Duan Jing, Fang Yongcong, Tian Yueming, Wang Ziyu, Yang Bin, Xiong Zhuo
Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, P. R. China.
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, P. R. China.
Adv Healthc Mater. 2025 Jun;14(16):e2501376. doi: 10.1002/adhm.202501376. Epub 2025 May 13.
Despite rapid advances in the field of bone tissue engineering, cranial bone defects of critical size remain difficult to repair due to the limited self-regeneration capacity of the bone. Developmental engineering with mesenchymal stem cells (MSCs) aggregates has shown promise for enhanced bone regeneration; however, these MSCs aggregates require extended in vitro osteogenic induction time and lack sufficient vascularization to enable rapid in situ osteogenesis. To address these issues, a novel strategy is introduced for the large-scale generation of prevascularized bone organoids with self-organized vascularization and enhanced osteogenic properties by combining MSCs, human umbilical vein endothelial cells, and osteogenic microparticles. The osteogenic differentiation effects across different microparticles were systematically evaluated and identified graphene oxide as the most effective, which primarily promoted osteogenesis through the focal adhesion and PI3K/Akt pathway. Further, the prevascularized bone organoid-laden hydrogels can be 3D printed into complex tissue constructs with high cell density and osteogenic capacity. In vivo experiments confirmed that this approach promoted rapid vascularized bone tissue formation, achieving effective in situ regeneration and repair of cranial bone defects. This innovative developmental engineering strategy provides a promising, scalable, and effective approach to bone regeneration, advancing developmental tissue engineering for therapeutic applications.
尽管骨组织工程领域取得了快速进展，但由于骨的自我再生能力有限，临界尺寸的颅骨缺损仍然难以修复。利用间充质干细胞（MSCs）聚集体进行发育工程已显示出增强骨再生的潜力；然而，这些MSCs聚集体需要延长体外成骨诱导时间，并且缺乏足够的血管化来实现快速原位成骨。为了解决这些问题，引入了一种新策略，通过将MSCs、人脐静脉内皮细胞和成骨微粒相结合，大规模生成具有自组织血管化和增强成骨特性的预血管化骨类器官。系统评估了不同微粒的成骨分化效果，确定氧化石墨烯是最有效的，其主要通过粘着斑和PI3K/Akt途径促进成骨。此外，负载预血管化骨类器官的水凝胶可以3D打印成具有高细胞密度和成骨能力的复杂组织构建体。体内实验证实，这种方法促进了快速血管化骨组织的形成，实现了颅骨缺损的有效原位再生和修复。这种创新的发育工程策略为骨再生提供了一种有前景、可扩展且有效的方法，推动了用于治疗应用的发育组织工程。
