Fabrication of 3D-printed scaffolds loaded with gallium acetylacetonate for potential application in osteoclastic bone resorption

Pharm Dev Technol. 2024 Apr;29(4):339-352. doi: 10.1080/10837450.2024.2332459. Epub 2024 Mar 22.

Abstract

We recently reported the potential of a new gallium compound, gallium acetylacetonate (GaAcAc) in combating osteoclastic bone resorption through inhibition of osteoclast differentiation and function. Herein, we focused on 3D-printed polylactic acid scaffolds that were loaded with GaAcAc and investigated the impact of scaffold pretreatment with polydopamine (PDA) or sodium hydroxide (NaOH). We observed a remarkable increase in scaffold hydrophilicity with PDA or NaOH pretreatment while biocompatibility and in vitro degradation were not affected. NaOH-pretreated scaffolds showed the highest amount of GaAcAc loading when compared to other scaffolds (p < 0.05). NaOH-pretreated scaffolds with GaAcAc loading showed effective reduction of osteoclast counts and size. The trend was supported by suppression of key osteoclast differentiation markers such as NFAT2, c-Fos, TRAF6, & TRAP. All GaAcAc-loaded scaffolds, regardless of surface pretreatment, were effective in inhibiting osteoclast function as evidenced by reduction in the number of resorptive pits in bovine cortical bone slices (p < 0.01). The suppression of osteoclast function according to the type of scaffold followed the ranking: GaAcAc loading without surface pretreatment > GaAcAc loading with NaOH pretreatment > GaAcAc loading with PDA pretreatment. Additional studies will be needed to fully elucidate the impact of surface pretreatment on the efficacy and safety of GaAcAc-loaded 3D-printed scaffolds.

Keywords: Osteoclasts; fused deposition; gallium; osteoblasts; polylactic acid; three-dimensional printing.

MeSH terms

  • Animals
  • Bone Resorption* / drug therapy
  • Cattle
  • Cell Differentiation / drug effects
  • Gallium / chemistry
  • Gallium / pharmacology
  • Mice
  • Osteoclasts* / drug effects
  • Pentanones / administration & dosage
  • Pentanones / chemistry
  • Pentanones / pharmacology
  • Polyesters / chemistry
  • Printing, Three-Dimensional*
  • Sodium Hydroxide
  • Tissue Scaffolds* / chemistry

Substances

  • Polyesters
  • poly(lactide)
  • Gallium
  • Pentanones
  • Sodium Hydroxide