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仿生海洋海绵衍生的骨针微粒介导的生物矿化及YAP/TAZ通路促进体内骨再生

Biomimetic Marine-Sponge-Derived Spicule-Microparticle-Mediated Biomineralization and YAP/TAZ Pathway for Bone Regeneration In Vivo.

作者信息

Choi Sumi, Kim Jung Hun, Kang Tae Hoon, An Young-Hyeon, Lee Sang Jin, Hwang Nathaniel S, Kim Su-Hwan

机构信息

Department of Chemical Engineering (BK21 FOUR), Dong-A University, Busan 49315, Republic of Korea.

School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea.

出版信息

Biomater Res. 2024 Jul 25;28:0056. doi: 10.34133/bmr.0056. eCollection 2024.

DOI:10.34133/bmr.0056
PMID:39055902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11268990/
Abstract

Marine-sponge-derived spicule microparticles (SPMs) possess unique structural and compositional features suitable for bone tissue engineering. However, significant challenges remain in establishing their osteogenic mechanism and practical application in animal models. This study explores the biomimetic potential of SPM in orchestrating biomineralization behavior and modulating the Yes-associated protein 1/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) pathway both in vitro and in vivo. Characterization of SPM revealed a structure comprising amorphous silica oxide mixed with collagen and trace amounts of calcium and phosphate ions, which have the potential to facilitate biomineralization. Structural analysis indicated dynamic biomineralization from SPM to hydroxyapatite, contributing to both in vitro and in vivo osteoconductions. In vitro assessment demonstrated dose-dependent increases in osteogenic gene expression and bone morphogenetic protein-2 protein in response to SPM. In addition, focal adhesion mediated by silica diatoms induced cell spreading on the surface of SPM, leading to cell alignment in the direction of SPM. Mechanical signals from SPM subsequently increased the expression of YAP/TAZ, thereby inducing osteogenic mechanotransduction. The osteogenic activity of SPM-reinforced injectable hydrogel was evaluated in a mouse calvaria defect model, demonstrating rapid vascularized bone regeneration. These findings suggest that biomimetic SPM holds significant promise for regenerating bone tissue.

摘要

海洋海绵来源的骨针微粒（SPM）具有适合骨组织工程的独特结构和组成特征。然而，在确定其成骨机制以及在动物模型中的实际应用方面，仍存在重大挑战。本研究探讨了SPM在体外和体内协调生物矿化行为以及调节Yes相关蛋白1/含PDZ结合基序的转录共激活因子（YAP/TAZ）信号通路的仿生潜力。对SPM的表征显示，其结构由无定形氧化硅与胶原蛋白以及痕量的钙和磷酸根离子混合而成，具有促进生物矿化的潜力。结构分析表明，从SPM到羟基磷灰石存在动态生物矿化，这有助于体外和体内的骨传导。体外评估表明，SPM可使成骨基因表达和骨形态发生蛋白-2蛋白呈剂量依赖性增加。此外，硅质硅藻介导的粘着斑诱导细胞在SPM表面铺展，导致细胞沿SPM方向排列。来自SPM的机械信号随后增加了YAP/TAZ的表达，从而诱导成骨机械转导。在小鼠颅骨缺损模型中评估了SPM增强的可注射水凝胶的成骨活性，结果表明其能实现快速的血管化骨再生。这些发现表明，仿生SPM在骨组织再生方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/b40ac9aba708/bmr.0056.fig.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/8e7b4e910286/bmr.0056.fig.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/22344e265c98/bmr.0056.fig.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/b40ac9aba708/bmr.0056.fig.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/8e7b4e910286/bmr.0056.fig.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/4024ef5a7329/bmr.0056.fig.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/1512bd95aef2/bmr.0056.fig.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/01e1b7bf7418/bmr.0056.fig.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/22344e265c98/bmr.0056.fig.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3c4/11268990/b40ac9aba708/bmr.0056.fig.009.jpg

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