Periodic Reporting for period 1 - TissMec (3D screening system to cultivate tissue and automatically stimulate and quantify its mechanical properties)
Período documentado: 2024-03-01 hasta 2025-08-31
Developing a new drug is extraordinarily costly and slow, with average investments of around two billion euros per approved compound. One key reason is that promising drug candidates often fail late in the process—during animal experiments or clinical trials—because existing testing approaches cannot faithfully predict how a compound will affect real human tissues. Conventional two-dimensional cell cultures lack physiological relevance, and while modern three-dimensional (3D) tissue models offer a major improvement, the field still lacks fast, automated, and quantitative ways to evaluate whether a drug alters the functional properties of these tissues. This gap is especially critical for organs such as heart, skeletal muscle, skin, and brain, whose healthy function fundamentally depends on their mechanical integrity.
Our project addresses this unmet need by developing TissMec, a new technology that enables fully automated cultivation, stimulation, and mechanical characterization of human 3D tissues. TissMec builds on an earlier generation of tissue-growth chambers developed under the ERC Consolidator Grant PolarizeMe, which already enable scalable growth and imaging of human muscle tissue. However, current systems cannot measure essential physical tissue functions—such as force generation, stiffness, or viscosity—and they require manual imaging steps that make high-throughput screening impractical.
TissMec introduces a breakthrough solution: a compact, scalable chamber that combines optical fiber–based force detection, piezoelectric actuation, and direct optical access for high-resolution microscopy. This integrated platform allows drug candidates to be tested on human-derived tissues while automatically quantifying how they affect tissue mechanics—an essential marker for safety and efficacy that is currently inaccessible in high-throughput formats. In contrast to existing commercial systems, TissMec can stimulate tissues electrically, apply defined mechanical loads, mimic pathological mechanical environments (such as heart failure or fibrosis), and read out tissue mechanics without requiring a microscope. The system is designed to be compatible with standard multi-well formats, enabling direct integration into widely used industrial screening pipelines.
The expected impact is substantial. By providing early, reliable, and fully automated tests on human tissue, TissMec has the potential to dramatically reduce the number of ineffective or harmful compounds entering animal experiments or clinical trials—thereby lowering development costs, reducing animal use, and accelerating innovation in drug discovery. The technology is relevant not only for pharmaceutical companies but also for academic researchers and chemical safety testing, particularly as European and US policy increasingly encourages alternatives to animal-based testing.
In summary, TissMec introduces a transformative approach to functional 3D tissue screening. By merging tissue engineering, precision mechanics, and automated optical measurement in a single scalable platform, the project aims to make high-content mechanobiological screening accessible, reliable, and cost-effective. The anticipated impact spans faster therapeutic development, reduced reliance on animal models, and improved safety assessment for a broad range of compounds—ultimately benefiting science, industry, and society as a whole.
Our project addresses this unmet need by developing TissMec, a new technology that enables fully automated cultivation, stimulation, and mechanical characterization of human 3D tissues. TissMec builds on an earlier generation of tissue-growth chambers developed under the ERC Consolidator Grant PolarizeMe, which already enable scalable growth and imaging of human muscle tissue. However, current systems cannot measure essential physical tissue functions—such as force generation, stiffness, or viscosity—and they require manual imaging steps that make high-throughput screening impractical.
TissMec introduces a breakthrough solution: a compact, scalable chamber that combines optical fiber–based force detection, piezoelectric actuation, and direct optical access for high-resolution microscopy. This integrated platform allows drug candidates to be tested on human-derived tissues while automatically quantifying how they affect tissue mechanics—an essential marker for safety and efficacy that is currently inaccessible in high-throughput formats. In contrast to existing commercial systems, TissMec can stimulate tissues electrically, apply defined mechanical loads, mimic pathological mechanical environments (such as heart failure or fibrosis), and read out tissue mechanics without requiring a microscope. The system is designed to be compatible with standard multi-well formats, enabling direct integration into widely used industrial screening pipelines.
