Perspective

Leveraging advances in biology to design biomaterials

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Abstract

Biomaterials have dramatically increased in functionality and complexity, allowing unprecedented control over the cells that interact with them. From these engineering advances arises the prospect of improved biomaterial-based therapies, yet practical constraints favour simplicity. Tools from the biology community are enabling high-resolution and high-throughput bioassays that, if incorporated into a biomaterial design framework, could help achieve unprecedented functionality while minimizing the complexity of designs by identifying the most important material parameters and biological outputs. However, to avoid data explosions and to effectively match the information content of an assay with the goal of the experiment, material screens and bioassays must be arranged in specific ways. By borrowing methods to design experiments and workflows from the bioprocess engineering community, we outline a framework for the incorporation of next-generation bioassays into biomaterials design to effectively optimize function while minimizing complexity. This framework can inspire biomaterials designs that maximize functionality and translatability.

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References

  1. 1.

    et al. Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage. Nat. Mater. 15, 477–484 (2016).

  2. 2.

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

  3. 3.

    et al. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat. Mater. 15, 669–678 (2016).

  4. 4.

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

  5. 5.

    et al. Combinatorial discovery of polymers resistant to bacterial attachment. Nat. Biotechnol. 30, 868–875 (2012).

  6. 6.

    , , , & Infection-mimicking materials to program dendritic cells in situ. Nat. Mater. 8, 151–158 (2009).

  7. 7.

    & Controlled architecture for improved macromolecular memory within polymer networks. Curr. Opin. Biotechnol. 40, 170–176 (2016).

  8. 8.

    , , & Programming molecular association and viscoelastic behavior in protein networks. Adv. Mater. 28, 4651–4657 (2016).

  9. 9.

    , , , & Click hydrogels, microgels and nanogels: emerging platforms for drug delivery and tissue engineering. Biomaterials 35, 4969–4985 (2014).

  10. 10.

    & Engineered hydrogels for local and sustained delivery of RNA-interference therapies. Adv. Healthc. Mater. 6, 1601041 (2017).

  11. 11.

    et al. Functional immobilization of signaling proteins enables control of stem cell fate. Nat. Methods 5, 645–650 (2008).

  12. 12.

    & A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels. Nat. Mater. 14, 523–531 (2015).

  13. 13.

    RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol. 12, 697–715 (1996).

  14. 14.

    , , & Engineering growth factors for regenerative medicine applications. Acta Biomater. 30, 1–12 (2016).

  15. 15.

    , , & Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

  16. 16.

    et al. N-cadherin adhesive interactions modulate matrix mechanosensing and fate commitment of mesenchymal stem cells. Nat. Mater. 15, 1297–1306 (2016).

  17. 17.

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

  18. 18.

    et al. Fibrous nonlinear elasticity enables positive mechanical feedback between cells and ECMs. Proc. Natl Acad. Sci. USA 113, 14043–14048 (2016).

  19. 19.

    , & Harnessing nanotopography and integrin-matrix interactions to influence stem cell fate. Nat. Mater. 13, 558–569 (2014).

  20. 20.

    et al. Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. Mol. Biol. Cell 11, 1047–1060 (2000).

  21. 21.

    et al. Biophysical regulation of epigenetic state and cell reprogramming. Nat. Mater. 12, 1154–1162 (2013).

  22. 22.

    , , & Effect of surface roughness of hydroxyapatite on human bone marrow cell adhesion, proliferation, differentiation and detachment strength. Biomaterials 22, 87–96 (2000).

  23. 23.

    et al. Controlling the porosity and microarchitecture of hydrogels for tissue engineering. Tissue Eng. Part B Rev. 16, 371–383 (2010).

  24. 24.

    et al. Injectable cryogel-based whole-cell cancer vaccines. Nat. Commun. 6, 7556 (2015).

  25. 25.

