Injectable gellan gum/lignocellulose nanofibrils hydrogels enriched with melatonin loaded forsterite nanoparticles for cartilage tissue engineering: Fabrication, characterization and cell culture studies

Injectable hydrogels based on natural polysaccharides have attracted considerable attention in cartilage tissue engineering, especially those reinforced with mineral nanofilers carrying drug molecules. Here, a novel injectable hydrogel based on gellan gum (GG)/lignocellulose nanofibrils (LG(NF)) composite enriched with melatonin (MEL) loaded forsterite (FS) nanoparticles (FS-MEL) was developed to yield enhanced mechanical and biological properties of the hydrogels. Gelation time and temperature were determined for different hydrogel formulation containing 1-5 w/v% LG(NF) and 0.1-0.3 w/v% FS-MEL. The injectability WA proved the ease of injection of the developed hydrogels. Degradation rate and swelling degree of developed hydrogel were evaluated to determine the effect of LG(NF) and FS on hydrogel behaviour. Results of mechanical characterization showed that the compressive modulus and strength of GG hydrogels were improved by incorporation of LG(NF) and FS. The results of MEL release study in PBS revealed that MEL showed more sustained release from the hydrogel compared to FS nanoparticles. Cell-hydrogels interaction was evaluated by culturing chondrocyte cells. Results exhibited higher cell adhesion, proliferation and gene expression on GG/LG(NF)/FS-MEL hydrogel compared to GG/LG(NF) and GG/LG(NF)/FS, which can be attributed to the synergic effect of FS and MEL. Overall results demonstrated that the developed GG/LG(NF)/FS-MEL hydrogels can be offered as promising materials for cartilage regeneration applications.