Designing natural and synthetic immune tissues

Abstract

Vaccines and immunotherapies have provided enormous improvements for public health, but there are fundamental disconnects between where most studies are performed—in cell culture and animal models—and the ultimate application in humans. Engineering immune tissues and organs, such as bone marrow, thymus, lymph nodes and spleen, could be instrumental in overcoming these hurdles. Fundamentally, designed immune tissues could serve as in vitro tools to more accurately study human immune function and disease, while immune tissues engineered for implantation as next-generation vaccines or immunotherapies could enable direct, on-demand control over generation and regulation of immune function. In this Review, we discuss recent interdisciplinary strategies that are merging materials science and immunology to create engineered immune tissues in vitro and in vivo. We also highlight the hurdles facing these approaches and the need for comparison to existing clinical options, relevant animal models, and other emerging technologies.

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Fig. 1: Immune tissues play distinct roles in immune cell development.
Fig. 2: Immune organoids allow for the development of germinal-centre-like B cells that undergo complex immunological processes.
Fig. 3: Engineered bone marrow on-a-chip replicates function of bone marrow in vivo.
Fig. 4: Engineered scaffolds recruit APCs to access tumour antigen and improve function after migration to LNs.
Fig. 5: Local changes in lymph node structure from direct injection of tolerogenic microparticles into the lymph nodes of mice with autoimmune disease drive systemic changes in immune signalling.
Fig. 6: Engineering immune tissues can restore immune functions in vivo.
Fig. 7: New immunological insight informs immune tissue engineering design.

References

  1. 1.

    Lesokhin, A. M., Callahan, M. K., Postow, M. A. & Wolchok, J. D. On being less tolerant: enhanced cancer immunosurveillance enabled by targeting checkpoints and agonists of T cell activation. Sci. Transl. Med. 7, 280sr281 (2015).

    Article  CAS  Google Scholar 

  2. 2.

    Chen, D. S. & Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature 541, 321–330 (2017).

    Article  CAS  Google Scholar 

  3. 3.

    DeFrancesco, L. CAR-T’s forge ahead, despite Juno deaths. Nat. Biotechnol. 35, 6–7 (2017).

    Article  CAS  Google Scholar 

  4. 4.

    Cadavid, D. et al. Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 16, 189–199 (2017).

    Article  CAS  Google Scholar 

  5. 5.

    Antonelli, A. et al. Establishing human leukemia xenograft mouse models by implanting human bone marrow-like scaffold-based niches. Blood 128, 2949–2959 (2016).

    Article  CAS  Google Scholar 

  6. 6.

    Kapsenberg, M. L. Dendritic-cell control of pathogen-driven T-cell polarization. Nat. Rev. Immunol. 3, 984–993 (2003).

    Article  CAS  Google Scholar 

  7. 7.

    Loder, F. et al. B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals. J. Exp. Med. 190, 75–89 (1999).

    Article  CAS  Google Scholar 

  8. 8.

    Nemazee, D. Mechanisms of central tolerance for B cells. Nat. Rev. Immunol. 17, 281–294 (2017).

    Article  CAS  Google Scholar 

  9. 9.

    Hogquist, K. A., Baldwin, T. A. & Jameson, S. C. Central tolerance: Learning self-control in the thymus. Nat. Rev. Immunol. 5, 772–782 (2005).

    Article  CAS  Google Scholar 

  10. 10.

    Takahama, Y. Journey through the thymus: stromal guides for T-cell development and selection. Nat. Rev. Immunol. 6, 127–135 (2006).

    Article  CAS  Google Scholar 

  11. 11.

    Mebius, R. E. & Kraal, G. Structure and function of the spleen. Nat. Rev. Immunol. 5, 606–616 (2005).

    Article  CAS  Google Scholar 

  12. 12.

    Butcher, E. C. & Picker, L. J. Lymphocyte homing and homeostasis. Science 272, 60–66 (1996).

    Article  CAS  Google Scholar 

  13. 13.

    Nutt, S. L., Hodgkin, P. D., Tarlinton, D. M. & Corcoran, L. M. The generation of antibody-secreting plasma cells. Nat. Rev. Immunol. 15, 160–171 (2015).

    Article  CAS  Google Scholar 

  14. 14.

    Crotty, S. Follicular helper CD4 T cells (T-FH). Annu. Rev. Immunol. 29, 621–663 (2011).

    Article  CAS  Google Scholar 

  15. 15.

    Bhatia, S. N. & Ingber, D. E. Microfluidic organs-on-chips. Nat. Biotechnol. 32, 760–772 (2014).

