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干细胞归巢仿生水凝胶通过成骨和成血管耦联促进骨质疏松性骨缺损的修复。

Stem cell-homing biomimetic hydrogel promotes the repair of osteoporotic bone defects through osteogenic and angiogenic coupling.

机构信息

Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, China.

Department of Orthopaedics, General Hospital of Central Theater Command (Wuhan General Hospital of Guangzhou Command, previously), Wuhan 430030, China.

出版信息

Sci Adv. 2024 Nov;10(44):eadq6700. doi: 10.1126/sciadv.adq6700. Epub 2024 Nov 1.

Abstract

Osteoporotic bone defects refer to the disruption of bone structural integrity in patients with osteoporosis and pose a substantial challenge to orthopedic surgeons. In this study, we developed a biomimetic hydrogel to improve the osteogenic microenvironment and promote stem cell homing. This hydrogel served as a container for S-nitrosoglutathione and Ca, promoting the release of bioactive nitric oxide (NO) from bone marrow mesenchymal stem cells (BMSCs) and human vascular endothelial cells and activating the NO/cyclic guanosine monophosphate signaling pathway. These changes promote osteogenic and angiogenic couplings. The hydrogel simultaneously recruited BMSCs by conjugating the stem cell homing peptide SKPPGTSS. Using a rat distal femoral defect model, it was demonstrated that this hydrogel can effectively increase the formation of bone tissue and new blood vessels and has immune-regulating functions. We envision that this hydrogel may be a minimally invasive yet highly effective strategy for expediting the healing of osteoporotic bone defects.

摘要

骨质疏松性骨缺损是指骨质疏松症患者骨结构完整性的破坏,给骨科医生带来了巨大的挑战。在这项研究中,我们开发了一种仿生水凝胶来改善成骨微环境并促进干细胞归巢。这种水凝胶作为 S-亚硝基谷胱甘肽和 Ca 的容器,促进了骨髓间充质干细胞(BMSCs)和人血管内皮细胞中生物活性一氧化氮(NO)的释放,并激活了 NO/环鸟苷酸信号通路。这些变化促进了成骨和血管生成的偶联。水凝胶通过连接干细胞归巢肽 SKPPGTSS 来募集 BMSCs。通过大鼠股骨远端缺损模型证实,该水凝胶可有效增加骨组织和新生血管的形成,且具有免疫调节功能。我们设想这种水凝胶可能是一种微创但非常有效的策略,可以加速骨质疏松性骨缺损的愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/354a/11529719/3385c4137367/sciadv.adq6700-f1.jpg

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