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Crosstalk between PC12 cells and endothelial cells in an artificial neurovascular niche constructed by a dual-functionalized self-assembling peptide nanofiber hydrogel

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Abstract

The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration. Recently, using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention. Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials. In this study, we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ (RGI) and KLTWQELYQLKYKGI (KLT) to construct an artificial neurovascular microenvironment. The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma (PC12) cells and tube-like structures formation of human umbilical vein endothelial cells (HUVECs) in vitro, and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model. Using indirect co-culture models, we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs. When the two cells types were directly co-cultured on the dual-functionalized peptide hydrogel, the efficiency of cell-cell communication was enhanced, which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology, and HUVECs tube-like structure formation. In summary, the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.

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Acknowledgements

We acknowledge the financial support from the National Key R&D Program of China (Nos. 2020YFC1107600 and 2018YFB0704304), the National Natural Science Foundation of China (Nos. 31771056 and 31771052), and Shandong Province Key R&D Program of China (No. 2019JZZY011106).

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    Authors and Affiliations

    1. State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China

      Zhe Zhang, Shuhui Yang, Weilong Ye, Xiaodan Sun, Lingyun Zhao & Xiumei Wang

    2. Department of Neurosurgery, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 100084, China

      Yi Chai, Xiaohan Gao, Tuoyu Chen & Yuqi Zhang

    3. Institute of Smart Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China

      Xiangdong Kong & Jiaju Lu

    4. Department of orthopedics, Dongzhimen hospital, Beijing University of Chinese medicine, Beijing, 100700, China

      He Zhao

    5. Department of Neurosurgery, The First Hospital of Hebei Medical University, Shijiazhuang, 050000, China

      Wei Liu

    6. Department of Obstetrics and Gynecology, Beijing Tsinghua Changgung Hospital, Beijing, 102218, China

      Zihui Yang

    7. Department of Chemistry, Tsinghua University, Beijing, 100084, China

      Chenlong Wang

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    1. Zhe Zhang
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    Crosstalk between PC12 cells and endothelial cells in an artificial neurovascular niche constructed by a dual-functionalized self-assembling peptide nanofiber hydrogel

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    Zhang, Z., Chai, Y., Zhao, H. et al. Crosstalk between PC12 cells and endothelial cells in an artificial neurovascular niche constructed by a dual-functionalized self-assembling peptide nanofiber hydrogel. Nano Res. 15, 1433–1445 (2022). https://doi.org/10.1007/s12274-021-3684-5

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