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

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.

Graphical Abstract

Keywords:

• Osteoclasts
• osteoblasts
• gallium
• three-dimensional printing
• fused deposition
• polylactic acid

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Evin Hessel, Pratyusha Ghanta, Timothy Winschel. Larissa Melnyk set up the 3D printing process. All aforementioned authors contributed to data presentation, manuscript writing and editing. Moses Oyewumi was also responsible for conceptualization of the research question, project supervision, administration, funding acquisition, experiment validation, manuscript review and editing. All authors read and approved the final manuscript.

Disclosure statement

The authors have no personal and/or financial conflict of interests to disclose.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

The work was supported by funding from Northeast Ohio Medical University Foundation.