Xu Wenbin, Gao Wenling, Zhang Yi, Hou Gang, Zhang Wenhui, Deng Jintao, Wang Kun, Xu Yichun, Liu Boxun, Xu Tao, Liu Chang, Liang Tangzhao
Department of Orthopaedic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Department of Orthodontics, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510060, China.
J Nanobiotechnology. 2025 Jul 21;23(1):531. doi: 10.1186/s12951-025-03596-4.
In the field of bone tissue engineering, the development of effective strategies for bone defect repair remains a major challenge. Herein, we report a novel approach involving the integration of high-yield 3D bioprinted adipose-derived stem cell small extracellular vesicles (3D-sEVs) into an injectable HAMA-CPC hydrogel (HAMA-CPC@3D-sEVs). In vitro, HAMA-CPC@3D-sEVs significantly promoted the proliferation, migration, and osteogenic differentiation of bone marrow stromal cells (BMSCs) and promoted angiogenesis in human umbilical vein endothelial cells (HUVECs). In vivo, in a rat tibial defect model, this treatment strongly promoted bone regeneration, increasing the bone volume fraction (BV/TV), bone volume (BV), and trabecular thickness (Tb.Th) at 4 weeks post-surgery. Mechanistically, proteomic analysis revealed that NAMPT in 3D-sEVs upregulated S1PR1 in HUVECs, leading to increased VEGF expression and angiogenesis. These findings suggest that 3D-sEVs-functionalized HAMA-CPC hydrogels have good potential for bone defect repair.
在骨组织工程领域，开发有效的骨缺损修复策略仍然是一项重大挑战。在此，我们报告了一种新方法，即将高产率3D生物打印脂肪来源干细胞小细胞外囊泡（3D-sEVs）整合到可注射的HAMA-CPC水凝胶（HAMA-CPC@3D-sEVs）中。在体外，HAMA-CPC@3D-sEVs显著促进骨髓基质细胞（BMSCs）的增殖、迁移和成骨分化，并促进人脐静脉内皮细胞（HUVECs）的血管生成。在体内，在大鼠胫骨缺损模型中，这种治疗方法强烈促进骨再生，在术后4周时增加了骨体积分数（BV/TV）、骨体积（BV）和小梁厚度（Tb.Th）。从机制上讲，蛋白质组学分析表明，3D-sEVs中的NAMPT上调了HUVECs中的S1PR1，导致VEGF表达增加和血管生成。这些发现表明，3D-sEVs功能化的HAMA-CPC水凝胶在骨缺损修复方面具有良好的潜力。
