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

Show Author's information Dongdong Wu1,2,§Hai Lei2,3,§Xian Xie1,2,§Liang Zhou1,2Peng Zheng1,2Yi Cao2,3( )Yan Zhang1,2( )
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
Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China
Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing 210093, China

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

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.

Keywords: biomaterials, hydrogel, peptide, self-assemble, photo click reaction

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Publication history
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Acknowledgements

Publication history

Received: 25 November 2021
Revised: 14 December 2021
Accepted: 19 December 2021
Published: 25 January 2022
Issue date: May 2022

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

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

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