Highly Porous 3D Printed Scaffold Incorporated with Graphene Oxide-Merwinite and Coated with IGF1 Loaded Nanofibers for Calvarial Defect Repair

Abstract

Critical-sized calvarial bone defects remain a significant challenge in orthopedic surgery, especially for irregularly shaped bones. Herein, we devised a customizable scaffold using a combination of 3D-printing and salt leaching techniques. Polycaprolactone (PCL), sodium chloride, and a graphene oxide-merwinite (GOM) nanocomposite were 3D-printed and then immersed in water to remove residual salt. Subsequently, gelatin-based electrospun nanofibers incorporating insulin-like growth factor-1 (IGF1) were applied to the PCL-GOM scaffold. The addition of 15% of GOM nanoparticles to the PCL scaffold increased the compressive strength from 2.2 to 3.8 MPa and the elastic modulus from 17.2 to 29.8 MPa. Apatite precipitates were well formed on the fabricated scaffolds after 28 days of immersion in simulated body fluid. Moreover, the scaffold displayed a gradual release of IGF1 over 28 days. The MTT assay demonstrated non-toxicity of scaffolds towards the MG63 cell line. Interestingly, significantly higher expression of Collagen I, RUNX2, and Osteocalcin were observed in qRTPCR results. Following implantation in calvarial bone defect for 8 weeks, the optimal scaffold demonstrated excellent osteogenic behavior and new bone tissue formation. This work presents a promising biomaterial with potential clinical applications for the treatment of irregular critical-sized bone defects.

Graphical Abstract