Center of Dental Medicine, Oral Biotechnology & Bioengineering, University of Zurich, Plattenstrasse 11, 8032 Zurich, Switzerland.
Center for Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Int J Mol Sci. 2024 Mar 29;25(7):3826. doi: 10.3390/ijms25073826.
The functionalization of bone substitutes with exosomes appears to be a promising technique to enhance bone tissue formation. This study investigates the potential of exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) to improve bone healing and bone augmentation when incorporated into wide open-porous 3D-printed ceramic Gyroid scaffolds. We demonstrated the multipotent characteristics of BMSCs and characterized the extracted exosomes using nanoparticle tracking analysis and proteomic profiling. Through cell culture experimentation, we demonstrated that BMSC-derived exosomes possess the ability to attract cells and significantly facilitate their differentiation into the osteogenic lineage. Furthermore, we observed that scaffold architecture influences exosome release kinetics, with Gyroid scaffolds exhibiting slower release rates compared to Lattice scaffolds. Nevertheless, in vivo implantation did not show increased bone ingrowth in scaffolds loaded with exosomes, suggesting that the scaffold microarchitecture and material were already optimized for osteoconduction and bone augmentation. These findings highlight the lack of understanding about the optimal delivery of exosomes for osteoconduction and bone augmentation by advanced ceramic scaffolds.
外泌体对骨替代物的功能化似乎是一种很有前途的技术,可以增强骨组织的形成。本研究探讨了来源于骨髓间充质基质细胞(BMSC)的外泌体的潜力,当将其掺入到开放式大孔 3D 打印陶瓷 Gyroid 支架中时,可改善骨愈合和骨增量。我们证明了 BMSC 的多能特征,并使用纳米颗粒跟踪分析和蛋白质组学分析对提取的外泌体进行了表征。通过细胞培养实验,我们证明了 BMSC 衍生的外泌体具有吸引细胞的能力,并能显著促进其向成骨谱系分化。此外,我们观察到支架结构影响外泌体的释放动力学,与晶格支架相比,Gyroid 支架表现出较慢的释放速率。然而,体内植入并没有显示出负载外泌体的支架中骨向内生长的增加,这表明支架的微观结构和材料已经针对骨传导和骨增量进行了优化。这些发现强调了对于通过先进陶瓷支架进行骨传导和骨增量的外泌体最佳递送来理解的缺乏。