Advanced Drug Delivery Laboratory, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH, USA.
School of Biomedical Sciences, Kent State University, Kent, OH, USA.
Pharm Dev Technol. 2024 Apr;29(4):339-352. doi: 10.1080/10837450.2024.2332459. Epub 2024 Mar 22.
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 degradation were not affected. NaOH-pretreated scaffolds showed the highest amount of GaAcAc loading when compared to other scaffolds ( < 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 ( < 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.
我们最近报道了一种新型镓化合物——乙酰丙酮镓(GaAcAc)通过抑制破骨细胞分化和功能,在对抗破骨细胞性骨吸收方面的潜力。在此,我们专注于负载 GaAcAc 的 3D 打印聚乳酸支架,并研究了支架用聚多巴胺(PDA)或氢氧化钠(NaOH)预处理的影响。我们观察到 PDA 或 NaOH 预处理后支架的亲水性显著增加,而生物相容性和降解不受影响。与其他支架相比,NaOH 预处理支架的 GaAcAc 负载量最高(<0.05)。与其他支架相比,负载 GaAcAc 的 NaOH 预处理支架显示出有效减少破骨细胞数量和大小的趋势,这一趋势得到了 NFAT2、c-Fos、TRAF6 和 TRAP 等关键破骨细胞分化标志物表达抑制的支持。所有负载 GaAcAc 的支架,无论表面预处理如何,都能有效抑制破骨细胞功能,这体现在减少牛皮质骨切片上的吸收陷窝数量上(<0.01)。根据支架类型抑制破骨细胞功能的效果排序为:无表面预处理的 GaAcAc 负载>NaOH 预处理的 GaAcAc 负载>PDA 预处理的 GaAcAc 负载。需要进一步研究来充分阐明表面预处理对负载 GaAcAc 的 3D 打印支架的疗效和安全性的影响。