Hybrid GelMA-HAMA hydrogels incorporating dexamethasone-loaded PLGA nanoparticles for controlled release and osteogenic differentiation for bone tissue regeneration

• Characterization of methacrylated gelatin (GelMA)/ hyaluronic acid (HAMA) hydrogels. • A single emulsion synthesized dexamethasone-loaded poly(lacticco-glycolic acid) nanoparticles (DEX-PLGA NPs). • 2. The DEX-PLGA NPs were incorporated into the polymeric hydrogels to achieve a controlled and sustained drug release. • The physicochemical properties of the NP-loaded hydrogels were not affected by the incorporation of DEX- PLGA NPs. • In vitro studies showed that these hybrid hydrogels are biocompatible and present excellent cell adhesion, proliferation, and differentiation properties. • The sustained release of dexamethasone ensures the progressive osteogenic differentiation of adipose-derived mesenchymal stem cells (adMSC) within the scaffold The development of novel approaches to bone regeneration remains a challenge in medicine. For such, the control release of biochemical factors appears key to successfully regulate the regeneration process. In this work, the characterization of methacrylated gelatin (GelMA)-hyaluronic acid (HAMA) hydrogels that incorporated dexamethasone-loaded poly(lactic-co-glycolic acid) nanoparticles (DEX-PLGA NPs) was explored as potential scaffolds for bone tissue regeneration. The DEX-PLGA NPs were synthesized and incorporated into the polymeric hydrogels to achieve a controlled and sustained release of the drug in order to ensure the progressive osteogenic differentiation of adipose-derived mesenchymal stem cells (adMSC) within the scaffold. The physicochemical properties of the NP-loaded hydrogels were not affected by the incorporation of DEX-PLGA NPs. In vitro studies demonstrated that these hybrid hydrogels are biocompatible and presented excellent cell adhesion, proliferation, and differentiation properties promoted by the sustained release of dexamethasone as observed, for example, by the alkaline phosphatase (ALP) assay, which confirmed large concentrations of phosphate ions after the first 14 days of incubation. Furthermore, Alizarin Red S staining corroborated a good mineralization, indicative of effective bone matrix formation.