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Oxygen tension regulating hydrogels for vascularization and osteogenesis via sequential activation of HIF-1α and ERK1/2 signaling pathways in bone regeneration.
Yin, Xianzhen; Wei, Yihao; Qin, Haotian; Zhao, Jin; Chen, Yixiao; Yao, Sen; Li, Nan; Xiong, Ao; Wang, Deli; Zhang, Peng; Liu, Peng; Zeng, Hui; Chen, Yingqi.
Afiliación
  • Yin X; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China; Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Aca
  • Wei Y; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.
  • Qin H; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.
  • Zhao J; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.
  • Chen Y; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.
  • Yao S; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.
  • Li N; Department of Stomatology, Shenzhen People's Hospital (Second Clinical Medical School of Jinan University, First Affiliated Hospital of Southern University of Science and Technology), Shenzhen 518020, China.
  • Xiong A; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.
  • Wang D; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.
  • Zhang P; Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
  • Liu P; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China. Electronic address: liupeng_polymer@126.com.
  • Zeng H; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China. Electronic address: zenghui@pkuszh.com.
  • Chen Y; Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China. Electronic address: yqchen0203@foxmail.com.
Biomater Adv ; 161: 213893, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38796955
ABSTRACT
Angiogenesis plays a crucial role in bone regeneration. Hypoxia is a driving force of angiogenesis at the initial stage of tissue repair. The hypoxic microenvironment could activate the hypoxia-inducible factor (HIF)-1α signaling pathway in cells, thereby enhancing the proliferation, migration and pro-angiogenic functions of stem cells. However, long-term chronic hypoxia could inhibit osteogenic differentiation and even lead to apoptosis. Therefore, shutdown of the HIF-1α signaling pathway and providing oxygen at later stage probably facilitate osteogenic differentiation and bone regeneration. Herein, an oxygen tension regulating hydrogel that sequentially activate and deactivate the HIF-1α signaling pathway were prepared in this study. Its effect and mechanism on stem cell differentiation were investigated both in vitro and in vivo. We proposed a gelatin-based hydrogel capable of sequentially delivering a hypoxic inducer (copper ions) and oxygen generator (calcium peroxide). The copper ions released from the hydrogels significantly enhanced cell viability and VEGF secretion of BMSCs via upregulating HIF-1α expression and facilitating its translocation into the nucleus. Additionally, calcium peroxide promoted alkaline phosphatase activity, osteopontin secretion, and calcium deposition through the activation of ERK1/2. Both Cu2+ and calcium peroxide demonstrated osteogenic promotion individually, while their synergistic effect within the hydrogels led to a superior osteogenic effect by potentially activating the HIF-1α and ERK1/2 signaling pathways.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Oxígeno / Regeneración Ósea / Neovascularización Fisiológica / Hidrogeles / Sistema de Señalización de MAP Quinasas / Subunidad alfa del Factor 1 Inducible por Hipoxia / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Biomater Adv Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Oxígeno / Regeneración Ósea / Neovascularización Fisiológica / Hidrogeles / Sistema de Señalización de MAP Quinasas / Subunidad alfa del Factor 1 Inducible por Hipoxia / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Biomater Adv Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos