Stroke is one of the most debilitating neurological disorders worldwide. The most common type is ischemicstroke, characterized by an obstruction of the brain’s vascular structures, resulting in a lack of blood supply tothe affected area. At a cellular level, neuronal cells start to die and release inflammatory or apoptotic factorsthat further exacerbate the damage cascade. In the end, a fluid-filled cavity is left, surrounded by a glial scar,which acts as a barrier for neural recovery. Current treatment includes reperfusion via intravenousthrombolysis for clot removal but is often ineffective and might result in hemorrhagic complications, besidesbeing limited by a narrow therapeutic time window.

Crucial targets for the successful repair of an infarcted brain involve ameliorating the harsh lesion siteenvironment and protecting and stimulating endogenous cells. Mesenchymal Stem Cells (MSCs) are known tosecrete numerous beneficial molecules such as anti-inflammatory, neurotrophic, and angiogenic factors andtheir therapeutic use in CNS pathologies has shown promising results, leading to functional improvementsfollowing injury. Nonetheless, their low survival and ineffective engraftment following transplantation aremajor hurdles regarding clinical applications.

Tissue engineering strategies using biocompatible hydrogels can overcome this issue by providing bothmechanical support and more permissive conditions for cell survival/differentiation. Mn2+ will be incorporatedinto the produced hydrogels, allowing its imaging and tracking, through a magnetic resonance imaging (MRI)-based approach. However, Mn2+ in its free form has a short half-life and is easily cleared from the body, whichlimits its application in the long term. Therefore, we attached the Mn2+ to carboxymethyl chitosan dendrimers(CMCht/PAMAM-Mn) that allowed its release in a prolonged manner.

The current work aims to develop a hybrid hydrogel to improve the engraftment and survival of transplantedcells while providing structural support for endogenous cells. Moreover, incorporating Mn2+-based dendrimersinto the hydrogels will allow their imaging and tracking throughout time, giving insight into the biomaterials’behavior in vivo.