Exosomes, nanoscale extracellular vesicles crucial for intercellular communication, hold great promise as a therapeutic avenue in cell-free tissue regeneration. In this study, we identified and utilized exosomes to adorn anodized titanium scaffolds, inducing osteogenic differentiation in human dental pulp stem cells (hDPSCs). The osteogenesis of hDPSCs was stimulated by exosomes derived from hDPSCs that underwent various periods of osteogenic differentiation. After purification, these exosomes were loaded onto anodized titanium scaffolds. Notably, the scaffolds loaded with exosomes deriving from osteogenic differentiated hDPSCs demonstrated superior bone tissue regeneration compared to those loaded with exosomes deriving from hDPSCs within 10-week. RNA-sequencing analysis shed light on the underlying mechanism, revealing that the osteogenic exosomes carried specific cargo, which is due to upregulated miRNAs (Hsa-miR-29c-5p, Hsa-miR-378a-5p, Hsa-miR-10b-5p and Hsa-miR-9–3p) associated with osteogenesis. And down-regulated anti-osteogenic miRNA (Hsa-miR-31–3p, Hsa-miR-221–3p, Hsa-miR-183–5p and Hsa-miR-503–5p). In conclusion, the identification and utilization of exosomes derived from osteogenic differentiated stem cells offer a novel and promising strategy for achieving cell-free bone regeneration.

中文翻译：

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人牙髓干细胞衍生的外泌体装饰钛支架促进骨再生


外泌体是对细胞间通讯至关重要的纳米级细胞外囊泡，作为无细胞组织再生的治疗途径具有广阔的前景。在这项研究中，我们鉴定并利用外泌体装饰阳极氧化钛支架，诱导人牙髓干细胞（hDPSC）成骨分化。 hDPSCs 的成骨作用受到来自经历不同成骨分化时期的 hDPSCs 的外泌体的刺激。纯化后，这些外泌体被装载到阳极氧化钛支架上。值得注意的是，与负载来自 hDPSC 的外泌体的支架相比，负载来自成骨分化 hDPSC 的外泌体的支架在 10 周内表现出优异的骨组织再生能力。 RNA测序分析揭示了潜在的机制，揭示了成骨外泌体携带特定的货物，这是由于上调的miRNA（Hsa-miR-29c-5p、Hsa-miR-378a-5p、Hsa-miR-10b-5p）和 Hsa-miR-9–3p）与成骨相关。并下调抗成骨 miRNA（Hsa-miR-31–3p、Hsa-miR-221–3p、Hsa-miR-183–5p 和 Hsa-miR-503–5p）。总之，来自成骨分化干细胞的外泌体的鉴定和利用为实现无细胞骨再生提供了一种新颖且有前景的策略。