Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Sports Medicine, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.
Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
Biomaterials. 2022 Sep;288:121741. doi: 10.1016/j.biomaterials.2022.121741. Epub 2022 Aug 19.
Large bone defects that cannot form a callus tissue are often faced with long-time recovery. Developmental engineering-based strategies with mesenchymal stem cell (MSC) aggregates have shown enhanced potential for bone regeneration. However, MSC aggregates are different from the physiological callus tissues, which limited the further endogenous osteogenesis. This study aims to achieve engineering of osteo-callus organoids for rapid bone regeneration in cooperation with bone marrow-derived stem cell (BMSC)-loaded hydrogel microspheres (MSs) by digital light-processing (DLP) printing technology and stepwise-induction. The printed MSC-loaded MSs aggregated into osteo-callus organoids after chondrogenic induction and showed much higher chondrogenic efficiency than that of traditional MSC pellets. Moreover, the osteo-callus organoids exhibited stage-specific gene expression pattern that recapitulated endochondral ossification process, as well as a synchronized state of cell proliferation and differentiation, which highly resembled the diverse cell compositions and behaviors of developmentally endochondral ossification. Lastly, the osteo-callus organoids efficiently led to rapid bone regeneration within only 4 weeks in a large bone defect in rabbits which need 2-3 months in previous tissue engineering studies. The findings suggested that in vitro engineering of osteo-callus organoids with developmentally osteogenic properties is a promising strategy for rapid bone defect regeneration and recovery.
对于无法形成愈伤组织的大骨缺损，往往需要长时间的恢复。基于间充质干细胞（MSC）聚集的发育工程策略已显示出增强骨再生的潜力。然而，MSC 聚集物与生理愈伤组织不同，这限制了进一步的内源性成骨作用。本研究旨在通过数字光处理（DLP）打印技术和逐步诱导，与骨髓来源的干细胞（BMSC）负载的水凝胶微球（MS）合作，实现工程化的类成骨组织，以快速促进骨再生。打印的负载 MSC 的 MS 在软骨诱导后聚集形成类成骨组织，其软骨生成效率明显高于传统的 MSC 微球。此外，类成骨组织表现出特定于阶段的基因表达模式，再现了软骨内骨化过程，以及细胞增殖和分化的同步状态，这非常类似于发育性软骨内骨化的多种细胞组成和行为。最后，类成骨组织在兔的大骨缺损中仅在 4 周内即可有效促进快速骨再生，而在之前的组织工程研究中需要 2-3 个月。这些发现表明，具有发育性成骨特性的体外工程化类成骨组织是一种很有前途的快速骨缺损再生和恢复策略。
