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骨细胞中的 SB216763 激活经典 Wnt 信号构建多功能 4D 智能成骨模块。

The Osteocyte with SB216763-Activated Canonical Wnt Signaling Constructs a Multifunctional 4D Intelligent Osteogenic Module.

机构信息

Laboratory of Skeletal Development and Regeneration, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.

出版信息

Biomolecules. 2024 Mar 15;14(3):354. doi: 10.3390/biom14030354.

DOI:10.3390/biom14030354
PMID:38540772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10968156/
Abstract

The enhancement of bioactivity in materials has become an important focus within the field of bone tissue engineering. Four-dimensional intelligent osteogenic module, an innovative fusion of 3D printing with the time axis, shows immense potential in augmenting the bioactivity of these materials, thereby facilitating autologous bone regeneration efficiently. This study focuses on novel bone repair materials, particularly bioactive scaffolds with a developmental osteogenic microenvironment prepared through 3D bioprinting technology. This research mainly creates a developmental osteogenic microenvironment named "DOME". This is primed by the application of a small amount of the small molecule drug SB216763, which activates canonical Wnt signaling in osteocytes, promoting osteogenesis and mineralization nodule formation in bone marrow stromal cells and inhibiting the formation of adipocytes. Moreover, DOME enhances endothelial cell migration and angiogenesis, which is integral to bone repair. More importantly, the DOME-PCI3D system, a 4D intelligent osteogenic module constructed through 3D bioprinting, stably supports cell growth (91.2% survival rate after 7 days) and significantly increases the expression of osteogenic transcription factors in bone marrow stromal cells and induces osteogenic differentiation and mineralization for 28 days. This study presents a novel approach for bone repair, employing 3D bioprinting to create a multifunctional 4D intelligent osteogenic module. This innovative method not only resolves challenges related to shape-matching and biological activity but also demonstrates the vast potential for applications in bone repair.

摘要

材料生物活性的增强已成为骨组织工程领域的一个重要焦点。四维度智能成骨模块,是 3D 打印与时间轴的创新性融合,在增强这些材料的生物活性方面显示出巨大的潜力,从而有效地促进自体骨再生。本研究专注于新型骨修复材料,特别是通过 3D 生物打印技术制备的具有发育性成骨微环境的生物活性支架。本研究主要创建了一个名为“DOME”的发育性成骨微环境。这是通过应用少量小分子药物 SB216763 实现的,该药物激活成骨细胞中的经典 Wnt 信号通路,促进骨髓基质细胞中的成骨和矿化结节形成,并抑制脂肪细胞的形成。此外,DOME 增强内皮细胞迁移和血管生成,这对骨修复至关重要。更重要的是,通过 3D 生物打印构建的四维度智能成骨模块 DOME-PCI3D 系统稳定支持细胞生长(7 天后存活率为 91.2%),并显著增加骨髓基质细胞中成骨转录因子的表达,诱导成骨分化和矿化 28 天。本研究提出了一种新的骨修复方法,采用 3D 生物打印技术创建多功能的四维度智能成骨模块。这种创新方法不仅解决了形状匹配和生物活性相关的挑战,还展示了在骨修复应用中的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/5914bbf929d3/biomolecules-14-00354-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/eb40baf85f88/biomolecules-14-00354-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/1cd1a5e94ead/biomolecules-14-00354-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/4c0ac88557bf/biomolecules-14-00354-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/72f503afe399/biomolecules-14-00354-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/7e0862290e8b/biomolecules-14-00354-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/161434ba6f9e/biomolecules-14-00354-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/5914bbf929d3/biomolecules-14-00354-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/eb40baf85f88/biomolecules-14-00354-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/1cd1a5e94ead/biomolecules-14-00354-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/4c0ac88557bf/biomolecules-14-00354-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/72f503afe399/biomolecules-14-00354-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/7e0862290e8b/biomolecules-14-00354-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/161434ba6f9e/biomolecules-14-00354-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/10968156/5914bbf929d3/biomolecules-14-00354-g007.jpg

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