CNS regeneration after Ischemic Stroke: Injectable Multifunctional Hydrogels

Stroke is a leading cause of death worldwide, with a high disability rate in surviving patients. Ischemic stroke is an obstruction of brain’s vascular structures, lack of blood supply and generalised cell death, together with an inflammatory reaction that further exacerbates the damage. Depending on vein, stroke’s violence and time of treatment, patients can partly recover from stroke, whilst having neuronal impairments for life. Current treatments rely on clot/obstruction lysing or surgical retrieval, but only benefits some patients since the treatment must be performed a few hours after the stroke, leaving the rest of patients only with palliative care. There is a need for a novel regenerative therapy that restores brain function and promotes plasticity in the newly formed tissue. Stem cell-based therapies offer great potential for trophic support or cell replacement, but have low engraftment rate upon transplantation [1]. Biomaterials combined with molecules/cells can be utilized as carriers that fill the lesion’s cavity (in situ gelification), protect transplanted cells from body clearance/hostile environment and promote their interaction with host cells. Natural hydrogels have inherent biological/chemical cues that produce specific cell responses (increased adhesion/proliferation) and allow to tailor their biological/physicochemical properties (harder/softer hydrogels, higher/lower degradation) to our purpose. Moreover, their 3D environment mimics brain tissue, supports cells’ engraftment/survival, are enzymatically/hydrolytically degraded upon new tissue formation and can be minimally invasive administrated (injected). Neurotrophic/angiogenic factors administration ameliorates the hostile microenvironment and promotes neural/vascular regeneration, their incorporation into Nanoparticles (NPs) increases stability and protects from enzymatic degradation, prolonging their therapeutic effect without needing systemic administrations [2]. Having this in mind, the proposed strategy focus on producing natural-based hydrogels and assessing their physicochemical properties (mechanical properties, viscosity, gelation time, permeability, weight loss/swelling and degradation rates). Afterwards, the produced hydrogels will be combined with Mesenchymal Stem Cells/Neural Stem Cells and/or carboxymethylchitosan/polyamidoamine-NPs (previously loaded with relevant growth factors), to obtain an injectable multifunctional hydrogel that will modulate the lesion’s microenvironment and repair the stroke damage.