Supramolecular biomaterials

Abstract

Polymers, ceramics and metals have historically dominated the application of materials in medicine. Yet rationally designed materials that exploit specific, directional, tunable and reversible non-covalent interactions offer unprecedented advantages: they enable modular and generalizable platforms with tunable mechanical, chemical and biological properties. Indeed, the reversible nature of supramolecular interactions gives rise to biomaterials that can sense and respond to physiological cues, or that mimic the structural and functional aspects of biological signalling. In this Review, we discuss the properties of several supramolecular biomaterials, as well as their applications in drug delivery, tissue engineering, regenerative medicine and immunology. We envision that supramolecular biomaterials will contribute to the development of new therapies that combine highly functional materials with unmatched patient- and application-specific tailoring of both material and biological properties.

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Figure 1: Supramolecular biomaterials are tunable, modular, responsive and biomimetic, as a result of the specific, dynamic, interchangeable and reversible motifs used in their design.
Figure 2: Supramolecular biomaterials created through the assembly of molecular stacking motifs and through engineered molecular recognition motifs for the crosslinking of polymeric precursors.
Figure 3: Modular bioactive supramolecular materials.
Figure 4: Recombinant-protein supramolecular nanostructures and hydrogels.
Figure 5: Supramolecular interactions can be harnessed to make supramolecular biomaterials with hierarchically organized structures.
Figure 6: Supramolecular materials can be used as injectable scaffolds that support the survival of therapeutic cell populations.

References

  1. 1

    Langer, R. & Tirrell, D. A. Designing materials for biology and medicine. Nature 428, 487–492 (2004).

    CAS  Article  Google Scholar 

  2. 2

    Peppas, N. A. & Langer, R. New challenges in biomaterials. Science 263, 1715–1720 (1994).

    CAS  Google Scholar 

  3. 3

    Huebsch, N. & Mooney, D. J. Inspiration and application in the evolution of biomaterials. Nature 462, 426–432 (2009).

    CAS  Article  Google Scholar 

  4. 4

    Webber, M. J., Khan, O. F., Sydlik, S. A., Tang, B. C. & Langer, R. A perspective on the clinical translation of scaffolds for tissue engineering. Annu. Biomed. Eng. 43, 641–656 (2015).

    Google Scholar 

  5. 5

    Langer, R. & Vacanti, J. P. Tissue engineering. Science 260, 920–926 (1993).

    CAS  Google Scholar 

  6. 6

    Dong, R. et al. Functional supramolecular polymers for biomedical applications. Adv. Mater. 27, 498–526 (2015).

    CAS  Google Scholar 

  7. 7

    Aida, T., Meijer, E. W. & Stupp, S. I. Functional supramolecular polymers. Science 335, 813–817 (2012).

    CAS  Article  Google Scholar 

  8. 8

    de Greef, T. F. A. et al. Supramolecular polymerization. Chem. Rev. 109, 5687–5754 (2009).

    CAS  Google Scholar 

  9. 9

    Lehn J.-M. Supramolecular chemistry — scope and perspectives. Molecules, supermolecules, and molecular devices (Nobel Lecture). Angew. Chem. Intl Ed. 27, 89–112 (1988).

    Google Scholar 

  10. 10

    Appel, E. A., del Barrio, J., Loh, X. J. & Scherman, O. A. Supramolecular polymeric hydrogels. Chem. Soc. Rev. 41, 6195–6214 (2012).

    CAS  Google Scholar 

  11. 11

    Seiffert, S. & Sprakel, J. Physical chemistry of supramolecular polymer networks. Chem. Soc. Rev. 41, 909–930 (2012).

    CAS  Google Scholar 

  12. 12

    Sijbesma, R. P. et al. Reversible polymers formed from self-complementary monomers using quadruple hydrogen bonding. Science 278, 1601–1604 (1997).

    CAS  Google Scholar 

  13. 13

    Wojtecki, R. J., Meador, M. A. & Rowan, S. J. Using the dynamic bond to access macroscopically responsive structurally dynamic polymers. Nature Mater. 10, 14–27 (2011).

    CAS  Google Scholar 

  14. 14

    Matson, J. B. & Stupp, S. I. Self-assembling peptide scaffolds for regenerative medicine. Chem. Commun. 48, 26–33 (2012).

    CAS  Google Scholar 

  15. 15

    Webber, M. J., Kessler, J. A. & Stupp, S. I. Emerging peptide nanomedicine to regenerate tissues and organs. J. Intern. Med. 267, 71–88 (2010).

    CAS  Google Scholar 

  16. 16

    Hartgerink, J. D., Beniash, E. & Stupp, S. I. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science 294, 1684–1688 (2001).

    CAS  Google Scholar 

  17. 17

    Collier, J. H. et al. Thermally and photochemically triggered self-assembly of peptide hydrogels. J. Am. Chem. Soc. 123, 9463–9464 (2001).

    CAS  Google Scholar 

  18. 18

    Aggeli, A. et al. Responsive gels formed by the spontaneous self-assembly of peptides into polymeric beta-sheet tapes. Nature 386, 259–262 (1997).

