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

Int J Biol Macromol. 2024 May;266(Pt 1):130995. doi: 10.1016/j.ijbiomac.2024.130995. Epub 2024 Mar 21.

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.

Keywords: 3D-printing; Angiogenesis; Bone tissue engineering; Gelatin; Magnesium oxide; Rosuvastatin.

MeSH terms

  • Animals
  • Bone Regeneration* / drug effects
  • Calcium Phosphates / chemistry
  • Calcium Phosphates / pharmacology
  • Delayed-Action Preparations / pharmacology
  • Drug Liberation
  • Durapatite / chemistry
  • Durapatite / pharmacology
  • Gelatin* / chemistry
  • Magnesium Oxide* / chemistry
  • Magnesium Oxide* / pharmacology
  • Osteogenesis* / drug effects
  • Polyesters / chemistry
  • Printing, Three-Dimensional*
  • Rats
  • Rosuvastatin Calcium* / chemistry
  • Rosuvastatin Calcium* / pharmacology
  • Skull / drug effects
  • Tissue Engineering / methods
  • Tissue Scaffolds* / chemistry

Substances

  • Rosuvastatin Calcium
  • Gelatin
  • Magnesium Oxide
  • Polyesters
  • polycaprolactone
  • beta-tricalcium phosphate
  • Durapatite
  • Delayed-Action Preparations
  • Calcium Phosphates