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Biomaterial-based platforms for tumour tissue engineering

Nature Reviews Materials volume 8, pages 314–330 (2023)Cite this article

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Abstract

Tissue engineering has produced innovative tools for cancer research. 3D cancer models based on molecularly designed biomaterials aim to harness the dimensionality and biomechanical and biochemical properties of tumour tissues. However, to date, despite the critical role that the extracellular matrix plays in cancer, only a minority of 3D cancer models are built on biomaterial-based matrices. Major reasons for avoiding this critical design feature are the difficulty in recreating the inherent complexity of the tumour microenvironment and the limited availability of practical analytical and validation techniques. Recent advances emerging at the interface of supramolecular chemistry, materials science and tumour biology are generating new approaches to overcome these boundaries and enable the design of physiologically relevant 3D models. Here, we discuss how these 3D systems are applied to deconstruct and engineer the tumour microenvironment, opening opportunities to model primary tumours, metastasis and responses to anticancer treatment.

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Fig. 1: Concept of tumour tissue engineering.
Fig. 2: Applications of tumour-engineered models to investigate primary tumours, metastasis and anticancer treatment.
Fig. 3: Bioengineering the pre-metastatic and metastatic niche.
Fig. 4: Convergence of tissue engineering and tumour biology.

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References

  1. Tomás-Bort, E., Kieler, M., Sharma, S., Candido, J. B. & Loessner, D. 3D approaches to model the tumor microenvironment of pancreatic cancer. Theranostics 10, 5074–5089 (2020).

    Article  Google Scholar 

  2. Fischbach, C. et al. Engineering tumors with 3D scaffolds. Nat. Methods 4, 855–860 (2007).

    Article  CAS  Google Scholar 

  3. Loessner, D. et al. A 3D tumor microenvironment regulates cell proliferation, peritoneal growth and expression patterns. Biomaterials 190–191, 63–75 (2019).

    Article  Google Scholar 

  4. Loessner, D. et al. Bioengineered 3D platform to explore cell–ECM interactions and drug resistance of epithelial ovarian cancer cells. Biomaterials 31, 8494–8506 (2010).

    Article  CAS  Google Scholar 

  5. Loessner, D. et al. Functionalization, preparation and use of cell-laden gelatin methacryloyl-based hydrogels as modular tissue culture platforms. Nat. Protoc. 11, 727–746 (2016).

    Article  CAS  Google Scholar 

  6. Hedegaard, C. L. et al. Peptide-protein coassembling matrices as a biomimetic 3D model of ovarian cancer. Sci. Adv. 6, eabb3298 (2020).

    Article  CAS  Google Scholar 

  7. Osuna de la Peña, D. et al. Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology. Nat. Commun. 12, 5623 (2021).

    Article  Google Scholar 

  8. Kast, V. et al. A tumor microenvironment model of pancreatic cancer to elucidate responses toward immunotherapy. Adv. Healthc. Mater. https://doi.org/10.1002/adhm.202201907 (2022).

    Article  Google Scholar 

  9. Loessner, D. et al. A bioengineered 3D ovarian cancer model for the assessment of peptidase-mediated enhancement of spheroid growth and intraperitoneal spread. Biomaterials 34, 7389–7400 (2013).

    Article  CAS  Google Scholar 

  10. Holzapfel, B. M. et al. Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone. Biomaterials 35, 4108–4115 (2014).

    Article  CAS  Google Scholar 

  11. DelNero, P. et al. 3D culture broadly regulates tumor cell hypoxia response and angiogenesis via pro-inflammatory pathways. Biomaterials 55, 110–118 (2015).

    Article  CAS  Google Scholar 

  12. Bray, L. J. et al. Multi-parametric hydrogels support 3D in vitro bioengineered microenvironment models of tumour angiogenesis. Biomaterials 53, 609–620 (2015).

    Article  CAS  Google Scholar 

  13. Taubenberger, A. V. et al. 3D extracellular matrix interactions modulate tumour cell growth, invasion and angiogenesis in engineered tumour microenvironments. Acta Biomater. 36, 73–85 (2016).