    CAS  Google Scholar 

  19. 19

    Aggeli, A. et al. Hierarchical self-assembly of chiral rod-like molecules as a model for peptide beta-sheet tapes, ribbons, fibrils, and fibers. Proc. Natl Acad. Sci. USA 98, 11857–11862 (2001).

    CAS  Google Scholar 

  20. 20

    Hauser, C. A. et al. Natural tri- to hexapeptides self-assemble in water to amyloid beta-type fiber aggregates by unexpected alpha-helical intermediate structures. Proc. Natl Acad. Sci. USA 108, 1361–1366 (2011).

    CAS  Google Scholar 

  21. 21

    Zhang, S. et al. Self-complementary oligopeptide matrices support mammalian cell attachment. Biomaterials 16, 1385–1393 (1995).

    Google Scholar 

  22. 22

    Haines-Butterick, L. et al. Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells. Proc. Natl Acad. Sci. USA 104, 7791–7796 (2007).

    CAS  Google Scholar 

  23. 23

    Schneider, J. P. et al. Responsive hydrogels from the intramolecular folding and self-assembly of a designed peptide. J. Am. Chem. Soc. 124, 15030–15037 (2002).

    CAS  Google Scholar 

  24. 24

    Berndt, P., Fields, G. B. & Tirrell, M. Synthetic lipidation of peptides and amino-acids — monolayer structure and properties. J. Am. Chem. Soc. 117, 9515–9522 (1995).

    CAS  Google Scholar 

  25. 25

    Hartgerink, J. D., Beniash, E. & Stupp, S. I. Peptide-amphiphile nanofibers: A versatile scaffold for the preparation of self-assembling materials. Proc. Natl Acad. Sci. USA 99, 5133–5138 (2002).

    CAS  Google Scholar 

  26. 26

    Webber, M. J., Berns, E. J. & Stupp, S. I. Supramolecular nanofibers of peptide amphiphiles for medicine. Isr. J. Chem. 53, 530–554 (2013).

    CAS  Google Scholar 

  27. 27

    Yang, Z. M. et al. Enzymatic formation of supramolecular hydrogels. Adv. Mater. 16, 1440–1444 (2004).

    CAS  Google Scholar 

  28. 28

    Jayawarna, V. et al. Nanostructured hydrogels for three-dimensional cell culture through self-assembly of fluorenylmethoxycarbonyl-dipeptides. Adv. Mater. 18, 611–614 (2006).

    CAS  Google Scholar 

  29. 29

    Chen, L. et al. Self-assembly mechanism for a naphthalene-dipeptide leading to hydrogelation. Langmuir 26, 5232–5242 (2010).

    CAS  Google Scholar 

  30. 30

    Fleming, S. & Ulijn, R. V. Design of nanostructures based on aromatic peptide amphiphiles. Chem. Soc. Rev. 43, 8150–8177 (2014).

    CAS  Google Scholar 

  31. 31

    Cui, H., Webber, M. J. & Stupp, S. I. Self-assembly of peptide amphiphiles: From molecules to nanostructures to biomaterials. Biopolymers 94, 1–18 (2010).

    CAS  Google Scholar 

  32. 32

    Kotch, F. W. & Raines, R. T. Self-assembly of synthetic collagen triple helices. Proc. Natl Acad. Sci. USA 103, 3028–3033 (2006).

    CAS  Google Scholar 

  33. 33

    Gauba, V. & Hartgerink, J. D. Self-assembled heterotrimeric collagen triple helices directed through electrostatic interactions. J. Am. Chem. Soc. 129, 2683–2690 (2007).

    CAS  Google Scholar 

  34. 34

    Li, Y. & Yu, S. M. Targeting and mimicking collagens via triple helical peptide assembly. Curr. Opin. Chem. Biol. 17, 968–975 (2013).

    CAS  Google Scholar 

  35. 35

    Banwell, E. F. et al. Rational design and application of responsive alpha-helical peptide hydrogels. Nature Mater. 8, 596–600 (2009).

    CAS  Google Scholar 

  36. 36

    Jing, P., Rudra, J. S., Herr, A. B. & Collier, J. H. Self-assembling peptide-polymer hydrogels designed from the coiled coil region of fibrin. Biomacromolecules 9, 2438–2446 (2008).

    CAS  Google Scholar 

  37. 37

    Gradisar, H. et al. Design of a single-chain polypeptide tetrahedron assembled from coiled-coil segments. Nature Chem. Biol. 9, 362–366 (2013).

    CAS  Google Scholar 

  38. 38

    Fletcher, J. M. et al. Self-assembling cages from coiled-coil peptide modules. Science 340, 595–599 (2013).

    CAS  Google Scholar 

  39. 39

    Ryadnov, M. G. & Woolfson, D. N. Engineering the morphology of a self-assembling protein fibre. Nature Mater. 2, 329–332 (2003).

    CAS  Google Scholar 

  40. 40

    Petka, W. A., Harden, J. L., McGrath, K. P., Wirtz, D. & Tirrell, D. A. Reversible hydrogels from self-assembling artificial proteins. Science 281, 389–392 (1998).

    CAS  Google Scholar 

  41. 41

    Shen, W., Zhang, K., Kornfield, J. A. & Tirrell, D. A. Tuning the erosion rate of artificial protein hydrogels through control of network topology. Nature Mater. 5, 153–158 (2006).

    CAS  Google Scholar 

  42. 42

    Lu, H. D., Charati, M. B., Kim, I. L. & Burdick, J. A. Injectable shear-thinning hydrogels engineered with a self-assembling dock-and-lock mechanism. Biomaterials 33, 2145–2153 (2012).

    CAS  Google Scholar 

  43. 43

    Wong Po Foo, C. T. S., Lee, J. S., Mulyasasmita, W., Parisi-Amon, A. & Heilshorn, S. C. Two-component protein-engineered physical hydrogels for cell encapsulation. Proc. Natl Acad. Sci. USA 106, 22067–22072 (2009).

    Google Scholar 

  44. 44

    Davis, M. E. & Brewster, M. E. Cyclodextrin-based pharmaceutics: Past, present and future. Nature Rev. Drug Discov. 3, 1023–1035 (2004).

    CAS  Google Scholar 

  45. 45

    Rodell, C. B., Kaminski, A. & Burdick, J. A. Rational design of network properties in guest–host assembled and shear-thinning hyaluronic acid hydrogels. Biomacromolecules 14, 4125–4134 (2013).

    CAS  Google Scholar 

  46. 46

    Kakuta, T. et al. Preorganized hydrogel: Self-healing properties of supramolecular hydrogels formed by polymerization of host–guest-monomers that contain cyclodextrins and hydrophobic guest groups. Adv. Mater. 25, 2849–2853 (2013).

    CAS  Google Scholar 

  47. 47

    Park, K. M. et al. In situ supramolecular assembly and modular modification of hyaluronic acid hydrogels for 3D cellular engineering. ACS Nano 6, 2960–2968 (2012).

    CAS  Google Scholar 

  48. 48

    Davis, M. E. Design and development of IT-101, a cyclodextrin-containing polymer conjugate of camptothecin. Adv. Drug Deliver. Rev. 61, 1189–1192 (2009).

    CAS  Google Scholar 

  49. 49

    Harada, A., Kobayashi, R., Takashima, Y., Hashidzume, A. & Yamaguchi, H. Macroscopic self-assembly through molecular recognition. Nature Chem. 3, 34–37 (2010).

    Google Scholar 

  50. 50

    Yamaguchi, H. et al. Photoswitchable gel assembly based on molecular recognition. Nature Commun. 3, 603 (2012).

    Google Scholar 

  51. 51

    Boekhoven, J., Perez, C. M. R., Sur, S., Worthy, A. & Stupp, S. I. Dynamic display of bioactivity through host–guest chemistry. Angew. Chem. Intl Ed. 52, 12077–12080 (2013).

    CAS  Google Scholar 

  52. 52

    Bartlett, D. W., Su, H., Hildebrandt, I. J., Weber, W. A. & Davis, M. E. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc. Natl Acad. Sci. USA 104, 15549–15554 (2007).

    CAS  Google Scholar 

  53. 53

    Jung, H. et al. 3D tissue engineered supramolecular hydrogels for controlled chondrogenesis of human mesenchymal stem cells. Biomacromolecules 15, 707–714 (2014).

    CAS  Google Scholar 

  54. 54

    Yeom, J. et al. Supramolecular hydrogels for long-term bioengineered stem cell therapy. Adv. Health. Mater. 4, 237–244 (2015).

    CAS  Google Scholar 

  55. 55

    Appel, E. A. et al. Supramolecular cross-linked networks via host–guest complexation with cucurbit[8]uril. J. Am. Chem. Soc. 132, 14251–14260 (2010).

    CAS  Google Scholar 

  56. 56

    Appel, E. A., Forster, R. A., Koutsioubas, A., Toprakcioglu, C. & Scherman, O. A. Activation energies control macroscopic properties of physically crosslinked materials. Angew. Chem. Intl Ed. 53, 10038–10043 (2014).

    CAS  Google Scholar 

  57. 57

    Appel, E. A. et al. High-water-content hydrogels from renewable resources through host–guest interactions. J. Am. Chem. Soc. 134, 11767–11773 (2012).

    CAS  Google Scholar 

  58. 58

    Dankers, P. Y. W., Harmsen, M. C., Brouwer, L. A., Van Luyn, M. J. A. & Meijer, E. W. A modular and supramolecular approach to bioactive scaffolds for tissue engineering. Nature Mater. 4, 568–574 (2005).

    CAS  Google Scholar 

  59. 59

    Dankers, P. Y. W. et al. Hierarchical formation of supramolecular transient networks in water: A modular injectable delivery system. Adv. Mater. 24, 2703–2709 (2012).

    CAS  Google Scholar 

  60. 60

    Wisse, E. et al. Multicomponent supramolecular thermoplastic elastomer with peptide-modified nanofibers. J. Polym. Sci. Pol. Chem. 49, 1764–1771 (2011).

    CAS  Google Scholar 

  61. 61

    Fukushima, K. et al. Supramolecular high-aspect ratio assemblies with strong antifungal activity. Nature Commun. 4, 2861 (2013).

