Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Mimicking biological functionality with polymers for biomedical applications

Abstract

The vast opportunities for biomaterials design and functionality enabled by mimicking nature continue to stretch the limits of imagination. As both biological understanding and engineering capabilities develop, more sophisticated biomedical materials can be synthesized that have multifaceted chemical, biological and physical characteristics designed to achieve specific therapeutic goals. Mimicry is being used in the design of polymers for biomedical applications that are required locally in tissues, systemically throughout the body, and at the interface with tissues.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Strategies to create synthetic environments that mimic tissues.
Figure 2: Biomimetic polymeric nanostructures can be constructed to mimic the geometries of biological viruses for systemic delivery.
Figure 3: Biomimetic materials for the design of tissue adhesives and device coatings.
Figure 4: Synthetic polymer structures used for active interaction with immune cells.

References

  1. Rosales, A. M. & Anseth, K. S. The design of reversible hydrogels to capture extracellular matrix dynamics. Nature Rev. Mater. 1, 15012 (2016).

    Article  ADS  CAS  Google Scholar 

  2. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006). This is a landmark paper on the role of a hydrogel scaffold's mechanical properties in stem-cell differentiation.

    Article  CAS  PubMed  Google Scholar 

  3. Nelson, C. M., VanDuijn, M. M., Inman, J. L., Fletcher, D. A. & Bissell, M. J. Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science 314, 298–300 (2006).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ye, C. et al. Self-(un)rolling biopolymer microstructures: Rings, tubules, and helical tubules from the same material. Angew. Chem. Int. Edn Engl. 54, 8490–8493 (2015).

    Article  CAS  Google Scholar 

  5. Benoit, D. S. W., Schwartz, M. P., Durney, A. R. & Anseth, K. S. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nature Mater. 7, 816–823 (2008).

    Article  ADS  CAS  Google Scholar 

  6. Lin, C. C. & Anseth, K. S. Cell-cell communication mimicry with poly(ethylene glycol) hydrogels for enhancing beta-cell function. Proc. Natl Acad. Sci. USA 108, 6380–6385 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lutolf, M. P. & Hubbell, J. A. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nature Biotechnol. 23, 47–55 (2005). Pioneering study describing how synthetic hydrogels can be used to mimic the native extracellular matrix.

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  9. Martino, M. M. et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science 343, 885–888 (2014).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. DeForest, C. A. & Tirrell, D. A. A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels. Nature Mater. 14, 523–531 (2015).

    Article  ADS  CAS  Google Scholar 

  11. Chaudhuri, O. et al. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nature Mater. 15, 326–334 (2016).

    Article  ADS  CAS  Google Scholar 

  12. Dingal, P. C. D. P. et al. Fractal heterogeneity in minimal matrix models of scars modulates stiff-niche stem-cell responses via nuclear exit of a mechanorepressor. Nature Mater. 14, 951–960 (2015).

    Article  ADS  CAS  Google Scholar 

  13. Beck, J. N., Singh, A., Rothenberg, A. R., Elisseeff, J. H. & Ewald, A. J. The independent roles of mechanical, structural and adhesion characteristics of 3D hydrogels on the regulation of cancer invasion and dissemination. Biomaterials 34, 9486–9495 (2013).

    Article  CAS  PubMed  Google Scholar 

  14. Chaudhuri, O. et al. Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. Nature Mater. 13, 970–978 (2014).

    Article  ADS  CAS  Google Scholar 

  15. Johnson, R. & Halder, G. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nature Rev. Drug Discov. 13, 63–79 (2014).

    Article  CAS  Google Scholar 

  16. Sun, Y. et al. Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells. Nature Mater. 13, 599–604 (2014).

    Article  ADS  CAS  Google Scholar 

  17. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kloxin, A. M., Kasko, A. M., Salinas, C. N. & Anseth, K. S. Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324, 59–63 (2009).

