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Nano Research

, Volume 11, Issue 10, pp 5573–5583 | Cite as

Cell membrane coating for reducing nanoparticle-induced inflammatory responses to scaffold constructs

  • Zhiyuan Fan
  • Peter Y. Li
  • Junjie Deng
  • Stephen C. Bady
  • Hao ChengEmail author
Research Article

Abstract

The controlled release of therapeutics from microparticles or nanoparticles (NPs) has been well-studied. Incorporation of these particles inside biomaterial scaffolds is promising for tissue regeneration and immune modulation. However, these particles may induce inflammatory and foreign body responses to scaffold constructs, limiting their applications. Here we show that widely used poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) formed by double emulsion dramatically increased neutrophil infiltration and pro-inflammatory cytokines in alginate scaffolds 1 day after the subcutaneous injection of the scaffolds into mice. The coating of red blood cell (RBC) membranes on PLGA NPs completely eliminated these short-term inflammatory responses. For a longer term of 10 days, neither PLGA NPs nor RBC membrane-coated NPs exerted a significant effect on the infiltration of neutrophils or macrophages in alginate scaffolds, possibly due to the degradation and/or clearance of NPs by infiltrating cells. Despite the extensive exploration of cell membrane-coated NPs, our study is the first to investigate the effects of cell membrane coating on foreign body reaction to NPs. By harnessing the natural biocompatibility of cell membranes, our strategy of anti-inflammatory protection for scaffolds may be pivotal for many applications such as those relying on the recruitment of stem cells and/or progenitor cells to scaffolds.

Keywords

regenerative medicine wound healing drug delivery endothelial cell immune tolerance 

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Notes

Acknowledgements

Research reported in this publication was supported by a faculty startup fund from Drexel University to H. C., a pilot grant from the Clinical & Translational Research Institute (CTRI), and National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R21AI133372. We would like to thank Dr. Elizabeth Blankenhorn and Dr. Frank Bearoff for their help on real-time PCR analysis.

