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Self-sorting double network hydrogels with photo-definable biochemical cues as artificial synthetic extracellular matrix

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Abstract

In soft connective tissues, the extracellular matrix (ECM) provides spatiotemporally well-defined mechanical and chemical cues that regulate the functions of residing cells. However, it remains challenging to replicate these essential features in synthetic biomaterials. Here, we develop a self-sorting double network hydrogel (SDNH) with spatially well-defined bioactive ligands as synthetic ECM. Specifically, the SDNH is made of two peptides that can independently self-assemble into fibers of different microscopic features, mimicking the hierarchical protein assemblies in ECM. Each peptide contains a photo-reactive moiety for orthogonally patterning bioactive molecules (i.e., cyclic arginine-glycine-aspartate (cRGD) and osteogenic growth peptide (OGP)) using UV and visible light. As a proof-of-principle, we demonstrate the engineering of SDNH with spatially separated or colocalized cRGD and OGP molecules to control the response of encapsulated stem cells. Our study represents an important step towards defining the mechanical and biochemical cues of synthetic ECM using advanced chemical biology tools.

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Acknowledgements

This research is supported mainly by the National Natural Science Foundation of China (Nos. 22137003, 21977043, and 11804147).

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Author notes

  1. Dongdong Wu, Hai Lei, and Xian Xie contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Analytical Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China

    Dongdong Wu, Xian Xie, Liang Zhou, Peng Zheng & Yan Zhang

  2. Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210023, China

    Dongdong Wu, Hai Lei, Xian Xie, Liang Zhou, Peng Zheng, Yi Cao & Yan Zhang

  3. Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, 210093, China

    Hai Lei & Yi Cao

Authors
  1. Dongdong Wu
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  2. Hai Lei
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  3. Xian Xie
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  4. Liang Zhou
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  5. Peng Zheng
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  7. Yan Zhang
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Correspondence to Yi Cao or Yan Zhang.

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Self-sorting double network hydrogels with photo-definable biochemical cues as artificial synthetic extracellular matrix

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Wu, D., Lei, H., Xie, X. et al. Self-sorting double network hydrogels with photo-definable biochemical cues as artificial synthetic extracellular matrix. Nano Res. 15, 4294–4301 (2022). https://doi.org/10.1007/s12274-022-4089-9

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