    Article  CAS  Google Scholar 

  16. 16.

    Takebe, T., Zhang, B. Y. & Radisic, M. Synergistic engineering: Organoids meet organs-on-a-chip. Cell Stem Cell 21, 297–300 (2017).

    Article  CAS  Google Scholar 

  17. 17.

    Sardi, M., Lubitz, A. & Giese, C. Modeling human immunity in vitro: improving artificial lymph node physiology by stromal cells. Appl. In Vitro Toxicol. 2, 143–150 (2016).

    Article  CAS  Google Scholar 

  18. 18.

    Nojima, T. et al. In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo. Nat. Commun. 2, 465 (2011).

    Article  CAS  Google Scholar 

  19. 19.

    Kuzin, I. et al. Long-term immunologically competent human peripheral lymphoid tissue cultures in a 3D bioreactor. Biotechnol. Bioeng. 108, 1430–1440 (2011).

    Article  CAS  Google Scholar 

  20. 20.

    Tomei, A. A., Siegert, S., Britschgi, M. R., Luther, S. A. & Swartz, M. A. Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment. J. Immunol. 183, 4273–4283 (2009).

    Article  CAS  Google Scholar 

  21. 21.

    Singh, A. Biomaterials innovation for next generation ex vivo immune tissue engineering. Biomaterials 130, 104–110 (2017).

    Article  CAS  Google Scholar 

  22. 22.

    Purwada, A. et al. Ex vivo engineered immune organoids for controlled germinal center reactions. Biomaterials 63, 24–34 (2015).

    Article  CAS  Google Scholar 

  23. 23.

    Purwada, A. & Singh, A. Immuno-engineered organoids for regulating the kinetics of B-cell development and antibody production. Nat. Protoc. 12, 168–182 (2017).

    Article  CAS  Google Scholar 

  24. 24.

    Beguelin, W. et al. EZH2 enables germinal centre formation through epigenetic silencing of CDKN1A and an Rb-E2F1 feedback loop. Nat. Commun. 8, 877 (2017).

    Article  CAS  Google Scholar 

  25. 25.

    Poznansky, M. C. et al. Efficient generation of human T cells from a tissue-engineered thymic organoid. Nat. Biotechnol. 18, 729–734 (2000).

    Article  CAS  Google Scholar 

  26. 26.

    Lee, J. & Kotov, N. A. Notch ligand presenting acellular 3D microenvironments for ex vivo human hematopoietic stem-cell culture made by layer-by-layer assembly. Small 5, 1008–1013 (2009).

    Article  CAS  Google Scholar 

  27. 27.

    Pinto, S. et al. An organotypic coculture model supporting proliferation and differentiation of medullary thymic epithelial cells and promiscuous gene expression. J. Immunol. 190, 1085–1093 (2013).

    Article  CAS  Google Scholar 

  28. 28.

    Nichols, J. E. et al. In vitro analog of human bone marrow from 3D scaffolds with biomimetic inverted colloidal crystal geometry. Biomaterials 30, 1071–1079 (2009).

    Article  CAS  Google Scholar 

  29. 29.

    Cook, M. M. et al. Micromarrows-three-dimensional coculture of hematopoietic stem cells and mesenchymal stromal cells. Tissue Eng. Part C 18, 319–328 (2012).

    Article  CAS  Google Scholar 

  30. 30.

    Torisawa, Y. S. et al. Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nat. Methods 11, 663–669 (2014).

    Article  CAS  Google Scholar 

  31. 31.

    Tao, Z. M. & Ghoroghchian, P. P. Microparticle, nanoparticle, and stem cell-based oxygen carriers as advanced blood substitutes. Trends Biotechnol. 32, 466–473 (2014).

    Article  CAS  Google Scholar 

  32. 32.

    Giarratana, M. C. et al. Proof of principle for transfusion of in vitro-generated red blood cells. Blood 118, 5071–5079 (2011).

    Article  CAS  Google Scholar 

  33. 33.

    Thon, J. N. et al. Platelet bioreactor-on-a-chip. Blood 124, 1857–1867 (2014).

    Article  CAS  Google Scholar 

  34. 34.

    Trakarnsanga, K. et al. An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells. Nat. Commun. 8, 14750 (2017).

    Article  CAS  Google Scholar 

  35. 35.

    Kim, S. K., Moon, W. K., Park, J. Y. & Jung, H. Inflammatory mimetic microfluidic chip by immobilization of cell adhesion molecules for T cell adhesion. Analyst 137, 4062–4068 (2012).

