Blended, crosslinked alginate-methylcellulose hydrogels for encapsulation and delivery of olfactory ensheathing cells

Abstract

Transplantation of olfactory ensheathing cells (OECs) is a promising treatment option for spinal cord injuries. Functional outcomes however are highly variable, creating the need for improved transplantation and cell delivery methods. Low OEC survival post-transplantation is primarily due to the absence of a 3D cell delivery system and scaffold, capable of supporting cell structure and migration at the injury site. A 3D cell delivery system, particularly a hydrogel-based system, could ensure viability, functionality and therapeutic activity of transplanted OECs. This study aimed to develop a blended cell delivery system based on alginate (AL) and methylcellulose (MC), capable of encapsulating and delivering OECs over a 20-day period. Three different 1 w/v% ALMC ratios (1:0.5, 1:1 and 1:2) were investigated, which were compared to 1 w/v% AL (control). By chemically crosslinking the pre-gels with CaCl2, OECs were encapsulated within the AL and blended ALMC beads. These beads were then used to study encapsulation efficiency (EE%) and cell delivery, and were further examined with histology and immunocytochemistry. Results showed that the blended ALMC hydrogel can be used to encapsulate OECs, with the highest EE% and cell proliferation exhibited by the 1:0.5 and 1:2 ALMC beads. The 1:1 and 1:2 ALMC beads showed the highest percentage viability for delivered/released and proliferating OECs. Examination of delivered/released OECs concluded that the cell morphology was characteristic of native bipolar OECs, which expressed signature glial markers, demonstrating maintenance of phenotype. In summary, the findings here support the efficacy and use of blended ALMC hydrogels as a cell delivery system.