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Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials

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Abstract

Materials engineered to elicit targeted cellular responses in regenerative medicine must display bioligands with precise spatial and temporal control. Although materials with temporally regulated presentation of bioadhesive ligands using external triggers, such as light and electric fields, have recently been realized for cells in culture, the impact of in vivo temporal ligand presentation on cell–material responses is unknown. Here, we present a general strategy to temporally and spatially control the in vivo presentation of bioligands using cell-adhesive peptides with a protecting group that can be easily removed via transdermal light exposure to render the peptide fully active. We demonstrate that non-invasive, transdermal time-regulated activation of cell-adhesive RGD peptide on implanted biomaterials regulates in vivo cell adhesion, inflammation, fibrous encapsulation, and vascularization of the material. This work shows that triggered in vivo presentation of bioligands can be harnessed to direct tissue reparative responses associated with implanted biomaterials.

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Figure 1: Light-triggered activation of cell adhesion activity of caged RGD peptide on hydrogels.
Figure 2: Transdermal activation of in vivo inflammatory cell adhesion.
Figure 3: Light-triggered spatial patterning of in vivo cell adhesion.
Figure 4: Time-regulated in vivo activation of RGD peptide modulates fibrous encapsulation of implanted biomaterials.
Figure 5: Light-based activation of cell-adhesive peptide promotes vascularization of implanted biomaterials.

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Acknowledgements

This work was supported by the Materials World Network Program grants DFG AOBJ 569628 (AdC) and NSF DMR-0909002 (A.J.G.) and the National Institutes of Health (NIH) grants R01-AR062368 and R01-AR062920 (A.J.G.). T.T.L. and J.R.G. were supported by the Cell and Tissue Engineering NIH Biotechnology Training Grant (T32 GM-008433).

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Authors and Affiliations

  1. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA

    Ted T. Lee, José R. García, Ankur Singh, Edward A. Phelps, Asha Shekaran & Andrés J. García

  2. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA

    Ted T. Lee, José R. García, Ankur Singh, Edward A. Phelps, Asha Shekaran & Andrés J. García

  3. Max-Planck-Institut für Polymerforschung, Mainz 55128, Germany

    Julieta I. Paez, Simone Weis, Zahid Shafiq & Aránzazu del Campo

  4. Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York 14853, USA

    Ankur Singh

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  1. Ted T. Lee
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  2. José R. García
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  3. Julieta I. Paez
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  4. Ankur Singh
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  5. Edward A. Phelps
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  8. Asha Shekaran
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  10. Andrés J. García
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Contributions

T.T.L. and J.R.G. conducted all experiments, collected data and performed data analysis. J.I.P., S.W. and Z.S. synthesized and characterized caged compounds. A.S. performed the in vivo uncaging efficiency study, and A.S. and E.A.P. assisted with hydrogel development and implantation procedures. A.J.G. and A.d.C. developed the concept, and together with T.T.L. contributed to the planning and design of the project. T.T.L., A.d.C. and A.J.G. wrote the manuscript and all authors discussed the results and commented on the manuscript.

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Correspondence to Andrés J. García.

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The authors declare no competing financial interests.

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Lee, T., García, J., Paez, J. et al. Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials. Nature Mater 14, 352–360 (2015). https://doi.org/10.1038/nmat4157

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