Oxygen tension regulating hydrogels for vascularization and osteogenesis via sequential activation of HIF-1 α and ERK1/2 signaling pathways in bone regeneration

Yin, Xianzhen1; Wei, Yihao1; Qin, Haotian1; Zhao, Jin1; Chen, Yixiao1; Yao, Sen1; Li, Nan3; Xiong, Ao1; Wang, Deli1; Zhang, Peng2; Liu, Peng1; Zeng, Hui1; Chen, Yingqi1

2024-07-01

10.1016/j.bioadv.2024.213893

BIOMATERIALS ADVANCES   影响因子和分区

2772-9508

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)-1 alpha 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-1 alpha 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-1 alpha 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-1 alpha 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 Cu 2 + 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-1 alpha and ERK1/2 signaling pathways.

Copper ions Calcium peroxide HIF-1 alpha Angiogenesis Osteogenesis

SCI ; EI

英语

其他

National Natural Science Foundation of China["82202664","32000516","82172432"] ; Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research[ZDSYS20220606100602005] ; Basic and Applied Basic Research Foundation of Guangdong Province["2023A1515012764","2023A1515012754"] ; Shenzhen Science and Technology Project[JCYJ20190809165805604] ; Shenzhen High-level Hospital Construction Fund[SZXK023]

Materials Science

Materials Science, Biomaterials

WOS:001246334600001

ELSEVIER

Web of Science

1.Peking Univ, Shenzhen Hosp, Natl & Local Joint Engn Res Ctr Orthopaed Biomat, Dept Bone & Joint Surg, Shenzhen 518036, Peoples R China
2.Chinese Acad Sci, Ctr Translat Med Res & Dev, Shenzhen Inst Adv Technol, Shenzhen 518055, Peoples R China
3.Jinan Univ, Southern Univ Sci & Technol, Affiliated Hosp 1, Clin Med Coll 2,Shenzhen Peoples Hosp,Dept Stomato, Shenzhen 518020, Peoples R China

Yin, Xianzhen,Wei, Yihao,Qin, Haotian,et al. Oxygen tension regulating hydrogels for vascularization and osteogenesis via sequential activation of HIF-1 α and ERK1/2 signaling pathways in bone regeneration[J]. BIOMATERIALS ADVANCES,2024,161.

Yin, Xianzhen.,Wei, Yihao.,Qin, Haotian.,Zhao, Jin.,Chen, Yixiao.,...&Chen, Yingqi.(2024).Oxygen tension regulating hydrogels for vascularization and osteogenesis via sequential activation of HIF-1 α and ERK1/2 signaling pathways in bone regeneration.BIOMATERIALS ADVANCES,161.

Yin, Xianzhen,et al."Oxygen tension regulating hydrogels for vascularization and osteogenesis via sequential activation of HIF-1 α and ERK1/2 signaling pathways in bone regeneration".BIOMATERIALS ADVANCES 161(2024).