    Article  CAS  Google Scholar 

  14. Malacrida, B. et al. A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion. iScience 24, 102676 (2021).

    Article  CAS  Google Scholar 

  15. Colombo, M. V. et al. Engineering the early bone metastatic niche through human vascularized immuno bone minitissues. Biofabrication 13, 035036 (2021).

    Article  CAS  Google Scholar 

  16. Sameni, M. et al. MAME models for 4D live-cell imaging of tumor: microenvironment interactions that impact malignant progression. J. Vis. Exp. https://doi.org/10.3791/3661 (2012).

    Article  Google Scholar 

  17. Sameni, M. et al. Pathomimetic avatars reveal divergent roles of microenvironment in invasive transition of ductal carcinoma in situ. Breast Cancer Res. 19, 56 (2017).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Liu, A. P. et al. The living interface between synthetic biology and biomaterial design. Nat. Mater. 21, 390–397 (2022).

    Article  CAS  Google Scholar 

  20. Hutmacher, D. W. et al. Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance. Curr. Opin. Biotechnol. 35, 127–132 (2015).

    Article  CAS  Google Scholar 

  21. Ingber, D. E. Reverse engineering human pathophysiology with organs-on-chips. Cell 164, 1105–1109 (2016).

    Article  CAS  Google Scholar 

  22. Simian, M. & Bissell, M. J. Organoids: a historical perspective of thinking in three dimensions. J. Cell Biol. 216, 31–40 (2017).

    Article  CAS  Google Scholar 

  23. Albritton, J. L. & Miller, J. S. 3D bioprinting: improving in vitro models of metastasis with heterogeneous tumor microenvironments. Dis. Model. Mech. 10, 3–14 (2017).

    Article  CAS  Google Scholar 

  24. Weiden, J., Tel, J. & Figdor, C. G. Synthetic immune niches for cancer immunotherapy. Nat. Rev. Immunol. 18, 212–219 (2018).

    Article  CAS  Google Scholar 

  25. Liu, H.-Y., Korc, M. & Lin, C.-C. Biomimetic and enzyme-responsive dynamic hydrogels for studying cell–matrix interactions in pancreatic ductal adenocarcinoma. Biomaterials 160, 24–36 (2018).

    Article  CAS  Google Scholar 

  26. Hanahan, D. Hallmarks of cancer: new dimensions. Cancer Discov. 12, 31–46 (2022).

    Article  CAS  Google Scholar 

  27. Labani-Motlagh, A., Ashja-Mahdavi, M. & Loskog, A. The tumor microenvironment: a milieu hindering and obstructing antitumor immune responses. Front. Immunol. 11, 940 (2020).

    Article  CAS  Google Scholar 

  28. Cox, T. R. The matrix in cancer. Nat. Rev. Cancer 21, 217–238 (2021).

    Article  CAS  Google Scholar 

  29. Pearce, O. M. T. et al. Deconstruction of a metastatic tumor microenvironment reveals a common matrix response in human cancers. Cancer Discov. 8, 304–319 (2018).

    Article  CAS  Google Scholar 

  30. Grünwald, B. T. et al. Spatially confined sub-tumor microenvironments in pancreatic cancer. Cell 184, 5577–5592.e18 (2021).

    Article  Google Scholar 

  31. Below, C. R. et al. A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids. Nat. Mater. 21, 110–119 (2022).

    Article  CAS  Google Scholar 

  32. Thorsson, V. et al. The immune landscape of cancer. Immunity 48, 812–830.e14 (2018).

    Article  CAS  Google Scholar 

  33. Duan, Q., Zhang, H., Zheng, J. & Zhang, L. Turning cold into hot: firing up the tumor microenvironment. Trends Cancer 6, 605–618 (2020).

    Article  CAS  Google Scholar 

  34. Tian, C. et al. Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveal different contributions by tumor and stromal cells. Proc. Natl Acad. Sci. USA 116, 19609 (2019).

