Multifunctional Scaffolds for Brain Repair Following Ischemic Stroke

Stroke is a leading cause of death worldwide and increased numbers are being reported each year. Stroke impairs surviving patients’ life and current treatments are scarce, with a narrow therapeutic window. Providing the conditions for brain repair on lesion sites, protecting remaining neurons and stimulating endogenous mechanisms are key targets for brain recovery/regeneration following stroke. The present work focus on stem cell transplantation (NSCs and MSCs), for trophic support and cell replacement, to be encapsulated within Mn²⁺ hydrogels (blends of thiolated Hyaluronic Acid and methacrylated Gellan Gum) to promote transplanted/host cells’ survival and proliferation. Additionally, growth factor-loaded nanoparticles will be blended on the hydrogel, for their controlled release on the lesion site. The incorporation of Mn²⁺ into the hydrogels will allow the biomaterials’ imaging during implantation and throughout the experiment. The goal is to provide a suitable environment for neural regeneration following stroke, while allowing the imaging of scaffolds through MRI-based techniques. The functionalization of the Hyaluronic Acid (HA) was successful, as proved by NMR analysis and physical assessment (in basic pH the hydrogel reacts with oxygen and self-crosslinks without needing the addition of other compounds). The thiolated HA was incubated for 4 hours with murine erythrocytes and did not produce haemolysis (bursting of the erythrocytes) in any of the concentrations (0.5%, 1% and 1.5%), as established by the American Society for Testing and Materials (ASTM) haemolytic index. The future work will consist in evaluating the biocompatibility of the produced hydrogel, using NSCs and MSCs cultures.