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Light-guiding hydrogels for cell-based sensing and optogenetic synthesis in vivo

Nature Photonics volume 7, pages 987–994 (2013)Cite this article

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Abstract

Polymer hydrogels are widely used as cell scaffolds for biomedical applications. Although the biochemical and biophysical properties of hydrogels have been investigated extensively, little attention has been paid to their potential photonic functionalities. Here, we report cell-integrated polyethylene glycol-based hydrogels for in vivo optical-sensing and therapy applications. Hydrogel patches containing cells were implanted in awake, freely moving mice for several days and shown to offer long-term transparency, biocompatibility, cell viability and light-guiding properties (loss of <1 dB cm−1). Using optogenetic, glucagon-like peptide-1 secreting cells, we conducted light-controlled therapy using the hydrogel in a mouse model with diabetes and obtained improved glucose homeostasis. Furthermore, real-time optical readout of encapsulated heat-shock-protein-coupled fluorescent reporter cells made it possible to measure the nanotoxicity of cadmium-based bare and shelled quantum dots (CdTe; CdSe/ZnS) in vivo.

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Figure 1: Schematic of a light-guiding hydrogel encapsulating cells for in vivo sensing and therapy.
Figure 2: Characteristics of hydrogels.
Figure 3: Light-guiding properties of fibre-optic hydrogels.
Figure 4: Hydrogel implants in vivo.
Figure 5: Cell-based sensing of nanocytotoxicity of quantum dots.
Figure 6: Optogenetic therapy in a mouse model of diabetes.

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References

  1. Miller-Jensen, K., Janes, K. A., Brugge, J. S. & Lauffenburger, D. A. Common effector processing mediates cell-specific responses to stimuli. Nature 448, 604–608 (2007).

    Article  ADS  Google Scholar 

  2. Pancrazio, J. J., Whelan, J. P., Borkholder, D. A., Ma, W. & Stenger, D. A. Development and application of cell-based biosensors. Ann. Biomed. Eng. 27, 697–711 (1999).

    Article  Google Scholar 

  3. Banerjee, P. & Bhunia, A. K. Mammalian cell-based biosensors for pathogens and toxins. Trends Biotechnol. 27, 179–188 (2009).

    Article  Google Scholar 

  4. El-Ali, J., Sorger, P. K. & Jensen, K. F. Cells on chips. Nature 442, 403–411 (2006).

    Article  ADS  Google Scholar 

  5. Zhang, F. et al. Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nature Protoc. 5, 439–456 (2010).

    Article  Google Scholar 

  6. Giepmans, B. N., Adams, S. R., Ellisman, M. H. & Tsien, R. Y. The fluorescent toolbox for assessing protein location and function. Science 312, 217–224 (2006).

    Article  ADS  Google Scholar 

  7. Rider, T. H. et al. AB cell-based sensor for rapid identification of pathogens. Sci. Signal. 301, 213–215 (2003).

    Google Scholar 

  8. Fenno, L., Yizhar, O. & Deisseroth, K. The development and application of optogenetics. Annu. Rev. Neurosci. 34, 389–412 (2011).

    Article  Google Scholar 

  9. Ye, H., Daoud-El Baba, M., Peng, R. W. & Fussenegger, M. A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science 332, 1565–1568 (2011).

    Article  ADS  Google Scholar 

  10. Wang, X., Chen, X. & Yang, Y. Spatiotemporal control of gene expression by a light-switchable transgene system. Nature Methods 9, 266–269 (2012).

    Article  Google Scholar 

  11. Toettcher, J. E., Gong, D., Lim, W. A. & Weiner, O. D. Light-based feedback for controlling intracellular signaling dynamics. Nature Methods 8, 837–839 (2011).

    Article  Google Scholar 

  12. Kim, M. et al. Maximal energy transport through disordered media with the implementation of transmission eigenchannels. Nature Photon. 6, 583–587 (2012).

    ADS  Google Scholar 

  13. Kwon, K., Son, T., Lee, K. J. & Jung, B. Enhancement of light propagation depth in skin: cross-validation of mathematical modeling methods. Lasers Med. Sci. 24, 605–615 (2009).

    Article  Google Scholar 

  14. Sparta, D. R. et al. Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits. Nature Protoc. 7, 12–23 (2012).

    Article  Google Scholar 

  15. Zhao, S. et al. Cell type-specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function. Nature Methods 8, 745–752 (2011).

    Article  Google Scholar 

  16. Hoffman, A. S. Hydrogels for biomedical applications. Adv. Drug Deliv. Rev. 54, 3–12 (2002).

    Article  Google Scholar 

  17. Jain, A., Yang, A. H. J. & Erickson, D. Gel-based optical waveguides with live cell encapsulation and integrated microfluidics. Opt. Lett. 37, 1472–1474 (2012).

    Article  ADS  Google Scholar 

  18. Wang, Y. et al. Biosensor based on hydrogel optical waveguide spectroscopy. Biosens. Bioelectr. 25, 1663–1668 (2010).

    Article  Google Scholar 

  19. Lee, S. C., Kwon, I. K. & Park, K. Hydrogels for delivery of bioactive agents: a historical perspective. Adv. Drug Deliv. Rev. 65, 17–20 (2013).