    Article  CAS  Google Scholar 

  35. Rice, A. J. et al. Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells. Oncogenesis 6, e352 (2017).

    Article  CAS  Google Scholar 

  36. Choi, S. et al. Intrafibrillar, bone-mimetic collagen mineralization regulates breast cancer cell adhesion and migration. Biomaterials 198, 95–106 (2019).

    Article  CAS  Google Scholar 

  37. Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K. J. & Werb, Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat. Commun. 11, 5120 (2020).

    Article  CAS  Google Scholar 

  38. Xu, K. et al. 3D porous chitosan-alginate scaffold stiffness promotes differential responses in prostate cancer cell lines. Biomaterials 217, 119311 (2019).

    Article  CAS  Google Scholar 

  39. Yue, X., Nguyen, T. D., Zellmer, V., Zhang, S. & Zorlutuna, P. Stromal cell-laden 3D hydrogel microwell arrays as tumor microenvironment model for studying stiffness dependent stromal cell–cancer interactions. Biomaterials 170, 37–48 (2018).

    Article  CAS  Google Scholar 

  40. Ling, L. et al. Obesity-associated adipose stromal cells promote breast cancer invasion through direct cell contact and ECM remodeling. Adv. Funct. Mater. 30, 1910650 (2020).

    Article  CAS  Google Scholar 

  41. Srinivasan, S., Kryza, T., Batra, J. & Clements, J. Remodelling of the tumour microenvironment by the kallikrein-related peptidases. Nat. Rev. Cancer 22, 223–238 (2022).

    Article  CAS  Google Scholar 

  42. Candido, J. B. et al. Kallikrein-related peptidase 6 is associated with the tumour microenvironment of pancreatic ductal adenocarcinoma. Cancers 13, 3969 (2021).

    Article  CAS  Google Scholar 

  43. Loessner, D. et al. Kallikrein-related peptidases represent attractive therapeutic targets for ovarian cancer. Exp. Opin. Ther. Targets 22, 745–763 (2018).

    Article  CAS  Google Scholar 

  44. Wang, Z. et al. 3D-organoid culture supports differentiation of human CAR(+) iPSCs into highly functional CAR T cells. Cell Stem Cell 29, 515–527.e18 (2022).

    Article  Google Scholar 

  45. Steele, N. G. et al. Multimodal mapping of the tumor and peripheral blood immune landscape in human pancreatic cancer. Nat. Cancer 1, 1097–1112 (2020).

    Article  CAS  Google Scholar 

  46. Bear, A. S., Vonderheide, R. H. & O’Hara, M. H. Challenges and opportunities for pancreatic cancer immunotherapy. Cancer Cell 38, 788–802 (2020).

    Article  CAS  Google Scholar 

  47. Ayuso Jose, M. et al. Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion. Sci. Adv. 7, eabc2331 (2021).

    Article  Google Scholar 

  48. Neal, J. T. et al. Organoid modeling of the tumor immune microenvironment. Cell 175, 1972–1988.e16 (2018).

    Article  CAS  Google Scholar 

  49. Liu, B. et al. Temporal single-cell tracing reveals clonal revival and expansion of precursor exhausted T cells during anti-PD-1 therapy in lung cancer. Nat. Cancer 3, 108–121 (2022).

    Article  CAS  Google Scholar 

  50. Duraiswamy, J. et al. Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation. Cancer Cell 39, 1623–1642.e20 (2021).

    Article  CAS  Google Scholar 

  51. Rebelo, S. P. et al. 3D-3-culture: a tool to unveil macrophage plasticity in the tumour microenvironment. Biomaterials 163, 185–197 (2018).

    Article  CAS  Google Scholar 

  52. Cui, X. et al. Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis. Biomaterials 161, 164–178 (2018).

    Article  CAS  Google Scholar 

  53. Quail, D. F. & Dannenberg, A. J. The obese adipose tissue microenvironment in cancer development and progression. Nat. Rev. Endocrinol. 15, 139–154 (2019).

