Cell-laden and Injectable Hydrogels for Ischemic Stroke recovery

Stroke survivors suffer serious impairments, as paralysis and difficulties in basic functions, affecting their independence and consequently the quality of life. Current treatments have a narrow therapeutic window and unsatisfying results regarding the repair of lost tissue[1]. Key aspects for brain regeneration are the preservation of surviving neuro-cells and promotion of endogenous repair mechanisms[2]. The present work will focus on Mesenchymal Stem Cells (MSCs) transplantation, encapsulated within injectable hydrogels (blends of thiolated Hyaluronic Acid[3] and methacrylated Gellan Gum[4]), containing Mn2+. The cell-laden hydrogels will provide the conditions for neural repair (trophic support and/or cell replacement), while the Mn2+ cations will allow MRI imaging of the scaffolds’ performance. Growth-factor loaded Nanoparticles will be added to the cell-laden hydrogels, to support both host and transplanted cells. The scaffolds will be tested in an animal model of stroke, originated by fast dissolving microparticles (MPs), containing Mn2+ or iron-oxide. The produced MPs will be administrated in the carotid/pharyngeal artery, to produce an artificial brain clog for 30 to 60 minutes, which will then disintegrate, originating a stroke-like brain injury. The MPs were injected through catheters of two sizes (mouse and pig size) and maintained their shape without clogging the catheter. The MRI analysis showed that both Mn2+ and Iron-oxide are good candidates for MRI contrasts, as from 0.5 to 2 mg/ml the MPs produced a signal. However, the Mn2+ diffuses more quickly than expected, so future work will consist on optimizing its incorporation. Future work also includes the analysis of the hydrogel’s mechanical properties and their biocompatibility with MSCs.