    Article  CAS  Google Scholar 

  36. 36.

    Stachowiak, A. N. & Irvine, D. J. Inverse opal hydrogel-collagen composite scaffolds as a supportive microenvironment for immune cell migration. J. Biomed. Mater. Res. 85A, 815–828 (2008).

    Article  CAS  Google Scholar 

  37. 37.

    Haessler, U., Pisano, M., Wu, M. M. & Swartz, M. A. Dendritic cell chemotaxis in 3D under defined chemokine gradients reveals differential response to ligands CCL21 and CCL19. Proc. Natl Acad. Sci. USA 108, 5614–5619 (2011).

    Article  Google Scholar 

  38. 38.

    Gopalakrishnan, N. et al. Infection and immunity on a chip: a compartmentalised microfluidic platform to monitor immune cell behaviour in real time. Lab Chip 15, 1481–1487 (2015).

    Article  CAS  Google Scholar 

  39. 39.

    Jones, C. N. et al. Microfluidic chambers for monitoring leukocyte trafficking and humanized nano-proresolving medicines interactions. Proc. Natl Acad. Sci. USA 109, 20560–20565 (2012).

    Article  Google Scholar 

  40. 40.

    Dura, B. et al. Profiling lymphocyte interactions at the single-cell level by microfluidic cell pairing. Nat. Commun. 6, 5940 (2015).

    Article  CAS  Google Scholar 

  41. 41.

    Rosa, P. M., Gopalakrishnan, N., Ibrahim, H., Haug, M. & Halaas, O. The intercell dynamics of T cells and dendritic cells in a lymph node-on-a-chip flow device. Lab Chip 16, 3728–3740 (2016).

    Article  CAS  Google Scholar 

  42. 42.

    Ross, A. E., Belanger, M. C., Woodroof, J. F. & Pompano, R. R. Spatially resolved microfluidic stimulation of lymphoid tissue ex vivo. Analyst 142, 649–659 (2017).

    Article  CAS  Google Scholar 

  43. 43.

    Hori, Y., Winans, A. M., Huang, C. C., Horrigan, E. M. & Irvine, D. J. Injectable dendritic cell-carrying alginate gels for immunization and immunotherapy. Biomaterials 29, 3671–3682 (2008).

    Article  CAS  Google Scholar 

  44. 44.

    Ali, O. A., Huebsch, N., Cao, L., Dranoff, G. & Mooney, D. J. Infection-mimicking materials to program dendritic cells in situ. Nat. Mater. 8, 151–158 (2009).

    Article  CAS  Google Scholar 

  45. 45.

    Ali, O. A., Emerich, D., Dranoff, G. & Mooney, D. J. In situ regulation of DC subsets and T cells mediates tumour regression in mice. Sci. Transl. Med. 1, 8ra19 (2009).

    Article  CAS  Google Scholar 

  46. 46.

    Kim, J. et al. Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat. Biotechnol. 33, 64–72 (2015).

    Article  CAS  Google Scholar 

  47. 47.

    Verbeke, C. S. et al. Multicomponent injectable hydrogels for antigen-specific tolerogenic immune modulation. Adv. Healthc. Mater 6, 1600773 (2017).

    Article  CAS  Google Scholar 

  48. 48.

    Irvine, D. J., Swartz, M. A. & Szeto, G. L. Engineering synthetic vaccines using cues from natural immunity. Nat. Mater. 12, 978–990 (2013).

    Article  CAS  Google Scholar 

  49. 49.

    Cheung, A. S. & Mooney, D. J. Engineered materials for cancer immunotherapy. Nano Today 10, 511–531 (2015).

    Article  CAS  Google Scholar 

  50. 50.

    Northrup, L., Christopher, M. A., Sullivan, B. P. & Berkland, C. Combining antigen and immunomodulators: Emerging trends in antigen-specific immunotherapy for autoimmunity. Adv. Drug Deliv. Rev. 98, 86–98 (2016).

    Article  CAS  Google Scholar 

  51. 51.

    Tostanoski, L. H. & Jewell, C. M. Engineering self -assembled materials to study and direct immune function. Adv. Drug Deliv. Rev. 114, 60–78 (2017).

    Article  CAS  Google Scholar 

  52. 52.

    Pearson, R. M., Casey, L. M., Hughes, K. R., Miller, S. D. & Shea, L. D. In vivo reprogramming of immune cells: Technologies for induction of antigen-specific tolerance. Adv. Drug Deliv. Rev. 114, 240–255 (2017).