    Article  Google Scholar 

  54. Mukherjee, A. et al. Adipocyte-induced FABP4 expression in ovarian cancer cells promotes metastasis and mediates carboplatin resistance. Cancer Res. 80, 1748 (2020).

    Article  CAS  Google Scholar 

  55. Guimarães, C. F., Gasperini, L., Marques, A. P. & Reis, R. L. The stiffness of living tissues and its implications for tissue engineering. Nat. Rev. Mater. 5, 351–370 (2020).

    Article  Google Scholar 

  56. Okesola, B. O. & Mata, A. Multicomponent self-assembly as a tool to harness new properties from peptides and proteins in material design. Chem. Soc. Rev. 47, 3721–3736 (2018).

    Article  CAS  Google Scholar 

  57. Panja, S., Dietrich, B., Shebanova, O., Smith, A. J. & Adams, D. J. Programming gels over a wide pH range using multicomponent systems. Angew. Chem. Int. Ed. Engl. 60, 9973–9977 (2021).

    Article  CAS  Google Scholar 

  58. Mendoza-Martinez, A. K., Loessner, D., Mata, A. & Azevedo, H. S. Modeling the tumor microenvironment of ovarian cancer: the application of self-assembling biomaterials. Cancers 13, 5745 (2021).

    Article  CAS  Google Scholar 

  59. Redondo-Gomez, C., Abdouni, Y., Becer, C. R. & Mata, A. Self-assembling hydrogels based on a complementary host–guest peptide amphiphile pair. Biomacromolecules 20, 2276–2285 (2019).

    Article  CAS  Google Scholar 

  60. Edelbrock, A. N. et al. Superstructured biomaterials formed by exchange dynamics and host–guest interactions in supramolecular polymers. Adv. Sci. 8, 2004042 (2021).

    Article  CAS  Google Scholar 

  61. Blache, U., Stevens, M. M. & Gentleman, E. Harnessing the secreted extracellular matrix to engineer tissues. Nat. Biomed. Eng. 4, 357–363 (2020).

    Article  Google Scholar 

  62. Freeman, R. et al. Reversible self-assembly of superstructured networks. Science 362, 808–813 (2018).

    Article  CAS  Google Scholar 

  63. Redondo-Gomez, C., Padilla-Lopategui, S., Azevedo, H. S. & Mata, A. Host–guest-mediated epitope presentation on self-assembled peptide amphiphile hydrogels. ACS Biomater. Sci. Eng. 6, 4870–4880 (2020).

    Article  CAS  Google Scholar 

  64. Okesola, B. O. et al. Supramolecular self-assembly to control structural and biological properties of multicomponent hydrogels. Chem. Mater. 31, 7883–7897 (2019).

    Article  CAS  Google Scholar 

  65. Hermida, M. A. et al. Three dimensional in vitro models of cancer: bioprinting multilineage glioblastoma models. Adv. Biol. Regul. 75, 100658 (2020).

    Article  CAS  Google Scholar 

  66. Curvello, R. et al. 3D collagen–nanocellulose matrices model the tumour microenvironment of pancreatic cancer. Front. Digit. Health 3, 704584 (2021).

    Article  Google Scholar 

  67. Trujillo, S. et al. Engineered full-length fibronectin-hyaluronic acid hydrogels for stem cell engineering. Adv. Healthc. Mater. 9, e2000989 (2020).

    Article  Google Scholar 

  68. Sarrigiannidis, S. O. et al. A tough act to follow: collagen hydrogel modifications to improve mechanical and growth factor loading capabilities. Mater. Today Bio 10, 100098 (2021).

    Article  CAS  Google Scholar 

  69. Seo, B. R. et al. Collagen microarchitecture mechanically controls myofibroblast differentiation. Proc. Natl Acad. Sci. USA 117, 11387 (2020).

