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A Linkable, Polycarbonate Gut Microbiome-Distal Tumor Chip Platform for Interrogating Cancer Promoting Mechanisms
Danielle S K Brasino1, Sean D Speese1, Kevin Schilling1
1Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA.
Abstract:
Gut microbiome composition is tied to diseases ranging from arthritis to cancer to depression. However, mechanisms of action are poorly understood, limiting development of relevant therapeutics. Organ-on-chip platforms, which model minimal functional units of tissues and can tightly control communication between them, are ideal platforms to study these relationships. Many gut microbiome models are published to date but devices are typically fabricated using oxygen permeable polydimethylsiloxane, requiring interventions to support anaerobic bacteria. To address this challenge, a platform is developed where the chips are fabricated entirely from gas-impermeable polycarbonate without tapes or gaskets. These chips replicate polarized villus-like structures of the native tissue. Further, they enable co-cultures of commensal anaerobic bacteria Blautia coccoides on the surface of gut epithelia for two days within a standard incubator. Another complication of commonly used materials in organ-on-chip devices is high ad-/absorption, limiting applications in high-resolution microscopy and biomolecule interaction studies. For future communication studies between gut microbiota and distal tumors, an additional polycarbonate chip design is developed to support hydrogel-embedded tissue culture. These chips enable high-resolution microscopy with all relevant processing done on-chip. Designed for facile linking, this platform will make a variety of mechanistic studies possible.
Insights
A novel organ-on-chip platform made from polycarbonate enables the study of gut microbiome interactions with human gut tissues. This technology overcomes limitations of previous models, facilitating research into gut bacteria and disease mechanisms.
Area of Science:
- Biomedical Engineering
- Microbiology
- Gastroenterology
Background:
- Gut microbiome composition is linked to various diseases, but underlying mechanisms remain unclear, hindering therapeutic development.
- Organ-on-chip technology offers a controlled environment to study tissue and microbial interactions.
- Existing gut-on-chip models often use oxygen-permeable materials, complicating the study of anaerobic gut bacteria.
Purpose of the Study:
- To develop an improved organ-on-chip platform for studying gut microbiome-host interactions.
- To overcome material limitations in current organ-on-chip devices for anaerobic bacterial co-culture.
- To enable high-resolution imaging and biomolecule studies of gut microbiota-epithelia communication.
Main Methods:
- Fabrication of organ-on-chip devices entirely from gas-impermeable polycarbonate.
- Replication of polarized villus-like structures within the polycarbonate chips.
- Co-culture of anaerobic bacteria (Blautia coccoides) with gut epithelia on-chip.
- Development of a secondary chip design for hydrogel-embedded tissue culture and on-chip processing.
Main Results:
- The polycarbonate chips successfully supported co-culture of anaerobic bacteria with gut epithelia for two days in a standard incubator.
- The gas-impermeable nature of the chips eliminated the need for interventions to maintain anaerobic conditions.
- The platform demonstrated suitability for high-resolution microscopy and on-chip processing, addressing material absorption issues.
Conclusions:
- The developed polycarbonate organ-on-chip platform provides a robust system for studying anaerobic gut bacteria and host interactions.
- This technology facilitates mechanistic studies of the gut microbiome's role in health and disease.
- The platform's design enables future investigations into microbiota-host communication, including interactions with distal tissues like tumors.