References

  1. [1]
    Teng, Y. D.; Lavik, E. B.; Qu, X. L.; Park, K. I.; Ourednik, J.; Zurakowski, D.; Langer, R.; Snyder, E. Y. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc. Natl. Acad. Sci. USA 2002, 99, 3024–3029.CrossRefGoogle Scholar
  2. [2]
    Li, W. J.; Tuli, R.; Okafor, C.; Derfoul, A.; Danielson, K. G.; Hall, D. J.; Tuan, R. S. A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells. Biomaterials 2005, 26, 599–609.CrossRefGoogle Scholar
  3. [3]
    Ali, O. A.; Huebsch, N.; Cao, L.; Dranoff, G.; Mooney, D. J. Infection-mimicking materials to program dendritic cells in situ. Nat. Mater. 2009, 8, 151–158.CrossRefGoogle Scholar
  4. [4]
    Sheridan, M. H.; Shea, L. D.; Peters, M. C.; Mooney, D. J. Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery. J. Control. Release 2000, 64, 91–102.CrossRefGoogle Scholar
  5. [5]
    Lee, K. Y.; Peters, M. C.; Anderson, K. W.; Mooney, D. J. Controlled growth factor release from synthetic extracellular matrices. Nature 2000, 408, 998–1000.CrossRefGoogle Scholar
  6. [6]
    Lutolf, M. R.; Weber, F. E.; Schmoekel, H. G.; Schense, J. C.; Kohler, T.; Müller, R.; Hubbell, J. A. Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat. Biotechnol. 2003, 21, 513–518.CrossRefGoogle Scholar
  7. [7]
    Elbert, D. L.; Pratt, A. B.; Lutolf, M. P.; Halstenberg, S.; Hubbell, J. A. Protein delivery from materials formed by self-selective conjugate addition reactions. J. Control. Release 2001, 76, 11–25.CrossRefGoogle Scholar
  8. [8]
    Seliktar, D.; Zisch, A. H.; Lutolf, M. P.; Wrana, J. L.; Hubbell, J. A. MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing. J. Biomed. Mater. Res. A 2004, 68, 704–716.CrossRefGoogle Scholar
  9. [9]
    Martino, M. M.; Briquez, P. S.; Ranga, A.; Lutolf, M. P.; Hubbell, J. A. Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. Proc. Natl. Acad. Sci. USA 2013, 110, 4563–4568.CrossRefGoogle Scholar
  10. [10]
    Purcell, B. P.; Lobb, D.; Charati, M. B.; Dorsey, S. M.; Wade, R. J.; Zellars, K. N.; Doviak, H.; Pettaway, S.; Logdon, C. B.; Shuman, J. A. et al. Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition. Nat. Mater. 2014, 13, 653–661.CrossRefGoogle Scholar
  11. [11]
    Richardson, T. P.; Peters, M. C.; Ennett, A. B.; Mooney, D. J. Polymeric system for dual growth factor delivery. Nat. Biotechnol. 2001, 19, 1029–1034.CrossRefGoogle Scholar
  12. [12]
    Li, S. R.; Nih, L. R.; Bachman, H.; Fei, P.; Li, Y. L.; Nam, E.; Dimatteo, R.; Carmichael, S. T.; Barker, T. H.; Segura, T. Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability. Nat. Mater. 2017, 16, 953–961.CrossRefGoogle Scholar
  13. [13]
    Vacanti, N. M.; Cheng, H.; Hill, P. S.; Guerreiro, J. D. T.; Dang, T. T.; Ma, M. L.; Watson, S.; Hwang, N. S.; Langer, R.; Anderson, D. G. Localized delivery of dexamethasone from electrospun fibers reduces the foreign body response. Biomacromolecules 2012, 13, 3031–3038.CrossRefGoogle Scholar
  14. [14]
    Tan, Q.; Tang, H.; Hu, J. G.; Hu, Y. R.; Zhou, X. M.; Tao, Y. M.; Wu, Z. S. Controlled release of chitosan/heparin nanoparticle-delivered VEGF enhances regeneration of decellularized tissue-engineered scaffolds. Int. J. Nanomed. 2011, 6, 929–942.CrossRefGoogle Scholar
  15. [15]
    Holland, T. A.; Bodde, E. W. H.; Cuijpers, V. M. J. I.; Baggett, L. S.; Tabata, Y.; Mikos, A. G.; Jansen, J. A. Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair. Osteoarthritis Cartilage 2007, 15, 187–197.CrossRefGoogle Scholar
  16. [16]
    Hosseinkhani, H.; Hosseinkhani, M.; Gabrielson, N. P.; Pack, D. W.; Khademhosseini, A.; Kobayashi, H. DNA nanoparticles encapsulated in 3D tissue-engineered scaffolds enhance osteogenic differentiation of mesenchymal stem cells. J. Biomed. Mater. Res. A 2008, 85, 47–60.CrossRefGoogle Scholar
  17. [17]
    Hedberg, E. L.; Tang, A.; Crowther, R. S.; Carney, D. H.; Mikos, A. G. Controlled release of an osteogenic peptide from injectable biodegradable polymeric composites. J. Control. Release 2002, 84, 137–150.CrossRefGoogle Scholar
  18. [18]
    Verbeke, C. S.; Gordo, S.; Schubert, D. A.; Lewin, S. A.; Desai, R. M.; Dobbins, J.; Wucherpfennig, K. W.; Mooney, D. J. Multicomponent injectable hydrogels for antigenspecific tolerogenic immune modulation. Adv. Healthc. Mater. 2017, 6, 1600773.CrossRefGoogle Scholar
  19. [19]
    Gurtner, G. C.; Werner, S.; Barrandon, Y.; Longaker, M. T. Wound repair and regeneration. Nature 2008, 453, 314–321.CrossRefGoogle Scholar
  20. [20]
    Anderson, J. M.; Rodriguez, A.; Chang, D. T. Foreign body reaction to biomaterials. Semin. Immunol. 2008, 20, 86–100.CrossRefGoogle Scholar
  21. [21]
    Anderson, J. M. Biological responses to materials. Ann. Rev. Mater. Res. 2001, 31, 81–110.CrossRefGoogle Scholar
  22. [22]
    Anderson, J. M.; McNally, A. K. Biocompatibility of implants: Lymphocyte/macrophage interactions. Semin. Immunopathol. 2011, 33, 221–233.CrossRefGoogle Scholar
  23. [23]
    Kim, Y. K.; Chen, E. Y.; Liu, W. F. Biomolecular strategies to modulate the macrophage response to implanted materials. J. Mater. Chem. B 2016, 4, 1600–1609.CrossRefGoogle Scholar
  24. [24]
    Zhang, L.; Cao, Z. Q.; Bai, T.; Carr, L.; Ella-Menye, J. R.; Irvin, C.; Ratner, B. D.; Jiang, S. Y. Zwitterionic hydrogels implanted in mice resist the foreign-body reaction. Nat. Biotechnol. 2013, 31, 553–556.CrossRefGoogle Scholar
  25. [25]
    Vegas, A. J.; Veiseh, O.; Doloff, J. C.; Ma, M. L.; Tam, H. H.; Bratlie, K.; Li, J.; Bader, A. R.; Langan, E.; Olejnik, K. et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat. Biotechnol. 2016, 34, 345–352.CrossRefGoogle Scholar
  26. [26]
    Chen, E. Y.; Chu, S. H.; Gov, L.; Kim, Y. K.; Lodoen, M. B.; Tenner, A. J.; Liu, W. F. CD200 modulates macrophage cytokine secretion and phagocytosis in response to poly(lacticco-glycolic acid) microparticles and films. J. Mat. Chem. B 2017, 5, 1574–1584.CrossRefGoogle Scholar
  27. [27]
    Wu, Y. Q.; Qu, H. C.; Sfyroera, G.; Tzekou, A.; Kay, B. K.; Nilsson, B.; Ekdahl, K. N.; Ricklin, D.; Lambris, J. D. Correction: Protection of nonself surfaces from complement attack by factor H-binding peptides: Implications for therapeutic medicine. J. Immunol. 2012, 188, 6425.CrossRefGoogle Scholar
  28. [28]
    Hu, C. M. J.; Zhang, L.; Aryal, S.; Cheung, C.; Fang, R. H.; Zhang, L. F. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc. Natl. Acad. Sci. USA 2011, 108, 10980–10985.CrossRefGoogle Scholar
  29. [29]
    Hu, C. M. J.; Fang, R. H.; Wang, K. C.; Luk, B. T.; Thamphiwatana, S.; Dehaini, D.; Nguyen, P.; Angsantikul, P.; Wen, C. H.; Kroll, A. V. et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 2015, 526, 118–121.CrossRefGoogle Scholar
  30. [30]
    Hu, Q. Y.; Sun, W. J.; Qian, C. G.; Wang, C.; Bomba, H. N.; Gu, Z. Anticancer platelet-mimicking nanovehicles. Adv. Mater. 2015, 27, 7043–7050.CrossRefGoogle Scholar
  31. [31]
    Gao, M.; Liang, C.; Song, X. J.; Chen, Q.; Jin, Q. T.; Wang, C.; Liu, Z. Erythrocyte-membrane-enveloped perfluorocarbon as nanoscale artificial red blood cells to relieve tumor hypoxia and enhance cancer radiotherapy. Adv. Mater. 2017, 29, 1701429.CrossRefGoogle Scholar
  32. [32]
    Fan, Z. Y.; Zhou, H.; Li, P. Y.; Speer, J. E.; Cheng, H. Structural elucidation of cell membrane-derived nanoparticles using molecular probes. J. Mater. Chem. B 2014, 2, 8231–8238.CrossRefGoogle Scholar
  33. [33]
    Zhou, H.; Fan, Z. Y.; Lemons, P. K.; Cheng, H. A facile approach to functionalize cell membrane-coated nanoparticles. Theranostics 2016, 6, 1012–1022.CrossRefGoogle Scholar
  34. [34]
    Fang, R. H.; Hu, C. M. J.; Luk, B. T.; Gao, W. W.; Copp, J. A.; Tai, Y. Y.; O'Connor, D. E.; Zhang, L. F. Cancer cell membrane-coated nanoparticles for anticancer vaccination and drug delivery. Nano Lett. 2014, 14, 2181–2188.CrossRefGoogle Scholar
  35. [35]
    Xuan, M. J.; Shao, J. X.; Zhao, J.; Li, Q.; Dai, L. R.; Li, J. B. Magnetic mesoporous silica nanoparticles cloaked by red blood cell membranes: Applications in cancer therapy. Angew. Chem., Int. Ed., in press, DOI: 10.1002/anie.201712996.Google Scholar
  36. [36]
    Li, P. Y.; Fan, Z. Y.; Cheng, H. Cell membrane bioconjugation and membrane-derived nanomaterials for immunotherapy. Bioconjug. Chem. 2018, 29, 624–634.CrossRefGoogle Scholar
  37. [37]
    Fang, R. H.; Kroll, A. V.; Gao, W. W.; Zhang, L. F. Cell membrane coating nanotechnology. Adv. Mater., in press, DOI: 10.1002/adma.201706759.Google Scholar
  38. [38]
    Oldenborg, P. A.; Zheleznyak, A.; Fang, Y. F.; Lagenaur, C. F.; Gresham, H. D.; Lindberg, F. P. Role of CD47 as a marker of self on red blood cells. Science 2000, 288, 2051–2054.CrossRefGoogle Scholar
  39. [39]
    Bencherif, S. A.; Sands, R. W.; Bhatta, D.; Arany, P.; Verbeke, C. S.; Edwards, D. A.; Mooney, D. J. Injectable preformed scaffolds with shape-memory properties. Proc. Natl. Acad. Sci. USA 2012, 109, 19590–19595.CrossRefGoogle Scholar
  40. [40]
    Copp, J. A.; Fang, R. H.; Luk, B. T.; Hu, C. M. J.; Gao, W. W.; Zhang, K.; Zhang, L. F. Clearance of pathological antibodies using biomimetic nanoparticles. Proc. Natl. Acad. Sci. USA 2014, 111, 13481–13486.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Zhiyuan Fan
    • 1
  • Peter Y. Li
    • 1
  • Junjie Deng
    • 1
    • 2
  • Stephen C. Bady
    • 1
  • Hao Cheng
    • 1
    Email author
  1. 1.Department of Materials Science and EngineeringDrexel UniversityPhiladelphiaUSA
  2. 2.Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou Institute of Biomaterials and EngineeringChinese Academy of SciencesWenzhouChina

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