    Google Scholar 

  62. 62

    Fukushima, K. et al. Broad-spectrum antimicrobial supramolecular assemblies with distinctive size and shape. ACS Nano 6, 9191–9199 (2012).

    CAS  Google Scholar 

  63. 63

    Kim, S. H. et al. A supramolecularly assisted transformation of block-copolymer micelles into nanotubes. Angew. Chem. Intl Ed. 48, 4508–4512 (2009).

    CAS  Google Scholar 

  64. 64

    Leenders, C. M. A. et al. From supramolecular polymers to hydrogel materials. Mater. Horiz. 1, 116–120 (2014).

    CAS  Google Scholar 

  65. 65

    Roosma, J., Mes, T., Leclere, P., Palmans, A. R. A. & Meijer, E. W. Supramolecular materials from benzene-1,3,5-tricarboxamide-based nanorods. J. Am. Chem. Soc. 130, 1120–1121 (2008).

    CAS  Google Scholar 

  66. 66

    Buerkle, L. E., von Recum, H. A. & Rowan, S. J. Toward potential supramolecular tissue engineering scaffolds based on guanosine derivatives. Chem. Sci. 3, 564–572 (2012).

    CAS  Google Scholar 

  67. 67

    Seeman, N. C. DNA in a material world. Nature 421, 427–431 (2003).

    Google Scholar 

  68. 68

    Stephanopoulos, N. et al. Bioactive DNA-peptide nanotubes enhance the differentiation of neural stem cells into neurons. Nano Lett. 15, 603–609 (2015).

    CAS  Google Scholar 

  69. 69

    Fullenkamp, D. E., He, L., Barrett, D. G., Burghardt, W. R. & Messersmith, P. B. Mussel-inspired histidine-based transient network metal coordination hydrogels. Macromolecules 46, 1167–1174 (2013).

    CAS  Google Scholar 

  70. 70

    Holten-Andersen, N. et al. pH-induced metal-ligand cross-links inspired by mussel yield self-healing polymer networks with near-covalent elastic moduli. Proc. Natl Acad. Sci. USA 108, 2651–2655 (2011).

    CAS  Google Scholar 

  71. 71

    Mozhdehi, D., Ayala, S., Cromwell, O. R. & Guan, Z. Self-healing multiphase polymers via dynamic metal–ligand interactions. J. Am. Chem. Soc. 136, 16128–16131 (2014).

    CAS  Google Scholar 

  72. 72

    Beck, J. B. & Rowan, S. J. Multistimuli, multiresponsive metallo-supramolecular polymers. J. Am. Chem. Soc. 125, 13922–13923 (2003).

    CAS  Google Scholar 

  73. 73

    Burnworth, M. et al. Optically healable supramolecular polymers. Nature 472, 334–337 (2011).

    CAS  Google Scholar 

  74. 74

    Davis, M. E. The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: From concept to clinic. Mol. Pharm. 6, 659–668 (2009).

    CAS  Google Scholar 

  75. 75

    Davis, M. E. et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464, 1067–1070 (2010).

    CAS  Google Scholar 

  76. 76

    An, Q. et al. A Supramolecular system for the electrochemically controlled release of cells. Angew. Chem. Intl Ed. 51, 12233–12237 (2012).

    CAS  Google Scholar 

  77. 77

    Hudalla, G. A. et al. Gradated assembly of multiple proteins into supramolecular nanomaterials. Nature Mater. 13, 829–836 (2014).

    CAS  Google Scholar 

  78. 78

    Capito, R. M., Azevedo, H. S., Velichko, Y. S., Mata, A. & Stupp, S. I. Self-assembly of large and small molecules into hierarchically ordered sacs and membranes. Science 319, 1812–1816 (2008).

    CAS  Google Scholar 

  79. 79

    Guo, M. Y., Cao, X. Y., Meijer, E. W. & Dankers, P. Y. W. Core–shell capsules based on supramolecular hydrogels show shell-related erosion and release due to confinement. Macromol. Biosci. 13, 77–83 (2013).

    CAS  Google Scholar 

  80. 80

    Mollet, B. B. et al. A modular approach to easily processable supramolecular bilayered scaffolds with tailorable properties. J. Mater. Chem. B 2, 2483–2493 (2014).

    CAS  Google Scholar 

  81. 81

    Zhang, J. et al. One-step fabrication of supramolecular microcapsules from microfluidic droplets. Science 335, 690–694 (2012).

    CAS  Google Scholar 

  82. 82

    Sur, S., Matson, J. B., Webber, M. J., Newcomb, C. J. & Stupp, S. I. Photodynamic control of bioactivity in a nanofiber matrix. ACS Nano 6, 10776–10785 (2012).

    CAS  Google Scholar 

  83. 83

    Rubinstein, M. & Colby, R. H. Polymer Physics (Oxford Univ. Press, 2003).

    Google Scholar 

  84. 84

    Yount, W., Loveless, D. & Craig, S. Small-molecule dynamics and mechanisms underlying the macroscopic mechanical properties of coordinatively cross-linked polymer networks. J. Am. Chem. Soc. 127, 14488–14496 (2005).

    CAS  Google Scholar 

  85. 85

    Yount, W., Loveless, D. & Craig, S. Strong means slow: Dynamic contributions to the bulk mechanical properties of supramolecular networks. Angew. Chem. Intl Ed. 44, 2746–2748 (2005).

