Li Wenshuai, Shen Qichen, Tong Tong, Tian Hongsen, Lian Xiaowei, Wang Haoli, Yang Ke, Dai Zhanqiu, Li Yijun, Chen Xianhua, Wang Qingqing, Yang Dan, Wang Feng, Hao Feng, Wang Linfeng
Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.
The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.
Bioact Mater. 2025 Apr 26;50:475-493. doi: 10.1016/j.bioactmat.2025.04.018. eCollection 2025 Aug.
Bone regeneration is a complex and coordinated physiological process, and the different stages of this process have corresponding microenvironments to support cell development and physiological activities. However, biological scaffolds that provide different three-dimensional environments during different stages of bone regeneration are lacking. In this study, we report a novel composite scaffold (NPE@DCBM) inspired by the stages of bone regeneration; this scaffold was composed of a fibrin hydrogel loaded with nanoplatelet vesicles (NPVs), designated as NPE, and decellularized cancellous bone matrix (DCBM) microparticles. Initially, the NPE rapidly established a temporary microenvironment conducive to cell migration and angiogenesis. Subsequently, the DCBM simulated the molecular structure of bone and promoted new bone formation. , the NPVs regulated lipid metabolism in bone marrow mesenchymal stem cells (BMSCs), reprogramed the fate of BMSCs by activating the PI3K/AKT and MAPK/ERK positive feedback pathways, and increased BMSC functions, including proliferation, migration and proangiogenic potential. , NPV@DCBM accelerated bone tissue regeneration and repair. Initially, the NPE rapidly induced angiogenesis between DCBM microparticles, and subsequently, BMSCs differentiated into osteoblasts with DCBM microparticles at their core. In summary, the design of this composite scaffold that sequentially mimics different bone regeneration microenvironments may provide a promising strategy for bone regeneration, with clinical translational potential.
骨再生是一个复杂且协调的生理过程，该过程的不同阶段具有相应的微环境来支持细胞发育和生理活动。然而，在骨再生的不同阶段提供不同三维环境的生物支架却很缺乏。在本研究中，我们报道了一种受骨再生阶段启发的新型复合支架（NPE@DCBM）；这种支架由负载纳米血小板囊泡（NPVs）的纤维蛋白水凝胶（称为NPE）和脱细胞松质骨基质（DCBM）微粒组成。最初，NPE迅速建立了一个有利于细胞迁移和血管生成的临时微环境。随后，DCBM模拟骨的分子结构并促进新骨形成。此外，NPVs调节骨髓间充质干细胞（BMSCs）中的脂质代谢，通过激活PI3K/AKT和MAPK/ERK正反馈途径重编程BMSCs的命运，并增强BMSCs的功能，包括增殖、迁移和促血管生成潜力。因此，NPV@DCBM加速了骨组织的再生和修复。最初，NPE迅速诱导DCBM微粒之间的血管生成，随后，BMSCs以DCBM微粒为核心分化为成骨细胞。总之，这种依次模拟不同骨再生微环境的复合支架设计可能为骨再生提供一种有前景的策略，具有临床转化潜力。
