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Nanofiber-induced hierarchically-porous magnesium phosphate bone cements accelerate bone regeneration by inhibiting Notch signaling.
Chen, Jingteng; Yu, Ling; Gao, Tian; Dong, Xiangyang; Li, Shiyu; Liu, Yinchu; Yang, Jian; Xia, Kezhou; Yu, Yaru; Li, Yingshuo; Wang, Sen; Fan, ZhengFu; Deng, Hongbing; Guo, Weichun.
Afiliación
  • Chen J; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Yu L; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Gao T; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
  • Dong X; Hubei Key Laboratory of Biomass Resource Chemistry and Environmental Biotechnology, Hubei International Scientific and Technological Cooperation Base of Sustainable Resource and Energy, School of Resource and Environmental Science, Wuhan University, Wuhan, 430079, China.
  • Li S; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Liu Y; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Yang J; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Xia K; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Yu Y; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Li Y; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Wang S; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • Fan Z; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
  • Deng H; Hubei Key Laboratory of Biomass Resource Chemistry and Environmental Biotechnology, Hubei International Scientific and Technological Cooperation Base of Sustainable Resource and Energy, School of Resource and Environmental Science, Wuhan University, Wuhan, 430079, China.
  • Guo W; Department of Spine Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Bioact Mater ; 37: 459-476, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38698920
ABSTRACT
Magnesium phosphate bone cements (MPC) have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability. However, their poor porosity and permeability limit osteogenic cell ingrowth and vascularization, which is critical for bone regeneration. In the current study, we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix (ECM)-mimicking electrospun silk fibroin (SF) nanofibers. The SF-embedded MPC (SM) exhibited a heterogeneous and hierarchical structure, which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth. Besides, the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide. Bone marrow stem cells (BMSCs) adhered excellently on SM, as illustrated by formation of more pseudopodia. CCK8 assay showed that SM promoted early proliferation of BMSCs. Our study also verified that SM increased the expression of OPN, RUNX2 and BMP2, suggesting enhanced osteogenic differentiation of BMSCs. We screened for osteogenesis-related pathways, including FAK signaing, Wnt signaling and Notch signaling, and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway, proved by the downregulation of NICD1, Hes1 and Hey2. In addition, using a bone defect model of rat calvaria, the study revealed that SM exhibited enhanced osteogenesis, bone ingrowth and vascularization compared with MPC alone. No adverse effect was found after implantation of SM in vivo. Overall, our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Bioact Mater Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Bioact Mater Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China