Study on the effect of sustained -release icariin-loaded Graphene oxide-hydrogel composite scaffold on bone defect repair

Abstract In orthopedic treatment, long-term nonunion of bone defects has always been a significant issue. As bone graft materials, tetra-armed polyethylene glycol (Tetra-PEG) hydrogel scaffolds are anticipated to address this issue due to their extracellular matrix (ECM)-like structure. However, poor osteoinductivity and cell adhesion after implantation restricted its clinical application in bone tissue engineering. Herein, graphene oxide (GO) loaded with icariin (ICA) was loaded into the Tetra-PEG hydrogel semi-interpenetrating network composite gel by in situ composite approach, and silk fibroin (SF) was incorporated to create a new organic–inorganic composite hydrogel scaffold (PNSG-ICA) to investigate the controlled drug release characteristics and osteogenic properties. The experiments of this study demonstrate that PNSG-ICA scaffolds can effectively encapsulate and release ICA over a period of 12 days. The scaffolds exhibited interconnected porous microarchitectures, satisfactory mechanical properties, appropriate degradation characteristics, and excellent biocompatibility. In vitro analyses indicated that ICA-doped hydrogels significantly enhanced the osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs), as demonstrated by alkaline phosphatase and alizarin red staining, as well as qRT-PCR assessments. Moreover, in vivo investigations revealed that the ICA sustained-release system significantly enhanced the regeneration of bone defects mediated by rBMSCs in situ , as evidenced by mouse calvarial bone defect models. In summary, we envision that the prolonged release of ICA from PNSG-ICA scaffolds may become a new strategy for the clinical treatment of bone defects.