Continued sustained insulin-releasing PLGA nanoparticles modified 3D-Printed PCL composite scaffolds for osteochondral repair

• We have successfully fabricated the insulin-PLGA/PDA/PCL composite scaffolds. • The scaffolds can provide a slow, sustained release of insulin. • The scaffolds stimulated chondrocytes proliferation and BMSCs differentiation. • The scaffolds enhanced bone and cartilage repair in vivo. Due to the poor ability of self-repair and regeneration, articular cartilage and subchondral bone defects and degradation are still a big problem nowadays. The aim of the present study is to fabricate and investigate a 3D printed polycaprolactone (PCL) scaffold modified by insulin-releasing PLGA nanoparticles for osteochondral repair. The double-emulsion solvent evaporation method is used to fabricate the insulin-coated PLGA nanoparticles, and the physicochemical characterization of the nanoparticles and scaffolds are tested. The cell studies in vitro and animal experiments in vivo are also investigated. The results show the hydrophilicity of the scaffolds is highly improved when coated with polydopamine (PDA), and the insulin release curve of the insulin-PLGA/PDA/PCL scaffolds exhibit a slowly and sustained profile after an initial burst release. The in vitro studies show that the insulin-PLGA/PDA/PCL scaffolds significantly improve the osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) and the proliferation of chondrocytes. And the in vivo studies show that the insulin-PLGA/PDA/PCL scaffolds significantly improve repair of cartilage and subchondral bone after 8- and 12-week implantation in rabbit osteochondral defects. These findings exhibit that the insulin-PLGA/PDA/PCL scaffolds can provide a slowly, sustained release of insulin and may be a promising strategy for osteochondral repair.