    , , , & Biopolymers and supramolecular polymers as biomaterials for biomedical applications. MRS Bull. 40, 1089–1101 (2015).

  26. 26.

    , , & Three-dimensional bioprinting of thick vascularized tissues. Proc. Natl Acad. Sci. USA 113, 3179–3184 (2016).

  27. 27.

    & Cell sensing of physical properties at the nanoscale: mechanisms and control of cell adhesion and phenotype. Acta Biomater. 30, 26–48 (2016).

  28. 28.

    & Design properties of hydrogel tissue-engineering scaffolds. Expert Rev. Med. Devices 8, 607–626 (2011).

  29. 29.

    & A photolabile hydrogel for guided three-dimensional cell growth and migration. Nat. Mater. 3, 249–253 (2004).

  30. 30.

    et al. In situ cell manipulation through enzymatic hydrogel photopatterning. Nat. Mater. 12, 1072–1078 (2013).

  31. 31.

    , , & Mechanical memory and dosing influence stem cell fate. Nat. Mater. 13, 645–652 (2014).

  32. 32.

    & Dynamic microenvironments: the fourth dimension. Sci. Transl. Med. 4, 160ps124 (2012).

  33. 33.

    et al. Directing cell migration and organization via nanocrater-patterned cell-repellent interfaces. Nat. Mater. 14, 918–923 (2015).

  34. 34.

    , , & Biomaterial delivery of morphogens to mimic the natural healing cascade in bone. Adv. Drug Deliv. Rev. 64, 1257–1276 (2012).

  35. 35.

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

  36. 36.

    et al. Designer matrices for intestinal stem cell and organoid culture. Nature 539, 560–564 (2016).

  37. 37.

    et al. 3D niche microarrays for systems-level analyses of cell fate. Nat. Commun. 5, 4324 (2014).

  38. 38.

    & High-throughput methods to define complex stem cell niches. BioTechniques 48, 9–22 (2010).

  39. 39.

    et al. Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells. Nat. Mater. 9, 768–778 (2010).

  40. 40.

    et al. High throughput methods applied in biomaterial development and discovery. Biomaterials 31, 187–198 (2010).

  41. 41.

    et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat. Biotechnol. 34, 345–352 (2016).

  42. 42.

    et al. Discovery of a novel polymer for human pluripotent stem cell expansion and multilineage differentiation. Adv. Mater. 27, 4006–4012 (2015).

  43. 43.

    , , & Droplet-based microfluidics in drug discovery, transcriptomics and high-throughput molecular genetics. Lab Chip 16, 1314–1331 (2016).

  44. 44.

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

  45. 45.

    & In situ patterning of microfluidic networks in 3d cell-laden hydrogels. Adv. Mater. 28, 7450–7456 (2016).

  46. 46.

    & Modeling and simulation of biomaterials. Annu. Rev. Mater. Res. 34, 279–314 (2004).

  47. 47.

    & in Materiomics: Multiscale Mechanics of Biological Materials and Structures (eds Buehler, M. J. & Ballarini, R.) 13–55 (Springer, 2013).

  48. 48.

    et al. Stents: biomechanics, biomaterials, and insights from computational modeling. Ann. Biomed. Eng. 45, 853–872 (2017).

  49. 49.

    Smart Hydrogel Modelling (Springer, 2009).

  50. 50.

    et al. Hi-C: a comprehensive technique to capture the conformation of genomes. Methods 58, 268–276 (2012).

  51. 51.

    , , , & FAIRE (formaldehyde-assisted isolation of regulatory elements) isolates active regulatory elements from human chromatin. Genome Res. 17, 877–885 (2007).

  52. 52.

    , , , & Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).

  53. 53.

    et al. Systems glycobiology: integrating glycogenomics, glycoproteomics, glycomics, and other 'omics data sets to characterize cellular glycosylation processes. J. Mol. Biol. 428, 3337–3352 (2016).

  54. 54.

    Glycans in regeneration. ACS Chem. Biol. 9, 96–104 (2014).

