Liu Junzheng, Meng Zijie, Song Jidong, Yu Jiaming, Guo Qin, Zhang Jiahao, Wang Shuo, Wang Yulin, Qiu Zhennan, Zhang Xinyi, He Jiankang, Wang Wei
Comprehensive Orthopedics Department, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P. R. China.
State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an 710049, P. R. China.
ACS Appl Mater Interfaces. 2025 May 28;17(21):30559-30572. doi: 10.1021/acsami.5c03093. Epub 2025 May 16.
Yoda1 has been recognized as an effective pharmacological intervention for the treatment of critical bone defects. However, the local delivery strategy of Yoda1 is uncommon, and the underlying mechanism through which Yoda1 enhances osteogenesis has been poorly investigated. Here, we propose utilizing electrohydrodynamic (EHD)-printed microfibrous scaffolds as a drug carrier for loading Yoda1 through a polydopamine (PDA) coating, and the synthetic mechanisms for enhancing bone regeneration are explored. Yoda1 was successfully loaded on the surface of the EHD-printed microfibrous scaffolds with the assistance of PDA. The results of experiments demonstrated that the Yoda1-loaded microfibrous scaffold group exhibited a more than 2-fold increase in COL-I protein levels compared to the control group. Additionally, the expression levels of osteogenic indicators such as ALP, Runx2, and OCN genes were significantly increased by 2-4-fold compared to those in the control group. We revealed that Yoda1 can effectively activate the Piezo1-F-actin pathway, thereby facilitating YAP nucleation and promoting lysine histone acetylation. Consequently, this mechanism enhanced the functionality of YAP nucleation and upregulated the expression of COL-I. Moreover, when implanted , the Yoda1-loaded microfibrous scaffold group could promote macrophage M2 polarization, thereby enhancing bone regeneration at defect sites. It is believed that the localized release of Yoda1 via EHD-printed PCL scaffolds might represent a promising strategy for the clinically precise treatment of bone defects.
Yoda1已被公认为是治疗严重骨缺损的一种有效药物干预手段。然而，Yoda1的局部递送策略并不常见，且Yoda1促进成骨的潜在机制尚未得到充分研究。在此，我们提出利用电液动力（EHD）打印的微纤维支架作为药物载体，通过聚多巴胺（PDA）涂层来负载Yoda1，并探索其增强骨再生的合成机制。在PDA的辅助下，Yoda1成功负载到EHD打印的微纤维支架表面。实验结果表明，与对照组相比，负载Yoda1的微纤维支架组的COL-I蛋白水平增加了两倍多。此外，与对照组相比，成骨指标如ALP、Runx2和OCN基因的表达水平显著提高了2至4倍。我们发现Yoda1可以有效激活Piezo1-F-肌动蛋白途径，从而促进YAP成核并促进赖氨酸组蛋白乙酰化。因此，这一机制增强了YAP成核的功能并上调了COL-I的表达。此外，植入后，负载Yoda1的微纤维支架组可促进巨噬细胞M2极化，从而增强缺损部位的骨再生。据信，通过EHD打印的聚己内酯支架实现Yoda1的局部释放可能是临床上精确治疗骨缺损的一种有前景的策略。
