Microphysiological systems: What it takes for community adoption

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

doi:10.1177/15353702211008872

Cited by 15 publications

(12 citation statements)

References 143 publications

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“…Keys to translational implementation MPS models of musculoskeletal pathologies include developing strategies to: engineer vascular and biological barriers and heterogenous tissue interfaces; incorporate immune cells and inflammatory factors; enable biomechanical actuation to simulate in vivo loading; incorporate sensory neurons (nociceptors) to record surrogate measurements for pain; integrate inline sensors for real-time monitoring of secreted proteins critical to modulating these dynamic processes; and develop arrayed formats for high throughput screening. Furthermore, issues of scalability, reproducibility, and validation, which are not discussed in this review, are also of paramount importance and have been addressed in other reviews ( Hargrove-Grimes et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery

Ajalik

Alenchery

Cognetti

et al. 2022

Front. Bioeng. Biotechnol.

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Human Microphysiological Systems (hMPS), otherwise known as organ- and tissue-on-a-chip models, are an emerging technology with the potential to replace in vivo animal studies with in vitro models that emulate human physiology at basic levels. hMPS platforms are designed to overcome limitations of two-dimensional (2D) cell culture systems by mimicking 3D tissue organization and microenvironmental cues that are physiologically and clinically relevant. Unlike animal studies, hMPS models can be configured for high content or high throughput screening in preclinical drug development. Applications in modeling acute and chronic injuries in the musculoskeletal system are slowly developing. However, the complexity and load bearing nature of musculoskeletal tissues and joints present unique challenges related to our limited understanding of disease mechanisms and the lack of consensus biomarkers to guide biological therapy development. With emphasis on examples of modeling musculoskeletal tissues, joints on chips, and organoids, this review highlights current trends of microphysiological systems technology. The review surveys state-of-the-art design and fabrication considerations inspired by lessons from bioreactors and biological variables emphasizing the role of induced pluripotent stem cells and genetic engineering in creating isogenic, patient-specific multicellular hMPS. The major challenges in modeling musculoskeletal tissues using hMPS chips are identified, including incorporating biological barriers, simulating joint compartments and heterogenous tissue interfaces, simulating immune interactions and inflammatory factors, simulating effects of in vivo loading, recording nociceptors responses as surrogates for pain outcomes, modeling the dynamic injury and healing responses by monitoring secreted proteins in real time, and creating arrayed formats for robotic high throughput screens. Overcoming these barriers will revolutionize musculoskeletal research by enabling physiologically relevant, predictive models of human tissues and joint diseases to accelerate and de-risk therapeutic discovery and translation to the clinic.

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Section: Discussionmentioning

confidence: 99%

Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery

Ajalik

Alenchery

Cognetti

et al. 2022

Front. Bioeng. Biotechnol.

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“…For example, the human-on-a-chip (HoaC) or organ-on-a-chip 58,67 is a novel CNNbased model that mimics human organ functionality in interconnected in-vitro bioengineered micro-physiological systems. This medical imaging technology can recapitulate clinical trials on a chip (CToCs) 68 lowering the costs and recruitment barriers related to conducting RD clinical trials (scarce number of RD patients) 57 There must be clear and continuous outreach efforts to educate patients regarding AI advancements in RD diagnosis and treatments. 71 Grass-root organizations should educate the RD community and patients on the challenges and opportunities of AI-based RD diagnostic tools while building trust and helping to identify inappropriate adoption of AI in health care.…”

Section: Ai-based Genetic Devicesmentioning

confidence: 99%

Artificial Intelligence in Medical Imaging and its Impact on the Rare Disease Community: Threats, Challenges and Opportunities

et al. 2022

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“…In Consortium for Innovation and Quality in Pharmaceutical Development (also known as the IQ Consortium) has helped define MPS context of use within the industrial sector with the development of the IQ MPS Affiliate, which allows for cross-pharma collaboration, data sharing, implementation, and qualification of MPSs. The IQ MPS Affiliate has also pointed out the need for standards, comparing pre-clinical animal study results with MPS data, producing enough data for reliability and confidence in the technology, and increased throughput for MPSs to continue to grow and be adopted [67].…”

Section: Synergistic Partnerships Between Industry and Regulatory Bodies Are Driving Broad Adoption Of Oocs And Mpssmentioning

confidence: 99%

Modelling Human Physiology on-Chip: Historical Perspectives and Future Directions

2021

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For centuries, animal experiments have contributed much to our understanding of mechanisms of human disease, but their value in predicting the effectiveness of drug treatments in the clinic has remained controversial. Animal models, including genetically modified ones and experimentally induced pathologies, often do not accurately reflect disease in humans, and therefore do not predict with sufficient certainty what will happen in humans. Organ-on-chip (OOC) technology and bioengineered tissues have emerged as promising alternatives to traditional animal testing for a wide range of applications in biological defence, drug discovery and development, and precision medicine, offering a potential alternative. Recent technological breakthroughs in stem cell and organoid biology, OOC technology, and 3D bioprinting have all contributed to a tremendous progress in our ability to design, assemble and manufacture living organ biomimetic systems that more accurately reflect the structural and functional characteristics of human tissue in vitro, and enable improved predictions of human responses to drugs and environmental stimuli. Here, we provide a historical perspective on the evolution of the field of bioengineering, focusing on the most salient milestones that enabled control of internal and external cell microenvironment. We introduce the concepts of OOCs and Microphysiological systems (MPSs), review various chip designs and microfabrication methods used to construct OOCs, focusing on blood-brain barrier as an example, and discuss existing challenges and limitations. Finally, we provide an overview on emerging strategies for 3D bioprinting of MPSs and comment on the potential role of these devices in precision medicine.

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Microphysiological systems: What it takes for community adoption

Cited by 15 publications

References 143 publications

Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery

Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery

Artificial Intelligence in Medical Imaging and its Impact on the Rare Disease Community: Threats, Challenges and Opportunities

Modelling Human Physiology on-Chip: Historical Perspectives and Future Directions

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