Magnesium-oxide-enhanced bone regeneration: 3D-printing of gelatin-coated composite scaffolds with sustained Rosuvastatin release

Abstract

Critical-size bone defects are one of the main challenges in bone tissue regeneration that determines the need to use angiogenic and osteogenic agents. Rosuvastatin (RSV) is a class of cholesterol-lowering drugs with osteogenic potential. Magnesium oxide (MgO) is an angiogenesis component affecting apatite formation. This study aims to evaluate 3D-printed Polycaprolactone/β-tricalcium phosphate/nano-hydroxyapatite/ MgO (PCL/β-TCP/nHA/MgO) scaffolds as a carrier for MgO and RSV in bone regeneration. For this purpose, PCL/β-TCP/nHA/MgO scaffolds were fabricated with a 3D-printing method and coated with gelatin and RSV. The biocompatibility and osteogenicity of scaffolds were examined with MTT, ALP, and Alizarin red staining. Finally, the scaffolds were implanted in a bone defect of rat's calvaria, and tissue regeneration was investigated after 3 months. Our results showed that the simultaneous presence of RSV and MgO improved biocompatibility, wettability, degradation rate, and ALP activity but decreased mechanical strength. PCL/β-TCP/nHA/MgO/gelatin-RSV scaffolds produced sustained release of MgO and RSV within 30 days. CT images showed that PCL/β-TCP/nHA/MgO/gelatin-RSV scaffolds filled approximately 86.83 + 4.9 % of the defects within 3 months and improved angiogenesis, woven bone, and osteogenic genes expression. These results indicate the potential of PCL/β-TCP/nHA/MgO/gelatin-RSV scaffolds as a promising tool for bone regeneration and clinical trials.