PDF(Pubmed)
Abstract：
Segmental bone defects, arising from factors such as trauma, tumor resection, and congenital malformations, present significant clinical challenges that often necessitate complex reconstruction strategies. Hydrogels loaded with multiple osteogenesis-promoting components have emerged as promising tools for bone defect repair. While the osteogenic potential of the Piezo1 agonist Yoda1 has been demonstrated previously, its hydrophobic nature poses challenges for effective loading onto hydrogel matrices.In this study, we address this challenge by employing Yoda1-pretreated bone marrow-derived mesenchymal stem cell (BMSCs) exosomes (Exo-Yoda1) alongside exosomes derived from BMSCs (Exo-MSC). Comparatively, Exo-Yoda1-treated BMSCs exhibited enhanced osteogenic capabilities compared to both control groups and Exo-MSC-treated counterparts. Notably, Exo-Yoda1-treated cells demonstrated similar functionality to Yoda1 itself. Transcriptome analysis revealed activation of osteogenesis-associated signaling pathways, indicating the potential transduction of Yoda1-mediated signals such as ErK, a finding validated in this study. Furthermore, we successfully integrated Exo-Yoda1 into gelatin methacryloyl (GelMA)/methacrylated sodium alginate (SAMA)/β-tricalcium phosphate (β-TCP) hydrogels. These Exo-Yoda1-loaded hydrogels demonstrated augmented osteogenesis in subcutaneous ectopic osteogenesis nude mice models and in rat skull bone defect model. In conclusion, our study introduces Exo-Yoda1-loaded GELMA/SAMA/β-TCP hydrogels as a promising approach to promoting osteogenesis. This innovative strategy holds significant promise for future widespread clinical applications in the realm of bone defect reconstruction.
摘要：
节段性骨缺损,由于创伤等因素，肿瘤切除,先天性畸形，提出了重大的临床挑战，通常需要复杂的重建策略。负载有多种骨生成促进成分的水凝胶已成为修复骨缺损的有希望的工具。虽然先前已经证明了Piezo1激动剂Yoda1的成骨潜力，其疏水性质对有效加载到水凝胶基质上提出了挑战。在这项研究中,我们通过使用Yoda1预处理的骨髓间充质干细胞(BMSCs)外泌体(Exo-Yoda1)和BMSCs(Exo-MSC)外泌体来应对这一挑战.相对而言,与对照组和Exo-MSC处理的对应物相比，Exo-Yoda1处理的BMSC表现出增强的成骨能力。值得注意的是,Exo-Yoda1处理的细胞表现出与Yoda1本身相似的功能。转录组分析显示成骨相关信号通路的激活，表明Yoda1介导的信号如ErK的潜在转导，这项研究验证了这一发现。此外，我们成功地将Exo-Yoda1整合到明胶甲基丙烯酰（GelMA）/甲基丙烯酸海藻酸钠（SAMA）/β-磷酸三钙（β-TCP）水凝胶中。这些加载Exo-Yoda1的水凝胶在皮下异位成骨裸鼠模型和大鼠颅骨骨缺损模型中显示出增强的成骨作用。总之,我们的研究引入了Exo-Yoda1负载的GELMA/SAMA/β-TCP水凝胶作为促进成骨的有希望的方法。这种创新策略对于骨缺损重建领域的未来广泛临床应用具有重要意义。