    Article  Google Scholar 

  20. Kloxin, A. M., Tibbitt, M. W. & Anseth, K. S. Synthesis of photodegradable hydrogels as dynamically tunable cell culture platforms. Nature Protoc. 5, 1867–1887 (2010).

    Article  Google Scholar 

  21. Tibbitt, M. W. & Anseth, K. S. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 103, 655–663 (2009).

    Article  Google Scholar 

  22. Lin, S., Sangaj, N., Razafiarison, T., Zhang, C. & Varghese, S. Influence of physical properties of biomaterials on cellular behavior. Pharm. Res. 28, 1422–1430 (2011).

    Article  Google Scholar 

  23. Choi, W. et al. Tomographic phase microscopy. Nature Methods 4, 717–719 (2007).

    Article  Google Scholar 

  24. Taniguchi, A. Live cell-based sensor cells. Biomaterials 31, 5911–5915 (2010).

    Article  Google Scholar 

  25. Drucker, D. J. Glucagon-like peptides. Diabetes 47, 159–169 (1998).

    Article  Google Scholar 

  26. Wang, Z. & Gleichmann, H. GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice. Diabetes 47, 50–56 (1998).

    Article  Google Scholar 

  27. Parker, S. T. et al. Biocompatible silk printed optical waveguides. Adv. Mater. 21, 2411–2415 (2009).

    Article  Google Scholar 

  28. Dupuis, A. et al. Prospective for biodegradable microstructured optical fibers. Opt. Lett. 32, 109–111 (2007).

    Article  ADS  Google Scholar 

  29. Wu, Y.-H., Park, H. B., Kai, T., Freeman, B. D. & Kalika, D. S. Water uptake, transport and structure characterization in poly(ethylene glycol) diacrylate hydrogels. J. Membr. Sci. 347, 197–208 (2010).

    Article  Google Scholar 

  30. Yu, L. & Ding, J. Injectable hydrogels as unique biomedical materials. Chem. Soc. Rev. 37, 1473–1481 (2008).

    Article  Google Scholar 

  31. Slaughter, B. V., Khurshid, S. S., Fisher, O. Z., Khademhosseini, A. & Peppas, N. A. Hydrogels in regenerative medicine. Adv. Mater. 21, 3307–3329 (2009).

    Article  Google Scholar 

  32. Murua, A. et al. Cell microencapsulation technology: towards clinical application. J. Control. Rel. 132, 76–83 (2008).

    Article  Google Scholar 

  33. Wurm, F. M. Production of recombinant protein therapeutics in cultivated mammalian cells. Nature Biotechnol. 22, 1393–1398 (2004).

    Article  Google Scholar 

  34. Eyrich, D. et al. Long-term stable fibrin gels for cartilage engineering. Biomaterials 28, 55–65 (2007).

    Article  Google Scholar 

  35. Sharma, B. et al. Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci. Transl. Med. 5, 167ra6 (2013).

    Article  Google Scholar 

  36. Holtz, J. H. & Asher, S. A. Polymerized colloidal crystal hydrogel films as intelligent chemical sensing materials. Nature 389, 829–832 (1997).

    Article  ADS  Google Scholar 

  37. Ge, S., Zhang, C., Zhu, Y., Yu, J. & Zhang, S. BSA activated CdTe quantum dot nanosensor for antimony ion detection. Analyst 135, 111–115 (2010).

    Article  ADS  Google Scholar 

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Acknowledgements

The authors thank M. Fussenegger and H. Ye (ETH) for providing plasmids for optogenetic experiments. This work was funded by the US National Institutes of Health (R21 EB013761), the US National Science Foundation (ECS-1101947), the US Department of Defense (FA9550-10-1-0537), the IT Consilience Creative Program of MKE and NIPA (C1515-1121-0003) and the Bio & Medical Technology Development Program and the World Class University Program of the Korean National Research Foundation (2012M3A9C6049791 and R31-2008-000-10071-0). S.N. acknowledges financial support from the Bullock–Wellman Fellowship.

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  1. Seok Hyun Yun

    Present address: Present address: Harvard University, 65 Lansdowne Street, UP-525, Cambridge, Massachusetts 02139, USA,

Authors and Affiliations

  1. Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, 50 Blossom Street, Boston, 02114, Massachusetts, USA

    Myunghwan Choi, Jin Woo Choi, Sedat Nizamoglu, Sei Kwang Hahn & Seok Hyun Yun

  2. WCU Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, 373-1 Guseong-dong, Yuseong-gu, Daejeon, Korea

    Myunghwan Choi, Seonghoon Kim & Seok Hyun Yun

  3. Department of Pharmacology, Wonkwang Institute of Interfused Biomedical Science, School of Dentistry, Wonkwang University, Seoul, Korea

    Jin Woo Choi

  4. Department of Materials Science and Engineering, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang, Korea

    Sei Kwang Hahn

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Contributions

M.C. and S.H.Y. designed the experiments. M.C. performed the experiments. J.W.C., S.K. and S.N. provided materials. M.C., S.K., S.K.H. and S.H.Y. analysed the data. M.C. and S.H.Y. wrote the manuscript, with input from all authors.

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Correspondence to Seok Hyun Yun.

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Choi, M., Choi, J., Kim, S. et al. Light-guiding hydrogels for cell-based sensing and optogenetic synthesis in vivo. Nature Photon 7, 987–994 (2013). https://doi.org/10.1038/nphoton.2013.278

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