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Bioactive polypeptide hydrogels modified with RGD and N-cadherin mimetic peptide promote chondrogenic differentiation of bone marrow mesenchymal stem cells

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Abstract

Cell-material and cell-cell interactions represent two crucial aspects of the regulation of cell behavior. In the present study, poly (L-glutamic acid) (PLG) hydrogels were prepared by catalyst-free click crosslinking via a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction between azido-grafted PLG (PLG-N3) and azadibenzocyclooctyne-grafted PLG (PLG-ADIBO). The bioactive peptides c(RGDfK) and N-cadherin mimetic peptide (N-Cad) were both conjugated to the PLG hydrogel (denoted PLG+RGD/N-Cad) in order to regulate cell-material and cell-cell interactions. Gelation time and storage modulus of the hydrogels were tunable through variations in the concentration of polypeptide precursors. The hydrogels degraded gradually in the presence of proteinases. The viability of bone marrow mesenchymal stem cells (BMSCs) was maintained when cultured with extracts of the hydrogels or encapsulated within the hydrogels. Degradation was observed within 10 weeks following the subcutaneous injection of hydrogel solution in rats, displaying excellent histocompatibility in vivo. The introduction of RGD into the PLG hydrogel promoted the adhesion of BMSCs onto the hydrogels. Moreover, when encapsulated within the PLG+RGD/N-Cad hydrogel, BMSCs secreted cartilage-specific matrix, in addition to chondrogenic gene and protein expression being significantly enhanced in comparison with BMSCs encapsulated in hydrogels without N-Cad modification. These findings suggest that these biodegradable, bioactive polypeptide hydrogels have great potential for use in 3D cell culture and in cartilage tissue engineering.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (51973218, 51622307, 21574127, 51520105004) and the Youth Innovation Promotion Association, Chinese Academy of Sciences.

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Authors and Affiliations

  1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Yan Rong, Zhen Zhang, Chaoliang He & Xuesi Chen

  2. University of Chinese Academy of Sciences, Beijing, 100039, China

    Yan Rong

  3. University of Science and Technology of China, Hefei, 230026, China

    Zhen Zhang, Chaoliang He & Xuesi Chen

Authors
  1. Yan Rong
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  2. Zhen Zhang
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  3. Chaoliang He
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  4. Xuesi Chen
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Correspondence to Chaoliang He.

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Bioactive polypeptide hydrogels modified with RGD and N-cadherin mimetic peptide promote chondrogenic differentiation of bone marrow mesenchymal stem cells

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Rong, Y., Zhang, Z., He, C. et al. Bioactive polypeptide hydrogels modified with RGD and N-cadherin mimetic peptide promote chondrogenic differentiation of bone marrow mesenchymal stem cells. Sci. China Chem. 63, 1100–1111 (2020). https://doi.org/10.1007/s11426-020-9772-0

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  • DOI: https://doi.org/10.1007/s11426-020-9772-0

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