Direct osteogenesis and immunomodulation dual function via sustained release of naringin from the polymer scaffold

Abstract

Many traditional Chinese medicine monomers, such as naringin (NG), can regulate the local immune microenvironment to benefit osteogenesis. However, the rapid release of NG from scaffolds severely influences the osteogenesis-promoting effect. Herein, NG was loaded into mesoporous bioglass (MBG) to achieve sustained release through physical adsorption and the barrier role of mesoporous channels, then MBG loaded with NG was added to poly(L-lactic acid) (PLLA) to fabricate composite scaffolds by selective laser sintering (SLS) technology. The results showed that the NG-MBG/PLLA scaffolds could continuously and slowly release NG for 14 days compared with NG/PLLA scaffolds, and the cumulative release amount for the NG-MBG/PLLA scaffolds was 44.26%. In addition, the NG-MBG/PLLA scaffolds can promote the proliferation and osteogenesis differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs). Meanwhile, the composite scaffolds decreased the reactive oxygen species (ROS) level of RAW264.7 under the stimulation of lipopolysaccharide (LPS) and significantly suppressed interleukin-6 (IL-6) and enhanced arginase-1 (Arg-1) protein expressions. Moreover, calcium nodule and alkaline phosphatase production of mBMSCs in a macrophage-conditioned medium for the NG-MBG/PLLA group also evidently increased compared with the PLLA and MBG/PLLA groups. These NG sustained-release composite scaffolds with osteo-immunomodulation function have great application prospects in the clinic.