    CAS  Google Scholar 

  86. 86

    Bastings, M. M. C. et al. A fast pH-switchable and self-healing supramolecular hydrogel carrier for guided, local catheter injection in the infarcted myocardium. Adv. Health. Mater 3, 70–78 (2014).

    CAS  Google Scholar 

  87. 87

    Pashuck, E. T., Cui, H. & Stupp, S. I. Tuning supramolecular rigidity of peptide fibers through molecular structure. J. Am. Chem. Soc. 132, 6041–6046 (2010).

    CAS  Google Scholar 

  88. 88

    Mulyasasmita, W., Lee, J. S. & Heilshorn, S. C. Molecular-level engineering of protein physical hydrogels for predictive sol-gel phase behavior. Biomacromolecules 12, 3406–3411 (2011).

    CAS  Google Scholar 

  89. 89

    Appel, E. A., Forster, R. A., Rowland, M. J. & Scherman, O. A. The control of cargo release from physically crosslinked hydrogels by crosslink dynamics. Biomaterials 35, 9897–9903 (2014).

    CAS  Google Scholar 

  90. 90

    Aguado, B. A., Mulyasasmita, W., Su, J., Lampe, K. J. & Heilshorn, S. C. Improving viability of stem cells during syringe needle flow through the design of hydrogel cell carriers. Tissue Eng. Pt A 18, 806–815 (2012).

    CAS  Google Scholar 

  91. 91

    Newcomb, C. J. et al. Cell death versus cell survival instructed by supramolecular cohesion of nanostructures. Nature Commun. 5, 3321 (2014).

    Google Scholar 

  92. 92

    Zhang, S. et al. A self-assembly pathway to aligned monodomain gels. Nature Mater. 9, 594–601 (2010).

    CAS  Google Scholar 

  93. 93

    Cui, H. et al. Spontaneous and X-ray-triggered crystallization at long range in self-assembling filament networks. Science 327, 555–559 (2010).

    CAS  Google Scholar 

  94. 94

    Lu, H. D., Soranno, D. E., Rodell, C. B., Kim, I. L. & Burdick, J. A. Secondary photocrosslinking of injectable shear-thinning dock-and-lock hydrogels. Adv. Health. Mater. 2, 1028–1036 (2013).

    CAS  Google Scholar 

  95. 95

    Hsu, L., Cvetanovich, G. L. & Stupp, S. I. Peptide amphiphile nanofibers with conjugated polydiacetylene backbones in their core. J. Am. Chem. Soc. 130, 3892–3899 (2008).

    CAS  Google Scholar 

  96. 96

    Webber, M. J., Newcomb, C. J., Bitton, R. & Stupp, S. I. Switching of self-assembly in a peptide nanostructure with a specific enzyme. Soft Matter 7, 9665–9672 (2011).

    CAS  Google Scholar 

  97. 97

    Yang, Z., Liang, G., Wang, L. & Xu, B. Using a kinase/phosphatase switch to regulate a supramolecular hydrogel and forming the supramolecular hydrogel in vivo. J. Am. Chem. Soc. 128, 3038–3043 (2006).

    CAS  Google Scholar 

  98. 98

    Williams, R. J. et al. Enzyme-assisted self-assembly under thermodynamic control. Nature Nanotechnol. 4, 19–24 (2009).

    CAS  Google Scholar 

  99. 99

    Jun, H. W., Yuwono, V., Paramonov, S. E. & Hartgerink, J. D. Enzyme-mediated degradation of peptide-amphiphile nanofiber networks. Adv. Mater. 17, 2612–2617 (2005).

    CAS  Google Scholar 

  100. 100

    Toledano, S., Williams, R. J., Jayawarna, V. & Ulijn, R. V. Enzyme-triggered self-assembly of peptide hydrogels via reversed hydrolysis. J. Am. Chem. Soc. 128, 1070–1071 (2006).

    CAS  Google Scholar 

  101. 101

    Lin, Y. A., Ou, Y. C., Cheetham, A. G. & Cui, H. Rational design of MMP degradable peptide-based supramolecular filaments. Biomacromolecules 15, 1419–1427 (2014).

    CAS  Google Scholar 

  102. 102

    Pappas, C. G., Sasselli, I. R. & Ulijn, R. V. Biocatalytic pathway selection in transient tripeptide nanostructures. Angew. Chem. Intl Ed. 54, 8119–8123 (2015).

    CAS  Google Scholar 

  103. 103

    Pires, R. A. et al. Controlling cancer cell fate using localized biocatalytic self-assembly of an aromatic carbohydrate amphiphile. J. Am. Chem. Soc. 137, 576–579 (2015).

    CAS  Google Scholar 

  104. 104

    Frederix, P. W. et al. Exploring the sequence space for (tri-)peptide self-assembly to design and discover new hydrogels. Nature Chem. 7, 30–37 (2015).

    CAS  Google Scholar 

  105. 105

    Morris, K. L. et al. Chemically programmed self-sorting of gelator networks. Nature Commun. 4, 1480 (2014).

