Injectable chitosan/maltodextrin/microcrystalline cellulose hydrogels loaded with melatonin for intervertebral disc regeneration

Abstract

Intervertebral discs have limited regenerative capacity despite their high susceptibility to age-related degeneration. Conventional treatments primarily manage symptoms and rarely restore function. Recent research focuses on injectable hydrogel systems for disc regeneration. In this study, an injectable melatonin-loaded hydrogel composed of chitosan (CS), oxidized maltodextrin (ox-MD), and oxidized microcrystalline cellulose (ox-MCC) was developed. Incorporation of MCC markedly reduced gelation time-from 33 s at the lowest concentration (0.125 %) to 12 s at the highest (0.5 %). At the highest MCC content, hydrogels also retained up to 75 % of their weights in degradation studies, compared with 40 % in MCC-free formulations. Increasing ox-MCC levels enhanced the mechanical properties, yielding approximately a six-fold increase in Young's modulus. Melatonin release reached 35.29 % from MCC-containing hydrogels and 26.65 % from hydrogels without MCC. Experiments with nucleus pulposus (NP) cells isolated from bovine vertebrae showed that all hydrogel groups were non-toxic, and melatonin-loaded hydrogels further supported cell proliferation. Moreover, all hydrogels significantly increased glycosaminoglycan synthesis by the cells by day 14, with the melatonin-loaded formulation showing the highest levels. Overall, melatonin-loaded hydrogels demonstrate strong potential for intervertebral disc regeneration.