LIU Zhirong,REN Xiaobin,YAO Qingqing, et al. Functionalized bioactive glass scaffold promotes orbital bone regeneration[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(9): 689-700.
Abstract：Objective: To enhance the osteogenic differentiation function of stem cells by doping metal ions into bioactive glass (BG) scaffolds and loading hypoxia-induced adipose-derived mesenchymal stem cell-derived exosomes (hExo) on the scaffold surface to enhance the scaffold’s angiogenic and anti-inflammatory properties,ultimately achieving orbital bone defect repair. Methods: Through ALP protein quantification and PCR analysis of osteogenesis-related gene expression, we compared the osteogenic effect of BMP2, IGF-1, hExo, Zn, and Sr on rADSCs to identify the most suitable osteogenic inducer and explore its optimal concentration. With hExo loaded onto BG/Zn scaffolds, their effects on angiogenesis, stem cell recruitment, and anti-inflammatory functions were investigated in vitro. Results: This study successfully fabricated Zn-doped and hExo-functionalized BG scaffolds using 3D printing technology. In vitro experimental results showed that Zn ions, compared with Sr ions, could serve as the most suitable osteogenic dopant, and the experiment of Zn ions incorporated into the BG scaffolds, the results demonstrated that a doping concentration of 10 mmol/L significantly promoted the expression of ALP protein and osteogenic-related genes OPN, RUNX2, ALP, OCN and BMP2 as well (P<0.01). Hypoxiainduced exosomes significantly promoted the expression of angiogenic factors HIF-1α, VEGF and chemokine SDF-1 (P<0.05), with the above pro-angiogenic function retained after hExo modification on the BG/Zn scaffold (P<0.05). Finally, BG, BG/Zn, and BG/Zn-hExo scaffolds were implanted into the orbital bone defect of New Zealand white rabbits for in vivo experiments, and the CT results demonstrated that the BG/Zn-hExo scaffold could significantly promote orbital bone regeneration. Conclusion: Zn ions and hExo, as safe and effective additives,can be utilized to functionalize BG scaffolds, which can enhance the scaffold’s osteogenic and angiogenic properties and optimize bone tissue engineering implant materials.