    Article  CAS  Google Scholar 

  70. Drost, J. & Clevers, H. Organoids in cancer research. Nat. Rev. Cancer 18, 407–418 (2018).

    Article  CAS  Google Scholar 

  71. Freudenberg, U., Liang, Y., Kiick, K. L. & Werner, C. Glycosaminoglycan-based biohybrid hydrogels: a sweet and smart choice for multifunctional biomaterials. Adv. Mater. 28, 8861–8891 (2016).

    Article  CAS  Google Scholar 

  72. Anjum, F. et al. Enzyme responsive GAG-based natural-synthetic hybrid hydrogel for tunable growth factor delivery and stem cell differentiation. Biomaterials 87, 104–117 (2016).

    Article  CAS  Google Scholar 

  73. Binner, M. et al. Cell-instructive starPEG–heparin–collagen composite matrices. Acta Biomater. 53, 70–80 (2017).

    Article  CAS  Google Scholar 

  74. Chaudhuri, O., Cooper-White, J., Janmey, P. A., Mooney, D. J. & Shenoy, V. B. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 584, 535–546 (2020).

    Article  CAS  Google Scholar 

  75. Berger, A. J., Linsmeier, K. M., Kreeger, P. K. & Masters, K. S. Decoupling the effects of stiffness and fiber density on cellular behaviors via an interpenetrating network of gelatin-methacrylate and collagen. Biomaterials 141, 125–135 (2017).

    Article  CAS  Google Scholar 

  76. Guzman, A., Sanchez Alemany, V., Nguyen, Y., Zhang, C. R. & Kaufman, L. J. A novel 3D in vitro metastasis model elucidates differential invasive strategies during and after breaching basement membrane. Biomaterials 115, 19–29 (2017).

    Article  CAS  Google Scholar 

  77. Nguyen, E. H. et al. Versatile synthetic alternatives to Matrigel for vascular toxicity screening and stem cell expansion. Nat. Biomed. Eng. 1, 0096 (2017).

    Article  CAS  Google Scholar 

  78. O’Melia, M. J. et al. Synthetic matrix scaffolds engineer the in vivo tumor immune microenvironment for immunotherapy screening. Adv. Mater. 34, e2108084 (2022).

    Article  Google Scholar 

  79. Aisenbrey, E. A. & Murphy, W. L. Synthetic alternatives to matrigel. Nat. Rev. Mater. 5, 539–551 (2020).

    Article  CAS  Google Scholar 

  80. Place, E. S., Evans, N. D. & Stevens, M. M. Complexity in biomaterials for tissue engineering. Nat. Mater. 8, 457–470 (2009).

    Article  CAS  Google Scholar 

  81. Limasale, Y. D. P., Atallah, P., Werner, C., Freudenberg, U. & Zimmermann, R. Tuning the local availability of VEGF within glycosaminoglycan-based hydrogels to modulate vascular endothelial cell morphogenesis. Adv. Funct. Mater. 30, 2000068 (2020).

    Article  CAS  Google Scholar 

  82. Khademhosseini, A. & Langer, R. A decade of progress in tissue engineering. Nat. Protoc. 11, 1775–1781 (2016).

    Article  CAS  Google Scholar 

  83. Ootani, A. et al. Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat. Med. 15, 701–706 (2009).

    Article  CAS  Google Scholar 

  84. Sato, T. et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262–265 (2009).

    Article  CAS  Google Scholar 

  85. LeSavage, B. L., Suhar, R. A., Broguiere, N., Lutolf, M. P. & Heilshorn, S. C. Next-generation cancer organoids. Nat. Mater. 21, 143–159 (2021).

    Article  Google Scholar 

  86. Hofer, M. & Lutolf, M. P. Engineering organoids. Nat. Rev. Mater. 6, 402–420 (2021).

    Article  CAS  Google Scholar 

  87. van Neerven, S. M. & Vermeulen, L. Cell competition in development, homeostasis and cancer. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/s41580-022-00538-y (2022).