    Google Scholar 

  106. 106

    Albertazzi, L. et al. Spatiotemporal control and superselectivity in supramolecular polymers using multivalency. Proc. Natl Acad. Sci. USA 110, 12203–12208 (2013).

    CAS  Google Scholar 

  107. 107

    Silva, G. A. et al. Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science 303, 1352–1355 (2004).

    CAS  Google Scholar 

  108. 108

    Storrie, H. et al. Supramolecular crafting of cell adhesion. Biomaterials 28, 4608–4618 (2007).

    CAS  Google Scholar 

  109. 109

    Webber, M. J. et al. Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair. Proc. Natl Acad. Sci. USA 108, 13438–13443 (2011).

    CAS  Google Scholar 

  110. 110

    Liu, J. C., Heilshorn, S. C. & Tirrell, D. A. Comparative cell response to artificial extracellular matrix proteins containing the RGD and CS5 cell-binding domains. Biomacromolecules 5, 497–504 (2004).

    CAS  Google Scholar 

  111. 111

    Heilshorn, S. C., DiZio, K. A., Welsh, E. R. & Tirrell, D. A. Endothelial cell adhesion to the fibronectin CS5 domain in artificial extracellular matrix proteins. Biomaterials 24, 4245–4252 (2003).

    CAS  Google Scholar 

  112. 112

    Panitch, A., Yamaoka, T., Fournier, M. J., Mason, T. L. & Tirrell, D. A. Design and biosynthesis of elastin-like artificial extracellular matrix proteins containing periodically spaced fibronectin CS5 domains. Macromolecules 32, 1701–1703 (1999).

    CAS  Google Scholar 

  113. 113

    Webber, M. J., Matson, J. B., Tamboli, V. K. & Stupp, S. I. Controlled release of dexamethasone from peptide nanofiber gels to modulate inflammatory response. Biomaterials 33, 6823–6832 (2012).

    CAS  Google Scholar 

  114. 114

    Zhang, P., Cheetham, A. G., Lin, Y. A. & Cui, H. Self-assembled Tat nanofibers as effective drug carrier and transporter. ACS Nano 7, 5965–5977 (2013).

    CAS  Google Scholar 

  115. 115

    Appel, E. A., Loh, X. J., Jones, S. T., Dreiss, C. A. & Scherman, O. A. Sustained release of proteins from high water content supramolecular hydrogels. Biomaterials 33, 4646–4652 (2012).

    CAS  Google Scholar 

  116. 116

    Cheetham, A. G., Ou, Y. C., Zhang, P. & Cui, H. Linker-determined drug release mechanism of free camptothecin from self-assembling drug amphiphiles. Chem. Commun. 50, 6039–6042 (2014).

    CAS  Google Scholar 

  117. 117

    Mulyasasmita, W., Cai, L., Hori, Y. & Heilshorn, S. C. Avidity-controlled delivery of angiogenic peptides from injectable molecular-recognition hydrogels. Tissue Eng. Pt A 20, 2102–2114 (2014).

    CAS  Google Scholar 

  118. 118

    Rajangam, K. et al. Heparin binding nanostructures to promote growth of blood vessels. Nano Lett. 6, 2086–2090 (2006).

    CAS  Google Scholar 

  119. 119

    Lee, S. S. et al. Gel scaffolds of BMP-2-binding peptide amphiphile nanofibers for spinal arthrodesis. Adv. Health. Mater. 4, 131–141 (2015).

    CAS  Google Scholar 

  120. 120

    Wang, L., Li, L. L., Fan, Y. S. & Wang, H. Host-guest supramolecular nanosystems for cancer diagnostics and therapeutics. Adv. Mater. 25, 3888–3898 (2013).

    CAS  Google Scholar 

  121. 121

    Altunbas, A., Lee, S. J., Rajasekaran, S. A., Schneider, J. P. & Pochan, D. J. Encapsulation of curcumin in self-assembling peptide hydrogels as injectable drug delivery vehicles. Biomaterials 32, 5906–5914 (2011).

    CAS  Google Scholar 

  122. 122

    Soukasene, S. et al. Antitumor activity of peptide amphiphile nanofiber-encapsulated camptothecin. ACS Nano 5, 9113–9121 (2011).

    CAS  Google Scholar 

  123. 123

    Standley, S. M. et al. Induction of cancer cell death by self-assembling nanostructures incorporating a cytotoxic peptide. Cancer Res. 70, 3020–3026 (2010).

    CAS  Google Scholar 

  124. 124

    Toft, D. J. et al. Coassembled cytotoxic and pegylated peptide amphiphiles form filamentous nanostructures with potent antitumor activity in models of breast cancer. ACS Nano 6, 7956–7965 (2012).

    CAS  Google Scholar 

  125. 125

    Zhou, J. & Xu, B. Enzyme-instructed self-assembly: A multistep process for potential cancer therapy. Bioconjug. Chem. 26, 987–999 (2015).

    CAS  Google Scholar 

  126. 126

    Kalafatovic, D. et al. MMP-9 triggered micelle-to-fibre transitions for slow release of doxorubicin. Biomater. Sci. 3, 246–249 (2015).

