Dynamic GelMA/DNA Dual‐Network Hydrogels Promote Woven Bone Organoid Formation and Enhance Bone Regeneration,Advanced Materials

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Dynamic GelMA/DNA Dual‐Network Hydrogels Promote Woven Bone Organoid Formation and Enhance Bone Regeneration
Advanced Materials ( IF 27.4 ) Pub Date : 2025-03-24 , DOI: 10.1002/adma.202501254
Mengru Zhu _{1,

2} , Hao Zhang ₃ , Qirong Zhou ₃ , Shihao Sheng ₃ , Qianmin Gao _{1,

2} , Zhen Geng _{1,

2} , Xiao Chen ₃ , Yuxiao Lai ₄ , Yingying Jing _{1,

2} , Ke Xu _{1,

2} , Long Bai _{1,

2} , Guangchao Wang ₃ , Jianhua Wang ₃ , Yingying Jiang _{1,

2} , Jiacan Su _{1,

2,

3}

Affiliation

Bone organoids, in vitro models mimicking native bone structure and function, rely on 3D stem cell culture for self‐organization, differentiation, ECM secretion, and biomineralization, ultimately forming mineralized collagen hierarchies. However, their development is often limited by the lack of suitable matrices with optimal mechanical properties for sustained cell growth and differentiation. To address this, a dynamic DNA/Gelatin methacryloyl (GelMA) hydrogel (CGDE) is developed to recapitulate key biochemical and mechanical features of the bone ECM, providing a supportive microenvironment for bone organoid formation. This dual‐network hydrogel is engineered through hydrogen bonding between DNA and GelMA, combined with GelMA network crosslinking, resulting in appropriate mechanical strength and enhanced viscoelasticity. During a 21‐day 3D culture, the CGDE hydrogel facilitates cellular migration and self‐organization, promoting woven bone organoid (WBO) formation via intramembranous ossification. These WBOs exhibit spatiotemporal architectures supporting dynamic mineralization and tissue remodeling. In vivo studies demonstrate that CGDE‐derived WBOs exhibit self‐adaptive properties, enabling rapid osseointegration within 4 weeks. This work highlights the CGDE hydrogel as a robust and scalable platform for bone organoid development, offering new insights into bone biology and innovative strategies for bone tissue regeneration.

中文翻译：

动态 GelMA/DNA 双网络水凝胶促进编织骨类器官形成并增强骨再生

骨类器官是模拟天然骨骼结构和功能的体外模型，依靠 3D 干细胞培养进行自我组织、分化、ECM 分泌和生物矿化，最终形成矿化胶原蛋白层次结构。然而，由于缺乏具有持续细胞生长和分化的最佳机械特性的合适基质，它们的开发往往受到限制。为了解决这个问题，开发了一种动态 DNA/明胶甲基丙烯酰（GelMA）水凝胶（CGDE）来概括骨 ECM 的关键生化和机械特征，为骨类器官的形成提供支持性微环境。这种双网络水凝胶是通过 DNA 和 GelMA 之间的氢键结合 GelMA 网络交联设计的，从而产生适当的机械强度和增强的粘弹性。在 21 天的 3D 培养过程中，CGDE 水凝胶促进细胞迁移和自组织，通过膜内骨化促进编织骨类器官（WBO）的形成。这些 WBO 表现出支持动态矿化和组织重塑的时空结构。体内研究表明，CGDE 衍生的 WBO 表现出自适应特性，能够在 4 周内快速骨整合。这项工作突出了 CGDE 水凝胶作为骨类器官发育的强大且可扩展的平台，为骨生物学和骨组织再生的创新策略提供了新的见解。

更新日期：2025-03-24

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