interactions, to recapitulate whole-body inter-organ physiology and to reproduce human clinical responses to drugs, radiation, toxins and infectious pathogens. I also address the challenges that must be overcome for organ chips to be accepted by the pharmaceutical industry and regulatory agencies, as well as discuss recent advances in the field. It is evident that the use of human organ chips instead of animal models for drug development and as living avatars for personalized medicine is ever closer to realization.

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Section: What Will It Take To Replace Animal Models?mentioning

confidence: 99%

Human organs-on-chips for disease modelling, drug development and personalized medicine

2022

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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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“…The breakthrough technology of microphysiological systems (MPS) has been changing preclinical research by allowing the successful development of biologically relevant human models [ 131 ]. The possibility of cultivating human cells in a very controlled microenvironment, mimicking physiological functions of tissue and organs, permits the performance of more physiologically relevant, predictive, and ethical methods to be used during drug discovery and development [ 132 ]. MPS, also frequently known as organ-on-a-chip, are usually defined as miniaturized cell culture platforms containing human or animal cells and tissues in a way to reproduce the physiological functions of one or more organs.…”

Section: Alternative Methods To Animal Testing In Adipogenesismentioning

confidence: 99%

Alternative Methods as Tools for Obesity Research: In Vitro and In Silico Approaches

Pamplona

Zoehler²,

Shigunov³

et al. 2022

Life

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The study of adipogenesis is essential for understanding and treating obesity, a multifactorial problem related to body fat accumulation that leads to several life-threatening diseases, becoming one of the most critical public health problems worldwide. In this review, we propose to provide the highlights of the adipogenesis study based on in vitro differentiation of human mesenchymal stem cells (hMSCs). We list in silico methods, such as molecular docking for identification of molecular targets, and in vitro approaches, from 2D, more straightforward and applied for screening large libraries of substances, to more representative physiological models, such as 3D and bioprinting models. We also describe the development of physiological models based on microfluidic systems applied to investigate adipogenesis in vitro. We intend to identify the main alternative models for adipogenesis evaluation, contributing to the direction of preclinical research in obesity. Future directions indicate the association of in silico and in vitro techniques to bring a clear picture of alternative methods based on adipogenesis as a tool for obesity research.

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Microphysiological Systems: Stakeholder Challenges to Adoption in Drug Development

Cited by 26 publications

References 108 publications

Human organs-on-chips for disease modelling, drug development and personalized medicine

Human organs-on-chips for disease modelling, drug development and personalized medicine

Microfluidic Tissue Engineering and Bio‐Actuation

Alternative Methods as Tools for Obesity Research: In Vitro and In Silico Approaches

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