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一种受骨折愈合细胞相互作用启发的用于骨组织工程的3D共培养系统。

A 3D Co-Culture System Inspired by Fracture Healing Cell Interactions for Bone Tissue Engineering.

作者信息

Wu Jicenyuan, Wang Yuxuan, Wang Liang, Xie Wenjia, Wan Qianbing, Wang Jian, Chen Junyu, Pei Xibo, Zhu Zhou

机构信息

State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.

出版信息

Adv Healthc Mater. 2025 Jun;14(16):e2500534. doi: 10.1002/adhm.202500534. Epub 2025 May 20.


DOI:10.1002/adhm.202500534
PMID:40394923
Abstract

Peri-bone fibroblasts play a crucial role in regulating bone regeneration during early fracture healing. Inspired by the synergy between osteoblasts and fibroblasts at fracture sites, a biomimetic three-dimensional (3D) indirect co-culture system is developed, comprising a 3D scaffold and co-cultured cells. To mimic cellular interactions in the fracture healing zone, the scaffold features an inner-outer ring structure with communication channels that support indirect cell co-culture. This setup provides fibroblasts and osteoblasts with a 3D culture environment resembling the in vivo extracellular matrix, enhancing intercellular signaling while minimizing risks of direct contact. Mechanically tunable bioinks are formulated by incorporating hyaluronic acid methacrylate (HAMA) hydrogel into gelatin methacryloyl (GelMA) hydrogel to construct the scaffold. The optimal co-culture ratio is established in vitro, where fibroblasts are found to regulate the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via zinc ion transport mechanisms. In vivo validations are conducted, including ectopic bone formation in nude mice and bone regeneration in rat cranial defect and tooth extraction socket models. This 3D indirect co-culture system enhances osteogenesis by promoting functional fibroblast-osteoblast interactions, offering a novel platform for co-culture studies and a promising strategy for clinical bone regeneration applications.

摘要

骨周成纤维细胞在骨折早期愈合过程中调节骨再生方面发挥着关键作用。受骨折部位成骨细胞与成纤维细胞之间协同作用的启发,开发了一种仿生三维(3D)间接共培养系统,该系统由3D支架和共培养细胞组成。为了模拟骨折愈合区域的细胞相互作用,该支架具有内外环结构以及支持间接细胞共培养的连通通道。这种设置为成纤维细胞和成骨细胞提供了类似于体内细胞外基质的3D培养环境,增强了细胞间信号传导,同时将直接接触的风险降至最低。通过将甲基丙烯酸透明质酸(HAMA)水凝胶掺入甲基丙烯酰明胶(GelMA)水凝胶中来配制机械可调生物墨水,以构建支架。在体外确定了最佳共培养比例,发现成纤维细胞通过锌离子转运机制调节骨髓间充质干细胞(BMSC)的成骨分化。进行了体内验证,包括裸鼠异位骨形成以及大鼠颅骨缺损和拔牙窝模型中的骨再生。这种3D间接共培养系统通过促进功能性成纤维细胞 - 成骨细胞相互作用增强了骨生成,为共培养研究提供了一个新平台,并为临床骨再生应用提供了一种有前景的策略。

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