Impact of 1,25-dihydroxyvitamin D3 PLGA-nanoparticles/chitosan hydrogel on osteoimmunomodulation

Severe bone defects that extend beyond a critical size do not heal on their own, increasing the risk of complications and leading to poor outcomes for patients. Healing is a highly coordinated and complex process in which immune cells have an important function making the design and preparation of biomaterials with immunomodulatory functions an important new therapeutic strategy. 1,25-dihydroxyvitamin D3 (VD3) is crucial for bone metabolism and immune regulation. For post-defect bone regeneration, we developed a drug delivery system (DDS) based on chitosan (CS) and nanoparticles (NPs) to sustain the release effect of VD3 and desirable biological characteristics. The hydrogel system was physically characterized and confirmed to have good mechanical strength, degradation rate, and drug release rate. In vitro experiments showed that the cells had good biological activity when the hydrogel was co-cultured with MC3T3-E1 and RAW264.7. The high expression of ARG-1 and low expression of iNOS in macrophages confirmed that VD3-NPs/CS-GP hydrogel transformed lipopolysaccharide-induced M1 macrophages into M2 macrophages. Alkaline phosphatase and alizarin red staining showed that VD3-NPs/CS-GP hydrogel promoted osteogenic differentiation under inflammatory conditions. In conclusion, VD3-NPs/CS-GP hydrogel with synergistic anti-inflammatory and pro-osteogenic differentiation effects may serve as a potential immunomodulatory biomaterial for bone repair and regeneration in cases of bone defects.