A guest-host hydrogel for neural tissue engineering applications

Worldwide, neurological injuries and disorders are a leading cause of disability, yet there are limited treatment options that address the underlying mechanisms associated with these injuries and diseases. Injectable hydrogels may serve as a neural tissue engineering platform to promote tissue healing and neural regeneration via minimally invasive delivery and providing physical and chemical support for damaged tissue. In this study, an injectable hyaluronic acid (HA) hydrogel was developed based on guest-host interactions between cyclodextrin and adamantane groups. Rheological characterization of the hydrogel confirmed that altering the HA content optimized material properties to match those of endogenous brain tissue. In addition, the shear-thinning and self-healing properties necessary for the injectability of the hydrogel were verified. In vitro toxicity testing via a lactate dehydrogenase (LDH) assay with primary mouse astrocytes established the biocompatibility of the hydrogel prior to in vivo studies. Importantly, intracortical injections of the hydrogel in mice elicited a modest inflammatory response comparable to a control polymer thereby indicating that this HA hydrogel may serve as a platform for future neural tissue engineering systems.