Injectable HAMA-CPC hydrogels loaded with high-yield 3D bioprinted adipose-derived stem cell small extracellular vesicles for increased bone repair

作者：Wenbin Xu, Wenling Gao, Yi Zhang, Gang Hou, Wenhui Zhang, Jintao Deng, Kun Wang, Yichun Xu, Boxun Liu, Tao Xu, Chang Liu, Tangzhao Liang · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03596-4 · 被引用次数：11 · 研究领域：Extracellular vesicles in disease、Immune cells in cancer、Connective tissue disorders research

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.