Curcumin encapsulated polylactic acid nanoparticles embedded in alginate/gelatin bioinks for in situ immunoregulation: Characterization and biological assessment

Curcumin is a known naturally occurring anti-inflammatory agent derived from turmeric, and it is commonly  used as a herbal food supplement. Here, in order to overcome the inherent hydrophobicity of curcumin (Cur),  polylactic acid (PLA) nanoparticles (NPs) were synthesised using a solvent evaporation, and an oil-in-water  emulsion method used to encapsulate curcumin. Polymeric NPs also offer the ability to control rate of drug  release. The newly synthesised NPs were analysed using a scanning electron microscope (SEM), where results  show the NPs range from 50 to 250 nm. NPs containing graded amounts of curcumin (0 %, 0.5 %, and 2 %) were  added to cultures of NIH3T3 fibroblast cells for cytotoxicity evaluation using the Alamar Blue assay. Then, the  curcumin NPs were incorporated into an alginate/gelatin solution, prior to crosslinking using a calcium chloride solution (200 nM). These hydrogels were then characterised with respect to their chemical, mechanical and rheological properties. Following hydrogel optimization, hydrogels loaded with NP containing 2 % curcumin  were selected as a candidate as a bioink for three-dimensional (3D) printing. The biological assessment for these bioinks/hydrogels were conducted using THP-1 cells, a human monocytic cell line. Cell viability and immunomodulation were evaluated using lactate dehydrogenase (LHD) and a tumour necrosis factor alpha (TNF-α)  enzyme-linked immunosorbent (ELISA) assay, respectively. Results show that the hydrogels were cytocompatible  and supressed the production of TNF-α. These bioactive hydrogels are printable, supress immune cell activation  and inflammation showing immense potential for the fabrication of tissue engineering constructs.