  19. Gilbert, T. W., Sellaro, T. L. & Badylak, S. F. Decellularization of tissues and organs. Biomaterials 27, 3675–3683 (2006).

    CAS  PubMed  Google Scholar 

  20. Badylak, S. F. & Gilbert, T. W. Immune response to biologic scaffold materials. Semin. Immunol. 20, 109–116 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ali, O. A., Tayalia, P., Shvartsman, D., Lewin, S. & Mooney, D. J. Inflammatory cytokines presented from polymer matrices differentially generate and activate DCs. Adv. Funct. Mater. 23, 4621–4628 (2013). This is the first study to incorporate immunological cytokines into a biomaterial scaffold to modulate an immune response.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  24. Ahn, B. K., Lee, D. W., Israelachvili, J. N. & Waite, J. H. Surface-initiated self-healing of polymers in aqueous media. Nature Mater. 13, 867–872 (2014).

    Article  ADS  CAS  Google Scholar 

  25. Damo, M., Wilson, D. S., Simeoni, E. & Hubbell, J. A. TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma. Sci. Rep. 5, 17622 (2015).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  26. Veiseh, O. et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nature Mater. 14, 643–651 (2015).

    Article  ADS  CAS  Google Scholar 

  27. Leslie, D. C. et al. A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling. Nature Biotechnol. 32, 1134–1140 (2014). This paper introduces surface topographies from nature to control biomaterial surface properties.

    Article  ADS  CAS  Google Scholar 

  28. Vegas, A. J. et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nature Biotechnol. 34, 345–352 (2016). This pioneering study demonstrates that a combinatorial library approach of constructing synthetic alginate variants can lead to biomaterials that reduce foreign-body reactions in non-human primates for at least 6 months.

    Article  CAS  Google Scholar 

  29. Park, K.-C. et al. Condensation on slippery asymmetric bumps. Nature 531, 78–82 (2016).

    Article  ADS  CAS  PubMed  Google Scholar 

  30. Vegas, A. J. et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nature Med. 22, 306–311 (2016).

    Article  CAS  PubMed  Google Scholar 

  31. Singh, A. et al. Enhanced lubrication on tissue and biomaterial surfaces through peptide-mediated binding of hyaluronic acid. Nature Mater. 13, 988–995 (2014).

    Article  ADS  CAS  Google Scholar 

  32. Kelich, J. M. et al. Super-resolution imaging of nuclear import of adeno-associated virus in live cells. Mol. Ther. Meth. Clin. Dev. 2, 15047 (2015).

    Article  CAS  Google Scholar 

  33. Goldsmith, C. S. & Miller, S. E. Modern uses of electron microscopy for detection of viruses. Clin. Microbiol. Rev. 22, 552–563 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Sachse, C. et al. High-resolution electron microscopy of helical specimens: a fresh look at tobacco mosaic virus. J. Mol. Biol. 371, 812–835 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Vestergaard, G. et al. Stygiolobus rod-shaped virus and the interplay of crenarchaeal rudiviruses with the CRISPR antiviral system. J. Bacteriol. 190, 6837–6845 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bharat, T. A. et al. Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography. Proc. Natl Acad. Sci. USA 109, 4275–4280 (2012).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  37. Häring, M. et al. Virology: independent virus development outside a host. Nature 436, 1101–1102 (2005).

    Article  ADS  PubMed  CAS  Google Scholar 

  38. Jiang, X. et al. Plasmid-templated shape control of condensed DNA-block copolymer nanoparticles. Adv. Mater. 25, 227–232 (2013). This paper establishes that the shape of polymeric, plasmid DNA-containing nanoparticles can be controlled by solvent polarity, and that anisotropic biomimetic particles can have enhanced gene-delivery efficacy in vivo.

