Engineering alginate-based injectable hydrogels combined with bioactive polymers for targeted plasma-derived...

Reactive Oxygen and Nitrogen Species (RONS) in biological systems display hormetic effects, capable of either promoting cell regenerative effects or inducing cell death. Recently, hydrogels have emerged as a promising delivery platform for RONS generated from Cold Atmospheric Plasmas (CAP), known as Plasma-Treated Hydrogels (PTH). PTH have been proposed as an alternative therapy to conventional cancer treatments, offering reduced side effects through the controlled and localized delivery of plasma-derived RONS. In this work, we have developed alginate-based PTH with dual therapeutic action provided by plasma-derived RONS acting as selective anticancer agents for osteosarcoma treatment, and biomolecules (hyaluronic acid and gelatin) to promote stem cell-mediated bone regeneration. For this purpose, we designed a novel manufacturing process to maximize the load of plasma-derived RONS within the PTH. Then, we assessed the PTH bioactivity on osteosarcoma MG-63 cells, and human mesenchymal stem cells (hMSCs). The results showed that the PTH composed of 0.25 % alginate +1 % hyaluronic acid is the most promising formulation in osteosarcoma treatment, showing a dual-action bioactivity as a selective cytotoxic anticancer agent, and as promoter of the proliferation and osteogenic differentiation of hMSCs. These findings provide strong evidence of the significant potential of PTH in the oncological field.