Kadoya Koichi, Hara Emilio Satoshi, Okada Masahiro, Jiao Yu Yang, Nakano Takayoshi, Sasaki Akira, Matsumoto Takuya
Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Department of Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Regen Biomater. 2022 Nov 2;10:rbac088. doi: 10.1093/rb/rbac088. eCollection 2023.
The extracellular matrix of trabecular bone has a large surface exposed to the bone marrow and plays important roles such as hematopoietic stem cell niche formation and maintenance. reproduction of trabecular bone microenvironment would be valuable not only for developing a functional scaffold for bone marrow tissue engineering but also for understanding its biological functions. Herein, we analyzed and reproduced the initial stages of trabecular bone formation in mouse femur epiphysis. We identified that the trabecular bone formation progressed through the following steps: (i) partial rupture of hypertrophic chondrocytes; (ii) calcospherite formation on cell membrane nano fragments (CNFs) derived from the ruptured cells; and (iii) calcospherite growth and fusion to form the initial three-dimensional (3D) structure of trabecular bones. For reproducing the initial trabecular bone formation , we collected CNFs from cultured cells and used as nucleation sites for biomimetic calcospherite formation. Strikingly, almost the same 3D structure of the initial trabecular bone could be obtained by using additional CNFs as a binder to fuse biomimetic calcospherites.
松质骨的细胞外基质有很大一部分表面暴露于骨髓，并且发挥着重要作用，如造血干细胞龛的形成与维持。松质骨微环境的重现不仅对于开发用于骨髓组织工程的功能性支架具有重要价值，而且对于理解其生物学功能也具有重要意义。在此，我们分析并重现了小鼠股骨骨骺处松质骨形成的初始阶段。我们确定松质骨形成过程经历以下步骤：（i）肥大软骨细胞的部分破裂；（ii）在源自破裂细胞的细胞膜纳米碎片（CNFs）上形成钙球；以及（iii）钙球生长并融合以形成松质骨的初始三维（3D）结构。为了重现初始松质骨形成过程，我们从培养细胞中收集CNFs，并将其用作仿生钙球形成的成核位点。令人惊讶的是，通过使用额外的CNFs作为粘合剂来融合仿生钙球，几乎可以获得与初始松质骨相同的3D结构。