    CAS  Google Scholar 

  127. 127

    Bremmer, S. C., McNeil, A. J. & Soellner, M. B. Enzyme-triggered gelation: Targeting proteases with internal cleavage sites. Chem. Commun. 50, 1691–1693 (2014).

    CAS  Google Scholar 

  128. 128

    Zhou, J., Du, X. & Xu, B. Prion-like nanofibrils of small molecules (PriSM): A new frontier at the intersection of supramolecular chemistry and cell biology. Prion 9, 110–118 (2015).

    CAS  Google Scholar 

  129. 129

    Kuang, Y. et al. Prion-like nanofibrils of small molecules (PriSM) selectively inhibit cancer cells by impeding cytoskeleton dynamics. J. Biol. Chem. 289, 29208–29218 (2014).

    CAS  Google Scholar 

  130. 130

    Kuang, Y., Du, X., Zhou, J. & Xu, B. Supramolecular nanofibrils inhibit cancer progression in vitro and in vivo. Adv. Health. Mater. 3, 1217–1221 (2014).

    CAS  Google Scholar 

  131. 131

    Davis, M. E. et al. Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation 111, 442–450 (2005).

    CAS  Google Scholar 

  132. 132

    Mulyasasmita, W. et al. Avidity-controlled hydrogels for injectable co-delivery of induced pluripotent stem cell-derived endothelial cells and growth factors. J. Control. Release 191, 71–81 (2014).

    CAS  Google Scholar 

  133. 133

    Parisi-Amon, A., Mulyasasmita, W., Chung, C. & Heilshorn, S. C. Protein-engineered injectable hydrogel to improve retention of transplanted adipose-derived stem cells. Adv. Health. Mater. 2, 428–432 (2013).

    CAS  Google Scholar 

  134. 134

    Webber, M. J. et al. Development of bioactive peptide amphiphiles for therapeutic cell delivery. Acta Biomater. 6, 3–11 (2010).

    CAS  Google Scholar 

  135. 135

    Greenwood-Goodwin, M., Teasley, E. S. & Heilshorn, S. C. Dual-stage growth factor release within 3D protein-engineered hydrogel niches promotes adipogenesis. Biomater. Sci. 2, 1627–1639 (2014).

    CAS  Google Scholar 

  136. 136

    Du, X. et al. Supramolecular assemblies of a conjugate of nucleobase, amino acids, and saccharide act as agonists for proliferation of embryonic stem cells and development of zygotes. Bioconjug. Chem. 25, 1031–1035 (2014).

    CAS  Google Scholar 

  137. 137

    Berns, E. J. et al. Aligned neurite outgrowth and directed cell migration in self-assembled monodomain gels. Biomaterials 35, 185–195 (2014).

    CAS  Google Scholar 

  138. 138

    Ellis-Behnke, R. G. et al. Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. Proc. Natl Acad. Sci. USA 103, 5054–5059 (2006).

    CAS  Google Scholar 

  139. 139

    Tysseling-Mattiace, V. M. et al. Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury. J. Neurosci. 28, 3814–3823 (2008).

    CAS  Google Scholar 

  140. 140

    Huang, Z., Newcomb, C. J., Bringas, P. Jr, Stupp, S. I. & Snead, M. L. Biological synthesis of tooth enamel instructed by an artificial matrix. Biomaterials 31, 9202–9211 (2010).

    CAS  Google Scholar 

  141. 141

    Galler, K. M., Hartgerink, J. D., Cavender, A. C., Schmalz, G. & D'Souza, R. N. A customized self-assembling peptide hydrogel for dental pulp tissue engineering. Tissue Eng. Pt A 18, 176–184 (2012).

    CAS  Google Scholar 

  142. 142

    Koudstaal, S. et al. Sustained delivery of insulin-like growth factor-1/hepatocyte growth factor stimulates endogenous cardiac repair in the chronic infarcted pig heart. J. Cardiovasc. Transl. 7, 232–241 (2014).

    Google Scholar 

  143. 143

    Webber, M. J. et al. Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases. J. Tissue Eng. Regen. M. 4, 600–610 (2010).

    CAS  Google Scholar 

  144. 144

    Lee, S. S. et al. Bone regeneration with low dose BMP-2 amplified by biomimetic supramolecular nanofibers within collagen scaffolds. Biomaterials 34, 452–459 (2013).

    CAS  Google Scholar 

  145. 145

    Shah, R. N. et al. Supramolecular design of self-assembling nanofibers for cartilage regeneration. Proc. Natl Acad. Sci. USA 107, 3293–3298 (2010).

    CAS  Google Scholar 

  146. 146

    Soranno, D. E., Lu, H. D., Weber, H. M., Rai, R. & Burdick, J. A. Immunotherapy with injectable hydrogels to treat obstructive nephropathy. J. Biomed. Mater. Res. A 102, 2173–2180 (2014).

    Google Scholar 

  147. 147

    Dankers, P. Y. W. et al. Development and in-vivo characterization of supramolecular hydrogels for intrarenal drug delivery. Biomaterials 33, 5144–5155 (2012).

    CAS  Google Scholar 

  148. 148

    Padin-Iruegas, M. E. et al. Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction. Circulation 120, 876–887 (2009).