  55. 55.

    et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214 (2015).

  56. 56.

    et al. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161, 1187–1201.

  57. 57.

    et al. Multiplexed ion beam imaging of human breast tumors. Nat. Med. 20, 436–442 (2014).

  58. 58.

    et al. Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state. Nat. Biotechnol. 33, 1165–1172 (2015).

  59. 59.

    , , , & New tools in cytometry. Morphologie 100, 199–209 (2016).

  60. 60.

    Follow-up review: recent progress in the development of super-resolution optical microscopy. Microscopy 65, 275–281 (2016).

  61. 61.

    et al. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science 346 (2014).

  62. 62.

    et al. Structural and molecular interrogation of intact biological systems. Nature 497, 332–337 (2013).

  63. 63.

    , , & Large-scale image-based screening and profiling of cellular phenotypes. Cytometry Part A 91, 115–125 (2016).

  64. 64.

    et al. What is the greatest regulatory challenge in the translation of biomaterials to the clinic? Sci. Transl. Med. 4, 160cm114 (2012).

  65. 65.

    Difficulties in the translation of functionalized biomaterials into regenerative medicine clinical products. Biomaterials 32, 4215–4217 (2011).

  66. 66.

    & Twenty-first century challenges for biomaterials. J. R. Soc. Interface 7, S379–S391 (2010).

  67. 67.

    & (eds) Regulatory Affairs for Biomaterials and Medical Devices 1st edn (Woodhead, 2014).

  68. 68.

    et al. Stepping into the omics era: opportunities and challenges for biomaterials science and engineering. Acta Biomater. 34, 133–142 (2016).

  69. 69.

    , & Design of experiments applications in bioprocessing: concepts and approach. Biotechnol. Prog. 30, 86–99 (2014).

  70. 70.

    & Bioprocess optimization using design-of-experiments methodology. Biotechnol. Prog. 24, 1191–1203 (2008).

  71. 71.

    , , , & Experimental design methods for bioengineering applications. Crit. Rev. Biotechnol. 36, 368–388 (2016).

  72. 72.

    et al. Intelligent bioprocessing for haemotopoietic cell cultures using monitoring and design of experiments. Biotechnol. Adv. 25, 353–368 (2007).

  73. 73.

    , , & The use of 'omics technology to rationally improve industrial mammalian cell line performance. Biotechnol. Bioeng. 113, 26–38 (2016).

  74. 74.

    , & Genomics in mammalian cell culture bioprocessing. Biotechnol. Adv. 30, 629–638 (2012).

  75. 75.

    & Reverse engineering and identification in systems biology: strategies, perspectives and challenges. J. R. Soc. Interface 11, 20130505 (2014).

  76. 76.

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

  77. 77.

    & Encapsulated islets for diabetes therapy: history, current progress, and critical issues requiring solution. Adv. Drug Deliv. Rev. 67–68, 35–73 (2014).

  78. 78.

    et al. A prevascularized subcutaneous device-less site for islet and cellular transplantation. Nat. Biotechnol. 33, 518–523 (2015).

  79. 79.

    et al. Generation of functional human pancreatic β cells in vitro. Cell 159, 428–439 (2014).

  80. 80.

    et al. Device design and materials optimization of conformal coating for islets of Langerhans. Proc. Natl Acad. Sci. USA 111, 10514–10519 (2014).

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Acknowledgements

The authors would like to acknowledge funding from National Institutes of Health (R01 DE013033; R01 DE013349) and the National Science Foundation funded Materials Research Science and Engineering Centers at Harvard University (DMR-1420570).

Author information

Affiliations

  1. Harvard School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA

    • Max Darnell
    •  & David J. Mooney
  2. Wyss Institute for Biologically Inspired Engineering, Cambridge, Massachusetts 02138, USA

    • Max Darnell
    •  & David J. Mooney

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David J. Mooney.