Periodic Reporting for period 1 - L-Cell (Light-reconfigurable substrate for cell cultures)
Reporting period: 2022-08-01 to 2024-01-31
Pharmaceutical companies invest approximately $2 billion in research and development (R&D) to bring a new therapeutic entity to the market. However, the failure rate of new molecular entities during clinical phase testing is alarmingly high, with over 90% not making the cut. The primary culprit behind this low success rate is the inadequacy of cellular models used in in vitro studies, which fall short in replicating the complex conditions of the human body. In contrast, in vivo studies, which examine the cellular microenvironment or cellular niche, are good at regulating various cellular functions and are particularly effective for investigating chronic and systemic effects. Despite their clinical relevance, in vivo tests are not only costly and time-intensive but also raise ethical and regulatory concerns. On the other hand, in vitro tests offer advantages such as speed, repeatability, cost-effectiveness, simplicity, superior quality control, and minimal material requirements. This stark contrast underscores the pressing need for more sophisticated cell-based models that can closely emulate the dynamic in vivo conditions within in vitro cell cultures.
Currently, standard practice involves culturing cells in petri dishes, flasks, and plates, which lack the simulation of a natural cellular niche. A significant limitation of these methods is the absence of surface topography, failing to accurately represent the cellular microenvironment within the human body. Moreover, adherent cells in the human body are in a state of constant change, modifying and interacting with their microenvironment. This interaction fosters a dynamic extracellular environment that is challenging to replicate in vitro. Although engineering techniques have been employed to create micropatterned cell culture plates, these often feature abrupt topographical characteristics rather than the smooth contours typical of the cellular environment. Furthermore, these models are hindered by their inability to reconfigure or dynamically alter the surface.
Over recent years, our team has developed a platform that addresses the critical physiological parameter often missing in industrial in vitro drug discovery processes: mechanical stimulation. The L-Cell platform is an innovative light-responsive cell culturing plate designed to undergo repeated reshaping at the micrometer level using visible light. This feature allows to simulate the physiological stress experienced by cells in vivo, within an in vitro setting. This technological leap holds the promise of improving current in vitro drug testing methods and disease models-in-a-dish.
Currently, standard practice involves culturing cells in petri dishes, flasks, and plates, which lack the simulation of a natural cellular niche. A significant limitation of these methods is the absence of surface topography, failing to accurately represent the cellular microenvironment within the human body. Moreover, adherent cells in the human body are in a state of constant change, modifying and interacting with their microenvironment. This interaction fosters a dynamic extracellular environment that is challenging to replicate in vitro. Although engineering techniques have been employed to create micropatterned cell culture plates, these often feature abrupt topographical characteristics rather than the smooth contours typical of the cellular environment. Furthermore, these models are hindered by their inability to reconfigure or dynamically alter the surface.
Over recent years, our team has developed a platform that addresses the critical physiological parameter often missing in industrial in vitro drug discovery processes: mechanical stimulation. The L-Cell platform is an innovative light-responsive cell culturing plate designed to undergo repeated reshaping at the micrometer level using visible light. This feature allows to simulate the physiological stress experienced by cells in vivo, within an in vitro setting. This technological leap holds the promise of improving current in vitro drug testing methods and disease models-in-a-dish.
Our L-Cell reconfigurable light-responsive culture plates can be used as drop-in solution to replace current cell culture substrates. The L-Cell project aimed at offering a new tool for building better in vitro models, with 1) tailored substrate with pre-defined and constructed topographies, 2) possibility to create free-form topographical patterns by the end-user and 3) the possibility to dynamically change these topographies during the experiments.
The project's technical and scientific activities were strategically selected to fulfil the predefined goals. Initially, we identified and tested materials suitable for the concept device's fabrication and refined the manufacturing process for optimal results. We successfully created an 8-well concept device and pinpointed technologies to scale up production and enlarge the device size. We conducted multiple inscription erasure cycles using a confocal microscope and confirmed the viability of cell cultures with various cell types, including epithelial cells, fibroblasts, and cardiomyocytes, with additional cell lines currently under investigation. Notably, we achieved extended culture periods with epithelial cells, maintaining them for up to 10 weeks. Commercially, we have engaged with numerous prospective end-users through semi-structured interviews and studied the relevant market with a subcontractor's assistance. Our active discussions with interested parties and stakeholders at key networking events have been fruitful. We have filed patents in five different countries (US, CA, EU, JP, CH) and conducted a freedom-to-operate analysis, which confirmed no infringement risks. These findings will be instrumental in strategizing our commercialization path forward.
The project's technical and scientific activities were strategically selected to fulfil the predefined goals. Initially, we identified and tested materials suitable for the concept device's fabrication and refined the manufacturing process for optimal results. We successfully created an 8-well concept device and pinpointed technologies to scale up production and enlarge the device size. We conducted multiple inscription erasure cycles using a confocal microscope and confirmed the viability of cell cultures with various cell types, including epithelial cells, fibroblasts, and cardiomyocytes, with additional cell lines currently under investigation. Notably, we achieved extended culture periods with epithelial cells, maintaining them for up to 10 weeks. Commercially, we have engaged with numerous prospective end-users through semi-structured interviews and studied the relevant market with a subcontractor's assistance. Our active discussions with interested parties and stakeholders at key networking events have been fruitful. We have filed patents in five different countries (US, CA, EU, JP, CH) and conducted a freedom-to-operate analysis, which confirmed no infringement risks. These findings will be instrumental in strategizing our commercialization path forward.
During the L-Cell project, we have successfully secured funding to continue exploring further opportunities for uptake and success. Additionally, we have filed a patent, identified potential markets, and engaged in discussions with several key stakeholders. Despite this progress, we still need to define an appropriate go-to-market strategy and prepare a comprehensive business plan.