    Article  Google Scholar 

  88. Pothapragada, S. P., Gupta, P., Mukherjee, S. & Das, T. Matrix mechanics regulates epithelial defence against cancer by tuning dynamic localization of filamin. Nat. Commun. 13, 218 (2022).

    Article  CAS  Google Scholar 

  89. Nam, S., Stowers, R., Lou, J., Xia, Y. & Chaudhuri, O. Varying PEG density to control stress relaxation in alginate-PEG hydrogels for 3D cell culture studies. Biomaterials 200, 15–24 (2019).

    Article  CAS  Google Scholar 

  90. Neves, M. I., Moroni, L. & Barrias, C. C. Modulating alginate hydrogels for improved biological performance as cellular 3D microenvironments. Front. Bioeng. Biotechnol. 8, 665 (2020).

    Article  Google Scholar 

  91. Andersen, T., Auk-Emblem, P. & Dornish, M. 3D cell culture in alginate hydrogels. Microarrays 4, 133–161 (2015).

    Article  CAS  Google Scholar 

  92. Ning, L. et al. 3D bioprinting of scaffolds with living Schwann cells for potential nerve tissue engineering applications. Biofabrication 10, 035014 (2018).

    Article  Google Scholar 

  93. Mosquera, M. J. et al. Extracellular matrix in synthetic hydrogel-based prostate cancer organoids regulate therapeutic response to EZH2 and DRD2 inhibitors. Adv. Mater. 34, e2100096 (2022).

    Article  Google Scholar 

  94. Mahajan, V. et al. Mapping tumor spheroid mechanics in dependence of 3D microenvironment stiffness and degradability by brillouin microscopy. Cancers 13, 5549 (2021).

    Article  CAS  Google Scholar 

  95. Prince, E. et al. Biomimetic hydrogel supports initiation and growth of patient-derived breast tumor organoids. Nat. Commun. 13, 1466 (2022).

    Article  CAS  Google Scholar 

  96. Horst, E. N. et al. Injectable three-dimensional tumor microenvironments to study mechanobiology in ovarian cancer. Acta Biomater. 146, 222–234 (2022).

    Article  CAS  Google Scholar 

  97. Elia, I. & Haigis, M. C. Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism. Nat. Metab. 3, 21–32 (2021).

    Article  Google Scholar 

  98. Raho, S. et al. KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth. Nat. Metab. 2, 1373–1381 (2020).

    Article  CAS  Google Scholar 

  99. Coassolo, S. et al. Citrullination of pyruvate kinase M2 by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation. Nat. Commun. 12, 1718 (2021).

    Article  CAS  Google Scholar 

  100. Park, M. K. et al. NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis. Cell Metab. 33, 2380–2397.e9 (2021).

    Article  CAS  Google Scholar 

  101. Bertero, T. et al. Tumor–stroma mechanics coordinate amino acid availability to sustain tumor growth and malignancy. Cell Metab. 29, 124–140.e10 (2019).

    Article  CAS  Google Scholar 

  102. Biancur, D. E. et al. Functional genomics identifies metabolic vulnerabilities in pancreatic cancer. Cell Metab. 33, 199–210.e8 (2021).

    Article  CAS  Google Scholar 

  103. Broekgaarden, M. et al. Modulation of redox metabolism negates cancer-associated fibroblasts-induced treatment resistance in a heterotypic 3D culture platform of pancreatic cancer. Biomaterials 222, 119421 (2019).

    Article  CAS  Google Scholar 

  104. Sharma, N. S. et al. Targeting tumor-intrinsic hexosamine biosynthesis sensitizes pancreatic cancer to anti-PD1 therapy. J. Clin. Invest. 130, 451–465 (2020).

    Article  CAS  Google Scholar 

  105. Chen, D., Zhang, X., Li, Z. & Zhu, B. Metabolic regulatory crosstalk between tumor microenvironment and tumor-associated macrophages. Theranostics 11, 1016–1030 (2021).

