Development of a novel tool for cell therapies that automates the formation and injection of cell-laden hydrogels directly into tissue

Project Summary Cell-based therapies hold immense potential to revolutionize medicine by offering personalized, curative treatments for patients. However, their efficacy to date has been hampered by challenges in successfully delivering cells to target tissues. Standard-of-care intravenous infusion delivers cells systemically, which works for blood-based diseases, but not for solid tissue diseases; cells become trapped in filtering organs and never reach the target. Injecting liquid cell suspensions directly into tissue does not work well either, as cells experience death and lack of retention within the tissue. A potential solution is to encapsulate the cells in hydrogels, which are 3d structures which can act as protective carriers. Beyond helping cells to survive the injection process, hydrogels can also increase the likelihood that cells engraft within the tissue, as they can be designed to anchor to the extracellular matrix (ECM) in the tissue, or to eventually dissolve, leaving behind cells that have integrated in the ECM. One class of hydrogels in particular - shear-thinning hydrogels - provide a promising mix of mechanical properties for clinical applications. The challenge, however, is that formation and encapsulation of these hydrogels is extremely variable, and manual methods have not been reproducible enough to allow for clinical translation. Cellular Vehicles Inc. is proposing the development of a system to automate and standardize the production of ‘cells in hydrogel’ preparations. Building on our prior success developing the Odyssey System for automation of ‘cells in media’ preparations, we, along with our collaborators at Drexel University, will work together to develop a novel version for this product for cell-laden hydrogel therapies. This project will push forward a novel, automated method to formulate, encapsulate, and inject cell-laden hydrogels with increased consistency, with the goal of eventually improving cell survival and retention in the diseased tissue. The project's aims include developing an automated method for hydrogel mixing, designing a protocol that achieves uniform cell encapsulation, and assessing the success of injection through clinically relevant formats. Successful completion of this project will lead to a Phase II project during which we will advance the scalability and robustness of the technology, aiming to optimize the automated process for larger-scale contexts while ensuring consistently high cell viability and homogenous hydrogel formulations. The Phase II project will include preclinical testing in an animal model to evaluate the safety and capability of the automated cell-laden hydrogel delivery system to inject into tissue. These advancements will position the technology to be submitted to the FDA Class II 510(k) de novo pathway. FDA approval will lead to partnerships with cell therapy developers, and clinical translation. Overall, the outcome of this research will greatly advance the clinical potential of cell-based therapies, particularly for treating solid-tissue diseases.