Objective: To fabricate and test a 3D-printed PCL scaffold incorporating IGF-1 loaded PLGA nanoparticles for cartilage tissue engineering.Methods: IGF-1 loaded PLGA nanoparticles were produced by the double-emulsion method, and were incorporated onto 3D printed PCL scaffolds via PDA. Particle size, loading effciency (LE) and encapsulation effciency (EE) of the nanoparticles were examined. SEM, pore size, porosity, compression testing, contact angle, IGF-1 release kinetics of the composite

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... lds were also determined. For cell culture studies, CCK-8, Live/dead, MTT, GAG content and expression level of chondrocytes specific genes and HIF-1α were also tested.Results: There was no difference of the nanoparticle size. And the LE and EE of IGF-1 in PLGA nanoparticles was about 5.53%±0.12% and 61.26%±2.71%, respectively. There was a slower, sustained release for all drug-loaded nanoparticles PLGA/PDA/PCL scaffolds. There was no difference of pore size, porosity, compressive strength of each scaffold. The contact angles PCL scaffolds were significant decreased when coated with PDA and PLGA nanoparticales. (P < 0.05) Live/dead staining showed more cells attached to the IGF-1 PLGA/PDA/PCL scaffolds. The CCK-8 and MTT assay showed higher cell proliferation and better biocompatibility of the IGF-1 PLGA/PDA/PCL scaffolds. (P < 0.05) GAG content, chondrogenic gene expression level of SOX-9, COL-II, N-cadh, ACAN, and HIF pathway related gene(HIF-1α) were significantly higher in IGF-1 PLGA/PDA/PCL scaffolds on days 7 and 14 compared to other groups. (P < 0.05)Conclusions: IGF-1 PLGA/PDA/PCL scaffolds may be a better method for sustained IGF-1 administration and a promising scaffold for cartilage tissue engineering.