    Article  CAS  Google Scholar 

  53. 53.

    Kuai, R., Ochyl, L. J., Bahjat, K. S., Schwendeman, A. & Moon, J. J. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat. Mater. 16, 489–496 (2017).

    Article  CAS  Google Scholar 

  54. 54.

    Ishihara, J. et al. Matrix-binding checkpoint immunotherapies enhance antitumour efficacy and reduce adverse events. Sci. Transl. Med. 9, eaan0401 (2017).

    Article  Google Scholar 

  55. 55.

    Jewell, C. M., Lopez, S. C. B. & Irvine, D. J. In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles. Proc. Natl Acad. Sci. USA 108, 15745–15750 (2011).

    Article  Google Scholar 

  56. 56.

    Gammon, J. M. et al. Low-dose controlled release of mTOR inhibitors maintains T cell plasticity and promotes central memory T cells. J. Control Release 263, 151–161 (2017).

    Article  CAS  Google Scholar 

  57. 57.

    Ludvigsson, J., Wahlberg, J. & Casas, R. Intralymphatic injection of autoantigen in type 1 diabetes. New Engl. J. Med. 376, 697–699 (2017).

    Article  Google Scholar 

  58. 58.

    Tostanoski, L. H. et al. Reprogramming the local lymph node microenvironment promotes tolerance that is systemic and antigen specific. Cell Reports 16, 2940–2952 (2016).

    Article  CAS  Google Scholar 

  59. 59.

    Ugel, S. et al. In vivo administration of artificial antigen-presenting cells activates low-avidity t cells for treatment of cancer. Cancer Res. 69, 9376–9384 (2009).

    Article  CAS  Google Scholar 

  60. 60.

    Perica, K. et al. Enrichment and expansion with nanoscale artificial antigen presenting cells for adoptive immunotherapy. ACS Nano 9, 6861–6871 (2015).

    Article  CAS  Google Scholar 

  61. 61.

    Sunshine, J. C., Perica, K., Schneck, J. P. & Green, J. J. Particle shape dependence of CD8+T cell activation by artificial antigen presenting cells. Biomaterials 35, 269–277 (2014).

    Article  CAS  Google Scholar 

  62. 62.

    Meyer, R. A. et al. Biodegradable nanoellipsoidal artificial antigen presenting cells for antigen specific T-Cell activation. Small 11, 1519–1525 (2015).

    Article  CAS  Google Scholar 

  63. 63.

    Bruns., H. et al. CD47 enhances in vivo functionality of artificial antigen-presenting cells. Clin. Cancer Res. 21, 2075–2083 (2015).

    Article  CAS  Google Scholar 

  64. 64.

    Kosmides, A. K. et al. Biomimetic biodegradable artificial antigen presenting with PD-1 blockade to treat melanoma cells synergize. Biomaterials 118, 16–26 (2017).

    Article  CAS  Google Scholar 

  65. 65.

    Cuzzone, D. A., Albano, N. J., Aschen, S. Z., Ghanta, S. & Mehrara, B. J. Decellularized lymph nodes as scaffolds for tissue engineered lymph nodes. Lymphat. Res. Biol 13, 186–194 (2015).

    Article  CAS  Google Scholar 

  66. 66.

    Suematsu, S. & Watanabe, T. Generation of a synthetic lymphoid tissue-like organoid in mice. Nat. Biotechnol. 22, 1539–1545 (2004).

    Article  CAS  Google Scholar 

  67. 67.

    Okamoto, N., Chihara, R., Shimizu, C., Nishimoto, S. & Watanabe, T. Artificial lymph nodes induce potent secondary immune responses in naive and immunodeficient mice. J. Clin. Invest. 117, 997–1007 (2007).

    Article  CAS  Google Scholar 

  68. 68.

    Kobayashi, Y. & Watanabe, T. Gel-trapped lymphorganogenic chemokines trigger artificial tertiary lymphoid organs and mount adaptive immune responses in vivo. Front. Immunol 7, 316 (2016).

    Article  CAS  Google Scholar 

  69. 69.

    Stephan, S. B. et al. Biopolymer implants enhance the efficacy of adoptive T-cell therapy. Nat. Biotechnol. 33, 97–101 (2015).

    Article  CAS  Google Scholar 

  70. 70.

    Smith, T. T. et al. Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumours. J. Clin. Invest 127, 2176–2191 (2017).

    Article  Google Scholar 

  71. 71.

    Smith, T. T. et al. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nat. Nanotech 12, 813–820 (2017).

