SCIENCE CHINA Chemistry, Volume 63 , Issue 8 : 1100-1111(2020) https://doi.org/10.1007/s11426-020-9772-0

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

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  • ReceivedApr 7, 2020
  • AcceptedMay 9, 2020
  • PublishedJun 8, 2020



the National Natural Science Foundation of China(51973218,51622307,21574127,51520105004)

the Youth Innovation Promotion Association

Chinese Academy of Sciences.


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.

Interest statement

The authors declare no conflict of interest.

Supplementary data

Supporting Information

The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Figure 1

    (a) Schematic diagram of the formation of click-crosslinked polypeptide hydrogels from PLG-N3 and PLG-ADIBO for use as a cell delivery vehicle. (b) Bioactive c(RGDfK) and N-cadherin mimetic peptides introduced into the PLG backbone to construct bioactive polypeptide hydrogels (color online).

  • Scheme 1

    Routes of synthesis of PLG-ADIBO, PLG-N3 and PLG-N3/RGD/N-Cad (color online).

  • Figure 2

    1H NMR spectra of PLG (a), PLG-ADIBO (b), PLG-N3/RGD/N-Cad (c) in D2O (color online).

  • Figure 3

    (a) Photographs of the sol-gel transition of 3% (w/v) PLG. (b) Gelation time of different concentrations of PLG hydrogels at 37 °C. (c) SEM image of lyophilized 3% (w/v) PLG hydrogels. Scale bar: 100 μm. (d) Storage modulus (G′) and loss modulus (G″) of PLG hydrogels with different concentrations as a function of time. (e) In vitro degradation profiles for the 3% (w/v) hydrogels incubated in 0.01 M PBS (pH 7.4) containing 5 U/mL proteinase K, 5 U/mL elastase, and PBS without any proteinase as control, respectively (n=3) (color online).

  • Figure 4

    (a) Viability of BMSCs after exposure to the supernatant of 3% (w/v) PLG hydrogels for 24 h. PEI 25K was used as a positive control (n=3). (b, c) Confocal images of BMSCs after encapsulation in 3% (w/v) PLG hydrogels for 48 h: (b) cells were stained with Alexa Fluor 488-Phalloidin (F-actin, green) and DAPI (cell nuclei, blue). Scale bar: 50 μm; (c) cells were stained with calcein-AM and PI. Scale bar: 100 μm. (d) Live-dead cell staining of BMSCs in 3% (w/v) PLG hydrogels after incubation for 7 or 14 days. Cells were stained with calcein-AM (green, live) and PI (red, dead). Scale bar: 100 μm (color online).

  • Figure 5

    (a) In vivo implantation of 3% (w/v) PLG hydrogels after various time intervals. (b) H&E staining images of tissues surrounding the injection sites at different time periods. Scale bar: 100 μm (color online).

  • Figure 6

    (a) Proliferation of chondrocytes encapsulated in 3% (w/v) PLG hydrogels as a function of time. (b) Proliferation of BMSCs within the three types of hydrogel: 3% (w/v) PLG hydrogels, 3% (w/v) PLG+RGD/Scram hydrogels, 3% (w/v) PLG+RGD/N-Cad hydrogels (n=3), (**p<0.01, ***p<0.001) (color online).

  • Figure 7

    Chondrogenic differentiation of BMSCs in response to N-Cad-modified 3D hydrogels. (a) Quantification of GAG in hydrogels containing BMSCs after induction of chondrogenesis in culture for 3 weeks (normalized to DNA content). (b, c) Quantitative RT-PCR of aggrecan (b) and collagen II (c) in BMSCs within hydrogels during the first week of induced differentiation (normalized to the housekeeping gene GAPDH). (d, e) Representative Western blots for aggrecan and collagen II of BMSCs after induction of differentiation for 10 days (n=3), (*p<0.05, **p<0.01) (color online).

  • Table 1   Table 1 Reaction feeds, grafting ratios and grafting efficiencies of the PLG graft copolymers


    Molecules to begrafted (X)a)

    Reaction feed ratio: X/–COOH (mol/mol)

    Grafting ratiob)

    Grafting efficiencyb)












    RGD, Scram

    1:100, 1:100

    0.52%, 0.32%

    52%, 32%


    RGD, N-Cad

    1:100, 1:100

    0.49%, 0.3%

    49%, 30%

    X represents the molecule to be grafted; b) calculated by 1H NMR.


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