    Article  CAS  PubMed  Google Scholar 

  39. Hanson, M. C., Bershteyn, A., Crespo, M. P. & Irvine, D. J. Antigen delivery by lipid-enveloped PLGA microparticle vaccines mediated by in situ vesicle shedding. Biomacromolecules 15, 2475–2481 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Roberts, R. A. et al. Towards programming immune tolerance through geometric manipulation of phosphatidylserine. Biomaterials 72, 1–10 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Perry, J. L., Herlihy, K. P., Napier, M. E. & Desimone, J. M. PRINT: a novel platform toward shape and size specific nanoparticle theranostics. Acc. Chem. Res. 44, 990–998 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hu, C. M. et al. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc. Natl Acad. Sci. USA 108, 10980–10985 (2011). This paper uses cell membranes to camouflage and functionalize polymeric nanoparticles, opening the door to new hybrid biomimetic particles.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fang, R. H. et al. Cancer cell membrane-coated nanoparticles for anticancer vaccination and drug delivery. Nano Lett. 14, 2181–2188 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hu, C.-M. J. et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 526, 118–121 (2015).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hu, C.-M. J., Fang, R. H., Copp, J., Luk, B. T. & Zhang, L. A biomimetic nanosponge that absorbs pore-forming toxins. Nature Nanotechnol. 8, 336–340 (2013).

    Article  ADS  CAS  Google Scholar 

  46. Parodi, A. et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nature Nanotechnol. 8, 61–68 (2013); published online 16 December 2012.

    Article  ADS  CAS  Google Scholar 

  47. Xuan, M., Shao, J., Dai, L., He, Q. & Li, J. Macrophage cell membrane camouflaged mesoporous silica nanocapsules for in vivo cancer therapy. Adv. Healthcare Mater. 4, 1645–1652 (2015).

    Article  CAS  Google Scholar 

  48. Lai, P.-Y., Huang, R.-Y., Lin, S.-Y., Lin, Y.-H. & Chang, C.-W. Biomimetic stem cell membrane-camouflaged iron oxide nanoparticles for theranostic applications. RSC Adv. 5, 98222–98230 (2015).

    Article  ADS  CAS  Google Scholar 

  49. Rodriguez, P. L. et al. Minimal 'self' peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science 339, 971–975 (2013).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  50. Tsai, R. K., Rodriguez, P. L. & Discher, D. E. Self inhibition of phagocytosis: the affinity of 'marker of self' CD47 for SIRPalpha dictates potency of inhibition but only at low expression levels. Blood Cells Mol. Dis. 45, 67–74 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sosale, N. G. et al. Cell rigidity and shape override CD47's “self”-signaling in phagocytosis by hyperactivating myosin-II. Blood 125, 542–552 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wilhelm, S. et al. Analysis of nanoparticle delivery to tumours. Nature Rev. Mater. 1, 16014 (2016).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 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  PubMed  Google Scholar 

  56. Lashof-Sullivan, M. M. et al. Intravenously administered nanoparticles increase survival following blast trauma. Proc. Natl Acad. Sci. USA 111, 10293–10298 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  57. Anselmo, A. C. et al. Platelet-like nanoparticles: mimicking shape, flexibility, and surface biology of platelets to target vascular injuries. ACS Nano 8, 11243–11253 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Chan, L. W. et al. A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis. Sci. Transl. Med. 7, 277ra29 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kumar, V. A., Wickremasinghe, N. C., Shi, S. & Hartgerink, J. D. Nanofibrous snake venom hemostat. ACS Biomater. Sci. Eng. 1, 1300–1305 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lee, H., Dellatore, S. M., Miller, W. M. & Messersmith, P. B. Mussel-inspired surface chemistry for multifunctional coatings. Science 318, 426–430 (2007).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  61. Maier, G. P., Rapp, M. V., Waite, J. H., Israelachvili, J. N. & Butler, A. Adaptive synergy between catechol and lysine promotes wet adhesion by surface salt displacement. Science 349, 628–632 (2015).