    Article  CAS  Google Scholar 

  72. 72.

    Hun, M. et al. Native thymic extracellular matrix improves in vivo thymic organoid T cell output, and drives in vitro thymic epithelial cell differentiation. Biomaterials 118, 1–15 (2017).

    Article  CAS  Google Scholar 

  73. 73.

    Fan, Y. et al. Bioengineering thymus organoids to restore thymic function and induce donor-specific immune tolerance to allografts. Mol. Ther. 23, 1262–1277 (2015).

    Article  CAS  Google Scholar 

  74. 74.

    Markert, M. L., Devlin, B. H. & McCarthy, E. A. Thymus transplantation. Clin. Immunol. 135, 236–246 (2010).

    Article  CAS  Google Scholar 

  75. 75.

    Mao, A. S. et al. Deterministic encapsulation of single cells in thin tunable microgels for niche modelling and therapeutic delivery. Nat. Mater. 16, 236–243 (2017).

    Article  CAS  Google Scholar 

  76. 76.

    Lee, J. et al. Implantable microenvironments to attract hematopoietic stem/cancer cells. Proc. Natl Acad. Sci. USA 109, 19638–19643 (2012).

    Article  Google Scholar 

  77. 77.

    Shih, Y.-R. et al. In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism. Proc. Natl Acad. Sci. USA 114, 5419–5424 (2017).

    Article  CAS  Google Scholar 

  78. 78.

    Holzapfel, B. M. et al. Tissue engineered humanized bone supports human hematopoiesis in vivo. Biomaterials 61, 103–114 (2015).

    Article  CAS  Google Scholar 

  79. 79.

    Reinisch, A. et al. A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells. Nat. Med 22, 812–821 (2016).

    Article  CAS  Google Scholar 

  80. 80.

    Abarrategi, A. et al. Versatile humanized niche model enables study of normal and malignant human hematopoiesis. J. Clin. Invest 127, 543–548 (2017).

    Article  Google Scholar 

  81. 81.

    Ben-David, U. et al. Patient-derived xenografts undergo mouse-specific tumour evolution. Nat. Genet. 49, 1567–1575 (2017).

    Article  CAS  Google Scholar 

  82. 82.

    Schaupper, M., Jeltsch, M., Rohringer, S., Redl, H. & Holnthoner, W. Lymphatic vessels in regenerative medicine and tissue engineering. Tissue Eng. Part B 22, 395–407 (2016).

    Article  CAS  Google Scholar 

  83. 83.

    Randolph, G. J., Ivanov, S., Zinselmeyer, B. H. & Scallan, J. P. The lymphatic system: integral roles in immunity. Annu. Rev. Immunol. 35, 31–52 (2017).

    Article  CAS  Google Scholar 

  84. 84.

    Gibot, L. et al. Tissue-engineered 3D human lymphatic microvascular network for in vitro studies of lymphangiogenesis. Nat. Protoc. 12, 1077–1088 (2017).

    Article  Google Scholar 

  85. 85.

    Groom, J. R. et al. CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4(+) T helper 1 cell differentiation. Immunity 37, 1091–1103 (2012).

    Article  CAS  Google Scholar 

  86. 86.

    Malhotra, D. et al. Transcriptional profiling of steady-state and inflamed lymph node stroma reveals potential hematopoietic-stromal cross-talk pathways and suggests an active role for stroma during ongoing immune responses. J. Immunol. 188, 176.22 (2012).

    Google Scholar 

  87. 87.

    Song, J. et al. Extracellular matrix of secondary lymphoid organs impacts on B-cell fate and survival. Proc. Natl Acad. Sci. USA 110, E2915–E2924 (2013).

    Article  Google Scholar 

  88. 88.

    Cohen, J. N. et al. Tolerogenic properties of lymphatic endothelial cells are controlled by the lymph node microenvironment. PLOS ONE 9, e87740 (2014).

    Article  CAS  Google Scholar 

  89. 89.

    Kastenmuller, W. et al. Peripheral prepositioning and local CXCL9 chemokine-mediated guidance orchestrate rapid memory CD8(+) T cell responses in the lymph node. Immunity 38, 502–513 (2013).

    Article  CAS  Google Scholar 

  90. 90.

    Burrell, B. E. & Bromberg, J. S. Fates of CD4+T cells in a tolerant environment depend on timing and place of antigen exposure. Am. J. Transplant 12, 576–589 (2012).

    Article  CAS  Google Scholar 

  91. 91.

