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Responsive graphene oxide hydrogel microcarriers for controllable cell capture and release

智能响应性氧化石墨烯水凝胶微载体用于细胞的捕获与释放

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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.

摘要

细胞微载体作为生物医学领域中三维细胞培养的一个平台, 通常会由于过于简单的材料组成成分, 使得微载体的功能局限于细胞捕获与增殖. 本研究开发了一种近红外光响应的氧化石墨烯水凝胶微载体用于细胞的可控培养. 利用毛细管微流控技术, 通过乳化氧化石墨烯—异丙基丙烯酰胺—甲基化明胶复合预聚溶液来制备智能响应性氧化石墨烯水凝胶微载体. 氧化石墨烯对近红外光辐射的吸收能力, 异丙基丙烯酰胺的热响应性相转换能力, 以及甲基化明胶良好的生物相容性, 使得该复合水凝胶微载体具有高效的光热响应的细胞捕获、 增殖以及释放能力. 此外, 近红外光响应的氧化石墨烯水凝胶微载体还能够为其内部包裹的细胞提供保护, 使其免受免疫系统的攻击, 从而促进免疫活性小鼠体内肿瘤模型的形成与生长.

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References

  1. Wang L, Liu H, Zhang F, et al. Smart thin hydrogel coatings harnessing hydrophobicity and topography to capture and release cancer cells. Small, 2016, 12: 4697–4701

    Article  Google Scholar 

  2. Yuan B, Jin Y, Sun Y, et al. A strategy for depositing different types of cells in three dimensions to mimic tubular structures in tissues. Adv Mater, 2012, 24: 890–896

    Article  Google Scholar 

  3. Li Y, Liu W, Liu F, et al. Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia. Proc Natl Acad Sci USA, 2014, 111: 13511–13516

    Article  Google Scholar 

  4. Hu K, Zhou N, Li Y, et al. Sliced magnetic polyacrylamide hydrogel with cell-adhesive microarray interface: a novel multicellular spheroid culturing platform. ACS Appl Mater Interfaces, 2016, 8: 15113–15119

    Article  Google Scholar 

  5. Frey O, Misun PM, Fluri DA, et al. Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nat Commun, 2014, 5: 4250

    Article  Google Scholar 

  6. Wang W, Cui H, Zhang P, et al. Efficient capture of cancer cells by their replicated surfaces reveals multiscale topographic interactions coupled with molecular recognition. ACS Appl Mater Interfaces, 2017, 9: 10537–10543

    Article  Google Scholar 

  7. Huang C, Yang G, Ha Q, et al. Multifunctional “smart” particles engineered from live immunocytes: toward capture and release of cancer cells. Adv Mater, 2015, 27: 310–313

    Article  Google Scholar 

  8. Asghar W, El Assal R, Shafiee H, et al. Engineering cancer microenvironments for in vitro 3-D tumor models. Mater Today, 2015, 18: 539–553

    Article  Google Scholar 

  9. Liu X, Jin X, Ma PX. Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair. Nat Mater, 2011, 10: 398–406

    Article  Google Scholar 

  10. Liu Z, Shum HC. Fabrication of uniform multi-compartment particles using microfludic electrospray technology for cell coculture studies. Biomicrofluidics, 2013, 7: 044117

    Article  Google Scholar 

  11. Chan HF, Zhang Y, Leong KW. Efficient one-step production of microencapsulated hepatocyte spheroids with enhanced functions. Small, 2016, 12: 2720–2730

    Article  Google Scholar 

  12. Tang MYH, Shum HC. One-step immunoassay of C-reactive protein using droplet microfluidics. Lab Chip, 2016, 16: 4359–4365

    Article  Google Scholar 

  13. Griffin DR, Weaver WM, Scumpia PO, et al. Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks. Nat Mater, 2015, 14: 737–744

    Article  Google Scholar 

  14. Shang L, Cheng Y, Zhao Y. Emerging droplet microfluidics. Chem Rev, 2017, 117: 7964–8040

    Article  Google Scholar 

  15. Sun J, Zhang L, Wang J, et al. Tunable rigidity of (polymeric core)- (lipid shell) nanoparticles for regulated cellular uptake. Adv Mater, 2015, 27: 1402–1407

    Article  Google Scholar 

  16. Sim JY, Lee GH, Kim SH. Microfluidic design of magnetoresponsive photonic microcylinders with multicompartments. Small, 2015, 11: 4938–4945

    Article  Google Scholar 

  17. Lee SS, Kim B, Kim SK, et al. Robust microfluidic encapsulation of cholesteric liquid crystals toward photonic ink capsules. Adv Mater, 2015, 27: 627–633

    Article  Google Scholar 

  18. Yu Y, Fu F, Shang L, et al. Bioinspired helical microfibers from microfluidics. Adv Mater, 2017, 29: 1605765

    Article  Google Scholar 

  19. Liu W, Shang L, Zheng F, et al. Photonic crystal encoded microcarriers for biomaterial evaluation. Small, 2014, 10: 88–93

    Article  Google Scholar 

  20. Zhao Y, Shang L, Cheng Y, et al. Spherical colloidal photonic crystals. Acc Chem Res, 2014, 47: 3632–3642

    Article  Google Scholar 

  21. Wang J, Cheng Y, Yu Y, et al. Microfluidic generation of porous microcarriers for three-dimensional cell culture. ACS Appl Mater Interfaces, 2015, 7: 27035–27039

    Article  Google Scholar 

  22. Fu F, Shang L, Zheng F, et al. Cells cultured on core–shell photonic crystal barcodes for drug screening. ACS Appl Mater Interfaces, 2016, 8: 13840–13848

    Article  Google Scholar 

  23. Wang J, Zou M, Sun L, et al. Microfluidic generation of Buddha beads-like microcarriers for cell culture. Sci China Mater, 2017, 60: 857–865

    Article  Google Scholar 

  24. Wang J, Shang L, Cheng Y, et al. Microfluidic generation of porous particles encapsulating spongy graphene for oil absorption. Small, 2015, 11: 3890–3895

    Article  Google Scholar 

  25. Chen K, Li C, Shi L, et al. Growing three-dimensional biomorphic graphene powders using naturally abundant diatomite templates towards high solution processability. Nat Commun, 2016, 7: 13440

    Article  Google Scholar 

  26. Sun J, Chen Z, Yuan L, et al. Direct chemical-vapor-depositionfabricated, large-scale graphene glass with high carrier mobility and uniformity for touch panel applications. ACS Nano, 2016, 10: 11136–11144

    Article  Google Scholar 

  27. Wang J, Sun L, Zou M, et al. Bioinspired shape-memory graphene film with tunable wettability. Sci Adv, 2017, 3: e1700004

    Google Scholar 

  28. Cheng C, Wang D. Hydrogel-assisted transfer of graphene oxides into nonpolar organic media for oil decontamination. Angew Chem Int Ed, 2016, 55: 6853–6857

    Article  Google Scholar 

  29. Ma C, Le X, Tang X, et al. A multiresponsive anisotropic hydrogel with macroscopic 3D complex deformations. Adv Funct Mater, 2016, 26: 8670–8676

    Article  Google Scholar 

  30. Shang L, Wang Y, Yu Y, et al. Bio-inspired stimuli-responsive graphene oxide fibers from microfluidics. J Mater Chem A, 2017, 5: 15026–15030

    Article  Google Scholar 

  31. Yang Z, Ren J, Zhang Z, et al. Recent advancement of nanostructured carbon for energy applications. Chem Rev, 2015, 115: 5159–5223

    Article  Google Scholar 

  32. Li W, Wang J, Ren J, et al. 3D graphene oxide-polymer hydrogel: near-infrared light-triggered active scaffold for reversible cell capture and on-demand release. Adv Mater, 2013, 25: 6737–6743

    Article  Google Scholar 

  33. Ku SH, Lee M, Park CB. Carbon-based nanomaterials for tissue engineering. Adv Healthcare Mater, 2013, 2: 244–260

    Article  Google Scholar 

  34. Shi X, Chang H, Chen S, et al. Regulating cellular behavior on fewlayer reduced graphene oxide films with well-controlled reduction states. Adv Funct Mater, 2012, 22: 751–759

    Article  Google Scholar 

  35. Cheng C, Li S, Thomas A, et al. Functional graphene nanomaterials based architectures: biointeractions, fabrications, and emerging biological applications. Chem Rev, 2017, 117: 1826–1914

    Article  Google Scholar 

  36. Thompson BC, Murray E, Wallace GG. Graphite oxide to graphene. biomaterials to bionics. Adv Mater, 2015, 27: 7563–7582

    Article  Google Scholar 

  37. Li Y, Lu Q, Liu H, et al. Antibody-modified reduced graphene oxide films with extreme sensitivity to circulating tumor cells. Adv Mater, 2015, 27: 6848–6854

    Article  Google Scholar 

  38. Nichol JW, Koshy ST, Bae H, et al. Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials, 2010, 31: 5536–5544

    Article  Google Scholar 

  39. Cui H, Zhang P, Wang W, et al. Near-infrared (NIR) controlled reversible cell adhesion on a responsive nano-biointerface. Nano Res, 2017, 10: 1345–1355

    Article  Google Scholar 

Download references

Acknowledgements

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.

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Authors and Affiliations

  1. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China

    Jie Wang  (王洁), Ze Zhao  (赵泽), Lingyu Sun  (孙灵钰), Minhan Zou  (邹旻含) & Yuanjin Zhao  (赵远锦)

  2. Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China

    Guopu Chen  (陈国璞) & Jian’an Ren  (任建安)

Authors
  1. Jie Wang  (王洁)
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  2. Guopu Chen  (陈国璞)
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  3. Ze Zhao  (赵泽)
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  4. Lingyu Sun  (孙灵钰)
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  5. Minhan Zou  (邹旻含)
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  6. Jian’an Ren  (任建安)
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  7. Yuanjin Zhao  (赵远锦)
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Corresponding author

Correspondence to Yuanjin Zhao  (赵远锦).

Additional 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 bioinspired photonic nanomaterials.

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Wang, J., Chen, G., Zhao, Z. et al. Responsive graphene oxide hydrogel microcarriers for controllable cell capture and release. Sci. China Mater. 61, 1314–1324 (2018). https://doi.org/10.1007/s40843-018-9251-9

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  • DOI: https://doi.org/10.1007/s40843-018-9251-9

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