    CAS  Google Scholar 

  149. 149

    Tongers, J. et al. Enhanced potency of cell-based therapy for ischemic tissue repair using an injectable bioactive epitope presenting nanofiber support matrix. J. Mol. Cell. Cardiol. 74, 231–239 (2014).

    CAS  Google Scholar 

  150. 150

    Dankers, P. Y. et al. Bioengineering of living renal membranes consisting of hierarchical, bioactive supramolecular meshes and human tubular cells. Biomaterials 32, 723–733 (2011).

    CAS  Google Scholar 

  151. 151

    Angeloni, N. L. et al. Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers. Biomaterials 32, 1091–1101 (2011).

    CAS  Google Scholar 

  152. 152

    Lehn, J. M. Perspectives in chemistry — aspects of adaptive chemistry and materials. Angew. Chem. Intl Ed. 54, 3276–3289 (2015).

    CAS  Google Scholar 

  153. 153

    Hou, S., Wang, X., Park, S., Jin, X. & Ma, P. X. Rapid self-integrating, injectable hydrogel for tissue complex regeneration. Adv. Health. Mater. 4, 1491–1495 (2015).

    CAS  Google Scholar 

  154. 154

    Rudra, J. S. et al. Modulating adaptive immune responses to peptide self-assemblies. ACS Nano 6, 1557–1564 (2012).

    CAS  Google Scholar 

  155. 155

    Rudra, J. S., Tian, Y. F., Jung, J. P. & Collier, J. H. A self-assembling peptide acting as an immune adjuvant. Proc. Natl Acad. Sci. USA 107, 622–627 (2010).

    CAS  Google Scholar 

  156. 156

    Black, M. et al. Self-assembled peptide amphiphile micelles containing a cytotoxic T-cell epitope promote a protective immune response in vivo. Adv. Mater. 24, 3845–3849 (2012).

    CAS  Google Scholar 

  157. 157

    Hudalla, G. A. et al. A self-adjuvanting supramolecular vaccine carrying a folded protein antigen. Adv. Health. Mater. 2, 1114–1119 (2013).

    CAS  Google Scholar 

  158. 158

    Ingber, D. E. Mechanobiology and diseases of mechanotransduction. Annu. Med. 35, 564–577 (2003).

    Google Scholar 

  159. 159

    Xu, J. et al. Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo. J. Cell Biol. 154, 1069–1079 (2001).

    CAS  Google Scholar 

  160. 160

    Ghanaati, S. et al. Dynamic in vivo biocompatibility of angiogenic peptide amphiphile nanofibers. Biomaterials 30, 6202–6212 (2009).

    CAS  Google Scholar 

  161. 161

    Geng, Y. et al. Shape effects of filaments versus spherical particles in flow and drug delivery. Nature Nanotechnol. 2, 249–255 (2007).

    CAS  Google Scholar 

  162. 162

    Pal, A. et al. Controlling the structure and length of self-synthesizing supramolecular polymers through nucleated growth and disassembly. Angew. Chem. Intl Ed. 54, 7852–7856 (2015).

    CAS  Google Scholar 

  163. 163

    Ruff, Y., Moyer, T., Newcomb, C. J., Demeler, B. & Stupp, S. I. Precision templating with DNA of a virus-like particle with peptide nanostructures. J. Am. Chem. Soc. 135, 6211–6219 (2013).

    CAS  Google Scholar 

  164. 164

    Chan, I. S. & Ginsburg, G. S. Personalized medicine: Progress and promise. Annu. Rev. Genom. Hum. Genet. 12, 217–244 (2011).

    CAS  Google Scholar 

  165. 165

    de Boer, J. & van Blitterswijk, C. A. Materiomics: High Throughput Screening of Biomaterial Properties (Cambridge Univ. Press, 2013).

    Google Scholar 

  166. 166

    Collier, J. H. & Segura, T. Evolving the use of peptides as components of biomaterials. Biomaterials 32, 4198–4204 (2011).

    CAS  Google Scholar 

  167. 167

    Appel, E. A. et al. Self-assembled hydrogels utilizing polymer-nanoparticle interactions. Nature Commun. 6, 6295 (2015).

    CAS  Google Scholar 

  168. 168

    Pashuck, E. T. & Stevens, M. M. Designing regenerative biomaterial therapies for the clinic. Sci. Transl. Med. 4, 160sr4 (2012).

    Google Scholar 

  169. 169

    Prestwich, G. D. et al. What is the greatest regulatory challenge in the translation of biomaterials to the clinic? Sci. Transl. Med. 4, 160cm14 (2012).

    Google Scholar 

  170. 170

    Zhou, M. et al. Self-assembled peptide-based hydrogels as scaffolds for anchorage-dependent cells. Biomaterials 30, 2523–2530 (2009).

    CAS  Google Scholar 

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Acknowledgements

M.J.W. acknowledges support from the National Institutes of Health (NIDDK) through a Ruth L. Kirschstein National Research Service Award (F32DK101335). E.A.A. acknowledges support from a Wellcome Trust–MIT postdoctoral fellowship.

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Webber, M., Appel, E., Meijer, E. et al. Supramolecular biomaterials. Nature Mater 15, 13–26 (2016). https://doi.org/10.1038/nmat4474

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