Bio-HhOST

Cell interaction in next generation 3D tissue models

Writer

Celeste Chidiac, PhD

Keywords

Microfluidic Devices, Intelligent Microfluidics, Artificial Intelligence, Machine Learning

Author

Marlene Kopf

Publication Date

June 24, 2024

Keywords

Intelligent Microfluidics

Deep Learning

Microfluidic Devices

Artificial Intelligence

Machine Learning

3D tissue models

Cell interaction

Cell perfusion

Your microfluidic SME partner for Horizon Europe

We take care of microfluidic engineering, work on valorization and optimize the proposal with you 

An interdisciplinary consortium to observe cell interaction

The Bio-HhOST project aims to develop bio-hybrid materials integrating living and artificial cells to observe cell interaction, allowing artificial cells to influence the growth, differentiation, and function of living cells. We are working on Bio-HhOST with interdisciplinary team of biologists, engineers, mathematicians, and entrepreneurs.

In the project Bio-HhOST, we aim to create precision-engineered artificial cells made of liquid and lipid bilayers, compartmentalized chemically, and co-located with live cells to induce cell interaction. These artificial cells will have functional metabolisms and respond to environmental chemical stimuli by releasing signaling molecules to regulate neighboring living cells, mimicking complex biological tissues and their cell interaction.

cell interaction

Project goal: understanding cell behavior in realistic 3D tissue models

The overarching goals of the project include the creation of next generation 3D tissues. In these tissues, living cell differentiation is spatially regulated by chemically programmable artificial cells. The 3D tissues are intended to be maintained through cell interaction and dynamic communication between live and artificial cells. In addition, the project partners will develop multi-level models of organoid-synthetic tissue behavior and cell interaction for targeted applications. Another important part of the project deals with the evaluation of drug delivery vectors for next-generation biological therapeutics. Moreover, complex tissues with distinct regions that are not achievable with current organoid protocols will be generated in the scope of the project.

The broader ambitions of Bio-HhOST include understanding cell behavior in realistic 3D tissue models to observe cell interaction, identifying disease treatment targets, and reducing the use of animals in pharmaceutical research. With this innovative approach, the project aims to enhance the understanding and control of physio-chemical cell interaction in tissues, offering significant advancements in biomedical science and therapeutics.

How to use microfluidics for next generation 3D tissue models: our role

cell interaction microfluidic innovation center MIC partnership project collaborationThe Microfluidics Innovation Center is working on a microfluidic flow control platform for automated cell perfusion for the Bio-Hhost project. The platform enables researchers to regulate cell growth parameters and observe cell interaction without the need for an incubator. The system will allow continuous manipulation under sterile conditions and ongoing monitoring via microscopy without disconnecting the cell culture chip from the perfusion setup.

We have also been involved in other projects related to artificial cells and cell interaction. Find out more about the projects ACDC and Protomet on our website. More information on ACDC can be found on the project’s website.

You need a microfluidics partner for your project on artificial cells as well? Drop us a line! We are interested in joining your consortium and are open to a wide variety of topics and calls, such as the Pathfinder Challenge on Solar-to-X devices dealing with biohybrid systems.

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Funding and Support

This project has received funding from the European Union’s Horizon research and innovation program under HORIZON-EIC-2023-PATHFINDEROPEN-01, grant agreement no. 101130747 (Bio-HhOST).

Start date: 1 February 2024

End date: 31 January 2027

Overall budget: € 1,226,718.83

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FAQ – Cell interaction in next generation 3D tissue models - Bio-HhOST

What problem are you trying to solve with “next-generation” 3D tissue models?

Standard 2D cultures, and many early 3D setups, don’t allow cells to communicate as they do in real tissue. Signals get flattened: mechanics, nutrient and morphogen gradients, stromal-immune crosstalk. Our goal is to rebuild that spatial organization. We control shear, diffusion, and matrix mechanics so that cell-cell and cell-matrix interactions behave more like they do in vivo.

With microfluidics, we precisely control shear, deliver factors as gradients (not one-off dumps), and create adjacent “neighborhoods” (epithelium, stroma, vasculature) that exchange signals naturally. You see steadier phenotypes, clearer polarization, and interaction patterns that last beyond one week.

Two things.

  1. Hybrid microfabrication: soft lithography plus laser micromachining and 3D micro-printing to build multi-scale features.
  2. Matrix engineering: beyond single-component gels, tunable stiffness, defined porosity, and ECM patterning so cells get mechanical, topographical, and biochemical cues at once.

We pair imaging with function. Examples: live imaging of immune synapses and cytokine flux; barrier TEER with tracer permeability under flow; single-cell omics to detect interaction-driven transcriptional programs. When we can, we benchmark against ex vivo tissue slices or primary clinical samples.

Yes. The format works with robotic liquid handling, environmental control, and multiplexed readouts (imaging, ELISA-style secretome assays, qPCR/NGS). Automation is MIC’s core activity, so we build for reliability: plate-style footprints where it helps, standardized connectors, and solid standard operating procedures (SOPs) for seeding, perfusion, and endpoints.

The architecture supports layered co-cultures, parenchyma, stroma, endothelium, and immune compartments, with independent perfusion loops if needed. Active transport of nutrients and waste products keeps cultures healthy longer, which is key to preventing immune exhaustion, stromal remodeling, or therapy resistance.

Three common use cases:

  1. Mechanism of action when cell dialogue drives response.
  2. Head-to-head evaluations of biologics or cell therapies in controlled micro-environments.
  3. De-risking translation by matching gradients, stiffness, and architecture to the target tissue.
    Teams usually start with a focused assay, then scale to semi-throughput once the biology is stable.

Typically, two roles:

  • Platform owner: design, build, and maintain the microfluidic/automation backbone.
  • Methods integrator: bridge biology, analytics, and manufacturing.
    Consortia with an experienced SME move faster on deliverables and tech transfer. We’ve supported multiple EU projects end-to-end, drafting technical work packages, harmonizing SOPs, and turning prototypes into reproducible tools. In our experience, adding MIC roughly doubles proposal success rates compared to the baseline because reviewers see a credible path from concept to a validated instrument.

A clear biological question (which interaction, and what success looks like), access to primary cells or well-characterized lines, and required readouts (live imaging, secretome, omics). We handle micro-engineering, automation, and validation; you bring the biology and clinical context. For proposals, we also help set milestones, risks, and an exploitation plan so the path to impact is obvious.

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