    Article  CAS  Google Scholar 

  106. Cho, H. et al. Cancer-stimulated CAFs enhance monocyte differentiation and protumoral TAM activation via IL6 and GM-CSF secretion. Clin. Cancer Res. 24, 5407 (2018).

    Article  CAS  Google Scholar 

  107. Lin, W. et al. Function of CSF1 and IL34 in macrophage homeostasis, inflammation, and cancer. Front. Immunol. 10, 2019 (2019).

    Article  CAS  Google Scholar 

  108. House, I. G. et al. Macrophage-derived CXCL9 and CXCL10 are required for antitumor immune responses following immune checkpoint blockade. Clin. Cancer Res. 26, 487 (2020).

    Article  CAS  Google Scholar 

  109. Unterleuthner, D. et al. Cancer-associated fibroblast-derived WNT2 increases tumor angiogenesis in colon cancer. Angiogenesis 23, 159–177 (2020).

    Article  CAS  Google Scholar 

  110. Stuelten, C. H., Parent, C. A. & Montell, D. J. Cell motility in cancer invasion and metastasis: insights from simple model organisms. Nat. Rev. Cancer 18, 296–312 (2018).

    Article  CAS  Google Scholar 

  111. Marcelin, G., Silveira, A. L. M., Martins, L. B., Ferreira, A. V. M. & Clément, K. Deciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis. J. Clin. Invest. 129, 4032–4040 (2019).

    Article  Google Scholar 

  112. Zhang, W. et al. The bone microenvironment invigorates metastatic seeds for further dissemination. Cell 184, 2471–2486.e20 (2021).

    Article  CAS  Google Scholar 

  113. Monteran, L. et al. Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis. Sci. Rep. 10, 13838 (2020).

    Article  CAS  Google Scholar 

  114. González Díaz, E. C., Sinha, S., Avedian, R. S. & Yang, F. Tissue-engineered 3D models for elucidating primary and metastatic bone cancer progression. Acta Biomater. 99, 18–32 (2019).

    Article  Google Scholar 

  115. Hofbauer, L. C. et al. Novel approaches to target the microenvironment of bone metastasis. Nat. Rev. Clin. Oncol. 18, 488–505 (2021).

    Article  Google Scholar 

  116. Han, W. et al. In vitro bone metastasis dwelling in a 3D bioengineered niche. Biomaterials 269, 120624 (2021).

    Article  CAS  Google Scholar 

  117. Chen, L. et al. Tumor-secreted GRP78 promotes the establishment of a pre-metastatic niche in the liver microenvironment. Front. Immunol. 11, 2544 (2020).

    Article  Google Scholar 

  118. Chen, C. et al. Dahuang Zhechong Pill suppresses colorectal cancer liver metastasis via ameliorating exosomal CCL2 primed pre-metastatic niche. J. Ethnopharmacol. 238, 111878 (2019).

    Article  Google Scholar 

  119. Zheng, Y. et al. XIAOPI formula inhibits the pre-metastatic niche formation in breast cancer via suppressing TAMs/CXCL1 signaling. Cell Commun. Signal. 18, 48 (2020).

    Article  CAS  Google Scholar 

  120. Chen, X. W. et al. CYP4A in tumor-associated macrophages promotes pre-metastatic niche formation and metastasis. Oncogene 36, 5045–5057 (2017).

    Article  CAS  Google Scholar 

  121. Anlaş, A. A. & Nelson, C. M. Soft microenvironments induce chemoresistance by increasing autophagy downstream of integrin-linked kinase. Cancer Res. 80, 4103 (2020).

    Article  Google Scholar 

  122. Peinado, H. et al. Pre-metastatic niches: organ-specific homes for metastases. Nat. Rev. Cancer 17, 302–317 (2017).

    Article  CAS  Google Scholar 

  123. Naba, A. et al. Characterization of the extracellular matrix of normal and diseased tissues using proteomics. J. Proteome Res. 16, 3083–3091 (2017).

