Thermoresponsive Copolypeptide Hydrogel Vehicles for Central Nervous System Cell Delivery

Biomaterial vehicles have the potential to facilitate cell transplantation in the central nervous system (CNS). We have previously shown that highly tunable ionic diblock copolypeptide hydrogels (DCH) can provide sustained release of hydrophilic and hydrophobic molecules in the CNS. Here, we show that recently developed nonionic and thermoresponsive DCH, called DCHT, exhibit excellent cytocompatibility. Neural stem cell (NSC) suspensions in DCHT were easily injected as liquids at room temperature. DCHT with a viscosity tuned to prevent cell sedimentation and clumping significantly through injection cannulae. At body temperature, DCHT self-assembled into hydrogels with a stiffness tuned to that of CNS tissue. After injection in vivo, DCHT significantly increased by 3-fold the survival of NSC grafted into a healthy CNS. In an injured CNS, NSC injected as suspensions in DCHT distributed well in non-neural lesion cores, integrated with healthy neural cells at lesion perimeters, and supported regrowing host nerve fibers. Our findings show that nonionic DCHT have numerous advantageous properties that make them useful tools for in vivo delivery of cells and molecules in the CNS for experimental investigations and potential therapeutic strategies.