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

ABSTRACT： Many traditional Chinese medicines monomers, such as naringin (NG), can regulate the local immune microenvironment to benefit osteogenesis. However, the rapid release of NG in 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 slow-release NG for 14 days compared with the NG/PLLA scaffolds, 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 declined 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 nodules and alkaline phosphatase productions of mBMSCs under macrophages-conditioned medium for the NG-MBG/PLLA group also evidently increased compared with the PLLA and MBG/PLLA groups. The NG sustained-released composite scaffolds with osteo-immunomodulation function have a great application prospect in the clinic.