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SCIENCE CHINA Materials, Volume 61, Issue 10: 1314-1324(2018) https://doi.org/10.1007/s40843-018-9251-9

Responsive graphene oxide hydrogel microcarriers for controllable cell capture and release

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  • ReceivedFeb 3, 2018
  • AcceptedMar 14, 2018
  • PublishedApr 12, 2018

Abstract

Cell microcarriers have emerged as a powerful cell culture platform in biomedical areas, but their functions are usually limited to simply capturing and proliferating cells, because of the simplicity of their components. Thus, in this study, we developed a new near-infrared (NIR) light-responsive graphene oxide (GO) hydrogel microcarrier system for controllable cell culture. The microcarriers were generated by using capillary microfluidics to emulsify the GO dispersed poly(N-isopropylacrylamide) (pNIPAM) and gelatin methacrylate (GelMA) pre-gel solution. The composite GO hydrogel microcarriers exhibited photothermally responsive cell capture, as well as the capacity for proliferation and release due to the NIR absorption of GO, the thermally responsive shape transition of pNIPAM, and the high biocompatibility of GelMA. It was found that the NIR-responsive GO hydrogel microcarriers could prevent the cultured cells from being attacked by the immune system and promote the formation of tumor models in immunocompetent mice, which is desired for tumor and drug research. These features make the NIR-responsive GO hydrogel microcarriers excellent functional materials for different biomedical applications.


Funded by

the National Natural Science Foundation of China(21473029,51522302)

the NSAF Foundation of China(U1530260)

the Scientific Research Foundation of Southeast University

the Scientific Research Foundation of Graduate School of Southeast University(YBJJ1625)

and the Postgraduate Education Reform Project of Jiangsu Province(KYCX17_0154)


Acknowledgment

This work was supported by the National Natural Science Foundation of China (21473029 and 51522302), the NSAF Foundation of China (U1530260), the Scientific Research Foundation of Southeast University, the Scientific Research Foundation of Graduate School of Southeast University, and the Postgraduate Research & Practice Innovation Program of Jiangsu Province and the Fundamental Research Funds for the Central Universities.


Interest statement

The authors declare no conflict of interest.


Contributions statement

Wang J carried out the materials preparation and in vitro experiments; Chen G carried out the in vivo experiments; Zhao Y conceived the idea and designed the experiment; Wang J and Zhao Y analyzed data and wrote the paper; all authors contributed to general discussion of the article.


Author information

Jie Wang received her BSc degree from Southeast University in 2014. She is now a PhD candidate under the supervision of Prof. Yuanjin Zhao at Southeast University. Her research interest is the fabrication of functional materials based on microfluidics.


Yuanjin Zhao received his PhD degree in 2011 from Southeast University. In 2009–2010, he worked as a research scholar at Prof. David A. Weitz’s group in SEAS of Harvard University. Since 2015, he was promoted to be a full professor of Southeast University. His current scientific interests include microfluidic-based materials fabrication, biosensors, and bio-inspired photonic nanomaterials.


Supplement

Supplementary information

Supporting data are available in the online version of the paper.


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  • Figure 1

    (a) The thermoresponsive behaviors of the jellyfish-shaped GO composite hydrogels with the temperature increasing. The concentration ratios of NIPAM:AAm in the composite hydrogels were 100%:0%, 97.5%:2.5%, 95%:5%, and 92.5%:7.5% from left to right, respectively. The scale bar is 5 mm. (b) The volume ratios of the corresponding composite hydrogels in (a) at different temperature.

  • Scheme 1

    (a) Schematic diagram of the NIR-responsive GO hydrogel microcarriers for controllable cell capture and release; (b) the responsive GO hydrogel microcarriers promote the formation of tumor models in immunocompetent mice with the NIR irradiation.

  • Figure 2

    (a) Schematic diagram of microfluidic generation of responsive GO hydrogel microcarriers. (b–d) The optical microscopic images of the GO hydrogel microcarriers before, under, and after NIR irradiation, respectively. The scale bars are 1 mm. (e) The volume change of GO hydrogel microcarriers with different concentration of GO under different power intensity of NIR. (f) The volume variation of GO hydrogel microcarriers as a function of the cycle number.

  • Figure 3

    (a, b) Fluorescent images of (a) escaped cells and (b) released cells from the microcarriers. (c–h) The progress of NIR-stimulated cell release from the microcarrier during several cycles. (i, j) The percentage of released cells with different irradiation period and laser power intensity, respectively. The scale bars are 150 µm in (a, b) and 500 µm in (c–h).

  • Figure 4

    (a) The progress of injecting microcarriers loaded with Hepa1-6 cells into the armpits of mice and releasing cells subsequently by NIR. (b) The progress of the temperature change of the model under NIR irradiation.

  • Figure 5

    (a) The comparison of the tumor proliferation and angiogenesis in three groups, determined by H&E, Ki67 and CD31 staining. The vessels are pointed with the yellow arrows. (b) Quantification of the tumor weight in three groups. The colors of the tumors are not uniform for different mice due to the random encapsulation of the black microcarriers in the tumors. (c) Quantification of Ki67 and CD31 staining shown by the positively stained cells density and blood vessel density, respectively. Results are presented as mean value ± standard error in (b) and (c).

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