    Dubrot, J. et al. Lymph node stromal cells acquire peptide-MHCII complexes from dendritic cells and induce antigen-specific CD4(+) T cell tolerance. J. Exp. Med. 211, 1153–1166 (2014).

    Article  CAS  Google Scholar 

  92. 92.

    Hirosue, S. et al. Steady-state antigen scavenging, cross-presentation, and CD8(+) T cell priming: a new role for lymphatic endothelial cells. J. Immunol. 192, 5002–5011 (2014).

    Article  CAS  Google Scholar 

  93. 93.

    Tamburini, B. A., Burchill, M. A. & Kedl, R. M. Antigen capture and archiving by lymphatic endothelial cells following vaccination or viral infection. Nat. Commun. 5, 3989 (2014).

    Article  CAS  Google Scholar 

  94. 94.

    Warren, K. J., Iwami, D., Harris, D. G., Bromberg, J. S. & Burrell, B. E. Laminins affect T cell trafficking and allograft fate. J. Clin. Invest. 124, 2204–2218 (2014).

    Article  CAS  Google Scholar 

  95. 95.

    Astarita, J. L. et al. The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture. Nat. Immunol. 16, 75–84 (2015).

    Article  CAS  Google Scholar 

  96. 96.

    Nia, H. T. et al. Solid stress and elastic energy as measures of tumour mechanopathology. Nat. Biomed. Eng. 1, 0004 (2016).

    Article  Google Scholar 

  97. 97.

    Nolan, D. J. et al. Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev. Cell 26, 204–219 (2013).

    Article  CAS  Google Scholar 

  98. 98.

    Iftakhar-E-Khuda, I. et al. Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic. Proc. Natl Acad. Sci. USA 113, 10643–10648 (2016).

    Article  CAS  Google Scholar 

  99. 99.

    Lee, T. T. et al. Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials. Nat. Mater. 14, 352–360 (2015).

    Article  CAS  Google Scholar 

  100. 100.

    Sadtler, K. et al. Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells. Science 352, 366–370 (2016).

    Article  CAS  Google Scholar 

  101. 101.

    Doloff, J. C. et al. Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Nat. Mater. 16, 671–680 (2017).

    Article  CAS  Google Scholar 

  102. 102.

    Guc, E. et al. Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling. Biomaterials 131, 160–175 (2017).

    Article  CAS  Google Scholar 

  103. 103.

    Wang, H. M. et al. Enzyme-catalyzed formation of supramolecular hydrogels as promising vaccine adjuvants. Adv. Funct. Mater. 26, 1822–1829 (2016).

    Article  CAS  Google Scholar 

  104. 104.

    Sharp, F. A. et al. Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc. Natl Acad. Sci. USA 106, 870–875 (2009).

    Article  Google Scholar 

  105. 105.

    Andorko, J. I., Hess, K. L. & Jewell, C. M. Harnessing biomaterials to engineer the lymph node microenvironment for immunity or tolerance. Aaps J. 17, 323–338 (2015).

    Article  CAS  Google Scholar 

  106. 106.

    Hess, K. L. et al. Engineering immunological tolerance using quantum dots to tune the density of self-antigen display. Adv. Funct. Mater. 27, 1700290 (2017).

    Article  CAS  Google Scholar 

  107. 107.

    Singha, S. et al. Peptide-MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices. Nat. Nanotech. 12, 701–710 (2017).

    Article  CAS  Google Scholar 

  108. 108.

    Novkovic, M. et al. Topological small-world organization of the fibroblastic reticular cell network determines lymph node functionality. PLOS Biol. 14, e1002515 (2016).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by the United States Department of Veterans Affairs grant no. 1I01BX003690, NIH grant no. R01EB026896, NSF CAREER grant no. 1351688, the National Multiple Sclerosis Society grant no. RG-1501-02968, NIH grant no. 1R01AI062765, NIH grant no. 1R01AI114496, the Damon Runyon Foundation grant no. DRR3415, and Juvenile Diabetes Research Foundation grant no. 2-SRA-2016-319-S-B. H.B.E. is a trainee of the NIH T32 Training Program in Cell and Molecular Biology (T32GM080201). C.M.J. is a young investigator of the Alliance for Cancer Gene Therapy (grant no. 15051543) and the Melanoma Research Alliance (grant no. 348963).

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Gosselin, E.A., Eppler, H.B., Bromberg, J.S. et al. Designing natural and synthetic immune tissues. Nature Mater 17, 484–498 (2018). https://doi.org/10.1038/s41563-018-0077-6

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