The expected impact is substantial. By providing early, reliable, and fully automated tests on human tissue, TissMec has the potential to dramatically reduce the number of ineffective or harmful compounds entering animal experiments or clinical trials—thereby lowering development costs, reducing animal use, and accelerating innovation in drug discovery. The technology is relevant not only for pharmaceutical companies but also for academic researchers and chemical safety testing, particularly as European and US policy increasingly encourages alternatives to animal-based testing.
In summary, TissMec introduces a transformative approach to functional 3D tissue screening. By merging tissue engineering, precision mechanics, and automated optical measurement in a single scalable platform, the project aims to make high-content mechanobiological screening accessible, reliable, and cost-effective. The anticipated impact spans faster therapeutic development, reduced reliance on animal models, and improved safety assessment for a broad range of compounds—ultimately benefiting science, industry, and society as a whole.
We moved from the initial muscle chamber design to the next level by integrating an all-optical post-deformation system. This allows mechanical force measurements of contractile muscles without the need for a microscope and fully inside an incubator. Furthermore, we attached a piezo bending element to one of the posts, thereby controlling post bending and thus the strain of the system. In combination with the optical measurement of post bending, we obtain the actively generated stress and the resulting strain of the tissue. We could demonstrate, for the first time, tissue rheology directly in the chamber system, without removing the tissue from the growth chamber or requiring any additional intervention. The main achievements are the implementation of the all-optical readout of post position, the controlled illumination of the posts, the isolation of the 200 V electrical potential applied only millimetres away from the living tissue, and the implementation of force and strain measurements. The main hurdles we had to overcome, besides the high voltage mentioned above, were the calibration of the post system, the elimination of optical and mechanical crosstalk between posts, and the successful cultivation of muscle tissue in the new chamber. The main scientific achievement is the first viscoelastic rheology measurement of engineered muscle tissue.
We have established the proof of concept for the new multifunctional chamber system. The next step is to demonstrate that it can be used in a closed-loop protocol to apply almost arbitrary load conditions and mimic different disease states, including cardiac pathologies. We have carried out a market analysis and contacted initial industrial partners. The intellectual property for this development has been submitted and is currently under evaluation. We have also approached first commercial partners, such as ArtifiCell, the startup company commercializing the initial chamber system on which this project builds. In addition, we contacted NCardia, a drug-screening company, and obtained a clear statement outlining the performance requirements the chamber must meet to become relevant for this partner. All these steps are currently ongoing, and we plan to submit an EIC Transition application next September.
To progress from the Proof-of-Concept stage to a position where we can either transfer the chamber system to an existing company or consider creating a dedicated startup, several further steps are required. First, we need to redesign the chamber system based on the knowledge gained, improving performance and optimizing the layout for future upscaling. Second, we must scale the system to an 8-chamber configuration compatible with a 96-well-plate format. This requirement was emphasized by all potential industrial partners, and we are now preparing to move in this direction. Finally, we need to show that the chamber can measure engineered heart muscle tissue and reliably quantify the effects of well-established drugs in this field.
Our main results so far are the successful creation of a working prototype, its calibration, the resolution of mechanical and optical crosstalk that initially appeared as unforeseen noise, and the first measurement of viscoelastic properties in engineered heart tissue.
To progress from the Proof-of-Concept stage to a position where we can either transfer the chamber system to an existing company or consider creating a dedicated startup, several further steps are required. First, we need to redesign the chamber system based on the knowledge gained, improving performance and optimizing the layout for future upscaling. Second, we must scale the system to an 8-chamber configuration compatible with a 96-well-plate format. This requirement was emphasized by all potential industrial partners, and we are now preparing to move in this direction. Finally, we need to show that the chamber can measure engineered heart muscle tissue and reliably quantify the effects of well-established drugs in this field.
Our main results so far are the successful creation of a working prototype, its calibration, the resolution of mechanical and optical crosstalk that initially appeared as unforeseen noise, and the first measurement of viscoelastic properties in engineered heart tissue.