    Article  ADS  CAS  PubMed  Google Scholar 

  62. Papanna, R. et al. Cryopreserved human amniotic membrane and a bioinspired underwater adhesive to seal and promote healing of iatrogenic fetal membrane defect sites. Placenta 36, 888–894 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhao, Q. et al. Underwater contact adhesion and microarchitecture in polyelectrolyte complexes actuated by solvent exchange. Nature Mater. 15, 407–412 (2016).

    Article  ADS  CAS  Google Scholar 

  64. Lee, Y. et al. Bioinspired nanoparticulate medical glues for minimally invasive tissue repair. Adv. Healthcare Mater. 4, 2587–2596 (2015).

    Article  CAS  Google Scholar 

  65. Roche, E. T. et al. A light-reflecting balloon catheter for atraumatic tissue defect repair. Sci. Transl. Med. 7, 306ra149 (2015).

    Article  PubMed  Google Scholar 

  66. Busscher, H. J. et al. Biomaterial-associated infection: Locating the finish line in the race for the surface. Sci. Transl. Med. 4, 153rv10 (2012).

    Article  PubMed  CAS  Google Scholar 

  67. Geim, A. K. et al. Microfabricated adhesive mimicking gecko foot-hair. Nature Mater. 2, 461–463 (2003).

    Article  ADS  CAS  Google Scholar 

  68. Lee, H., Lee, B. P. & Messersmith, P. B. A reversible wet/dry adhesive inspired by mussels and geckos. Nature 448, 338–341 (2007).

    Article  ADS  CAS  PubMed  Google Scholar 

  69. Mahdavi, A. et al. A biodegradable and biocompatible gecko-inspired tissue adhesive. Proc. Natl Acad. Sci. USA 105, 2307–2312 (2008).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  70. Yang, S. Y. et al. A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue. Nature Commun. 4, 1702 (2013).

    Article  ADS  CAS  Google Scholar 

  71. Chen, M., Briscoe, W. H., Armes, S. P. & Klein, J. Lubrication at physiological pressures by polyzwitterionic brushes. Science 323, 1698–1701 (2009).

    Article  ADS  CAS  PubMed  Google Scholar 

  72. Liu, G. et al. Hairy polyelectrolyte brushes-grafted thermosensitive microgels as artificial synovial fluid for simultaneous biomimetic lubrication and arthritis treatment. ACS Appl. Mater. Interfaces 6, 20452–20463 (2014).

    Article  ADS  CAS  PubMed  Google Scholar 

  73. Sicari, B. M. et al. An acellular biologic scaffold promotes skeletal muscle formation in mice and humans with volumetric muscle loss. Sci. Transl. Med. 6, 234ra58 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Beachley, V. Z. et al. Tissue matrix arrays for high-throughput screening and systems analysis of cell function. Nature Methods 12, 1197–1204 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Oliva, N. et al. Regulation of dendrimer/dextran material performance by altered tissue microenvironment in inflammation and neoplasia. Sci. Transl. Med. 7, 272ra11 (2015). This paper introduces the challenge posed by diverse physiological environments and shows they affect the responses of biomaterials in people.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Banquy, X., Burdyńska, J., Lee, D. W., Matyjaszewski, K. & Israelachvili, J. Bioinspired bottle-brush polymer exhibits low friction and amontons-like behavior. J. Am. Chem. Soc. 136, 6199–6202 (2014).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank K. Sadtler for contributions and the design of Figs 1 and 4, C. Cherry for editorial assistance, and M. Frisk for critical review and manuscript contributions. J.J.G. was supported in part by the NIH (1R01EB016721). J.H.E. was supported by the Department of Defense including the Armed Forces Institute of Regenerative Medicine.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jennifer H. Elisseeff.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Reprints and permissions information is available at www.nature.com/reprints.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Green, J., Elisseeff, J. Mimicking biological functionality with polymers for biomedical applications. Nature 540, 386–394 (2016). https://doi.org/10.1038/nature21005

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature21005

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing