<br>3D打印骨再生支架通过血管化调节骨代谢稳态，治疗骨质疏松性骨缺损,Biomaterials

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3D打印骨再生支架通过血管化调节骨代谢稳态，治疗骨质疏松性骨缺损
Biomaterials ( IF 12.8 ) Pub Date : 2024-07-06 , DOI: 10.1016/j.biomaterials.2024.122699
Caiping Yan ₁ , Pengrui Zhang ₂ , Qiwei Qin ₂ , Ke Jiang ₂ , Yue Luo ₂ , Chao Xiang ₃ , Jiangtao He ₂ , Lu Chen ₂ , Dianming Jiang ₄ , Wenguo Cui ₅ , Yuling Li ₆

Affiliation

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Orthopedic Laboratory of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, PR China; Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, PR China.
Department of Orthopedics, Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, No. 1 The South of Maoyuan Road, Nanchong, Sichuan, 637000, PR China.
Department of Orthopedics, Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, No. 1 The South of Maoyuan Road, Nanchong, Sichuan, 637000, PR China; Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, PR China.
Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, PR China.
Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China.
Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Orthopedic Laboratory of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, PR China; Department of Orthopedics, Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, No. 1 The South of Maoyuan Road, Nanchong, Sichuan, 637000, PR China.

由于骨骼血管系统的退化和骨质疏松微环境中局部骨代谢的破坏，骨质疏松性骨缺损的治疗提出了挑战。然而，通过增强血管化来调节被破坏的局部骨代谢失衡是可行的，这一理论被称为“血管化-骨代谢平衡”。本研究开发了一种用 EPLQLKM 和 SVVYGLR 肽 (PCL-SE) 修饰的 3D 打印聚己内酯 (PCL) 支架。 EPLQLKM肽吸引骨髓间充质干细胞（BMSCs），而SVVYGLR肽增强内皮祖细胞（EPCs）血管分化，从而通过EPCs的旁分泌作用调节骨代谢并促进骨再生。进一步的机制研究表明，PCL-SE促进EPCs的血管化，激活BMSCs中的Notch信号通路，导致成骨相关基因的上调和破骨细胞相关基因的下调，从而恢复骨代谢平衡。此外，PCL-SE 促进 EPC 分化为“H”型血管，并招募 BMSC 来协同增强成骨作用，从而导致骨质疏松 SD 大鼠股骨髁骨缺损的正常微血管和骨组织再生。这项研究表明，PCL-SE 支持原位血管化，重塑骨代谢平移平衡，并为骨质疏松性骨缺损提供有前景的治疗方案。

"点击查看英文标题和摘要"

3D-printed bone regeneration scaffolds modulate bone metabolic homeostasis through vascularization for osteoporotic bone defects

The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.

更新日期：2024-07-06

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