Injectable thermosensitive hydrogels with enhanced mechanical properties for cell therapy

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Injectable hydrogels are increasingly used for minimally invasive treatment of diseases, especially in combination with cell seeding, because they can ensure appropriate cell localization, retention and survival. Ideally, an injectable gel should have relatively low viscosity before and during injection but gel rapidly and exhibit high mechanical strength after being delivered, to ensure matrix cohesion and tolerance to in vivo stresses. However, there is a lack of injectable material that combines these qualities with excellent cell compatibility. Our team recently developed a method for preparing high-strength, fast-thermogelling chitosan (CH)-based hydrogels using new gelation agents that may solve this issue. ******The objectives of this 5-year research program are to design, optimize and characterize these thermosensitive hydrogels for use as injectable scaffolds, especially in cell therapy, and to explore their potential for additive manufacturing of tissue using 3D bioprinting. ***We will first study how the gelation kinetic, mechanical properties and porosity are influenced by gel composition, to better understand why CH gels containing sodium hydrogen carbonate (SHC) present much higher mechanical properties and to be able to tailor a gel's properties as needed for a specific application. We will then evaluate their suitability for encapsulation of human mesenchymal stem cells (MSCs) and T lymphocytes, both of which hold great promise in cell therapy. MSC survival and therapeutic efficiency will be optimized by two different approaches: a) pharmacological preconditioning of cells before encapsulation and b) design of bioactive scaffolds containing chondroitin sulfate and growth factors. Finally we will leverage these customizable hydrogels for use in bioprinting, which makes it possible to create complex and heterogeneous 3D structures mimicking living tissues, with potential applications for tissue engineering, drug screening and toxicology. ******A dozen students will be involved in this research program, including 2 PhDs, 3 Masters and 2 post-doctoral students. While we do not target any specific clinical application for this grant, our work will contribute knowledge and data toward the development of minimally invasive treatments with increased efficacy and reduced risk (thanks to more local delivery), thereby reducing costs and morbidity rates. Thus, in the long term, benefits for Canadian health and industry are also expected from our research results and the training of high-quality HQP in this strategic field.