Methacrylated gellan gum and hyaluronic acid hydrogel blends for image-guided neurointerventions

Abstract

Cell-based therapies deliveredviaintrathecal injection are considered as one of the most promisingsolutions for the treatment of amyotrophic lateral sclerosis (ALS). Herein, injectable manganese-basedbiocompatible hydrogel blends were developed, that can allow image-guided cell delivery. Thehydrogels can also provide physical support for cells during injection, and at the intrathecal space aftertransplantation, while assuring cell survival. In this regard, different formulations of methacrylated gellangum/hyaluronic acid hydrogel blends (GG-MA/HA) were considered as a vehicle for cell delivery. Thehydrogels blends were supplemented with paramagnetic Mn2+to allow a real-time monitorization ofhydrogel depositionvia T1-weighted magnetic resonance imaging (MRI). The developed hydrogels wereeasily extruded and formed a stable fiber upon injection into the cerebrospinal fluid. Hydrogels preparedwith a 75 : 25 GG-MA to HA ratio supplemented with MnCl2at 0.1 mM showed controlled hydrogeldegradation, suitable permeability, and a distinct MRI signalin vitroandin vivo. Additionally, human-derived adipose stem cells encapsulated in 75 : 25 GG-MA/HA hydrogels remained viable for up to14 days of culturein vitro. Therefore, the engineered hydrogels can be an excellent tool for injectableimage-guided cell delivery approaches.