    Article  CAS  Google Scholar 

  124. Ravichandran, A., Meinert, C., Bas, O., Hutmacher, D. W. & Bock, N. Engineering a 3D bone marrow adipose composite tissue loading model suitable for studying mechanobiological questions. Mater. Sci. Eng. C 128, 112313 (2021).

    Article  CAS  Google Scholar 

  125. Cui, Z.-K. et al. Microporous methacrylated glycol chitosan-montmorillonite nanocomposite hydrogel for bone tissue engineering. Nat. Commun. 10, 3523 (2019).

    Article  Google Scholar 

  126. Romero-Moreno, R. et al. The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis. Nat. Commun. 10, 4404 (2019).

    Article  Google Scholar 

  127. Massagué, J. & Obenauf, A. C. Metastatic colonization by circulating tumour cells. Nature 529, 298–306 (2016).

    Article  Google Scholar 

  128. Wang, Y. et al. Metastasis-on-a-chip mimicking the progression of kidney cancer in the liver for predicting treatment efficacy. Theranostics 10, 300–311 (2020).

    Article  Google Scholar 

  129. Rafaeva, M. et al. Modeling metastatic colonization in a decellularized organ scaffold-based perfusion bioreactor. Adv. Healthc. Mater. 11, e2100684 (2022).

    Article  Google Scholar 

  130. Yu, J. et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nat. Med. 27, 152–164 (2021).

    Article  CAS  Google Scholar 

  131. Marturano-Kruik, A. et al. Human bone perivascular niche-on-a-chip for studying metastatic colonization. Proc. Natl Acad. Sci. USA 115, 1256 (2018).

    Article  CAS  Google Scholar 

  132. Brylka, L. J. & Schinke, T. Chemokines in physiological and pathological bone remodeling. Front. Immunol. 10, 2182 (2019).

    Article  CAS  Google Scholar 

  133. Bouchet, M. et al. ERRα expression in bone metastases leads to an exacerbated antitumor immune response. Cancer Res. 80, 2914 (2020).

    Article  CAS  Google Scholar 

  134. Yao, Y. et al. Patient-derived organoids predict chemoradiation responses of locally advanced rectal cancer. Cell Stem Cell 26, 17–26.e6 (2020).

    Article  CAS  Google Scholar 

  135. Driehuis, E., Kretzschmar, K. & Clevers, H. Establishment of patient-derived cancer organoids for drug-screening applications. Nat. Protoc. 15, 3380–3409 (2020).

    Article  CAS  Google Scholar 

  136. Ganesh, K. et al. A rectal cancer organoid platform to study individual responses to chemoradiation. Nat. Med. 25, 1607–1614 (2019).

    Article  CAS  Google Scholar 

  137. Norkin, M., Ordonez-Moran, P. & Huelsken, J. High-content, targeted RNA-seq screening in organoids for drug discovery in colorectal cancer. Cell Rep. 35, 109026 (2021).

    Article  CAS  Google Scholar 

  138. Brandenberg, N. et al. High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays. Nat. Biomed. Eng. 4, 863–874 (2020).

    Article  CAS  Google Scholar 

  139. Jung, Y. H. et al. Drug screening by uniform patient derived colorectal cancer hydro-organoids. Biomaterials 276, 121004 (2021).

    Article  CAS  Google Scholar 

  140. Monteiro, C. F., Custódio, C. A. & Mano, J. F. Bioengineering a humanized 3D tri-culture osteosarcoma model to assess tumor invasiveness and therapy response. Acta Biomater. 134, 204–214 (2021).

    Article  CAS  Google Scholar 

  141. Antunes, J. et al. In-air production of 3D co-culture tumor spheroid hydrogels for expedited drug screening. Acta Biomater. 94, 392–409 (2019).

    Article  CAS  Google Scholar 

  142. Labat, B. et al. Biomimetic matrix for the study of neuroblastoma cells: a promising combination of stiffness and retinoic acid. Acta Biomater. 135, 383–392 (2021).

    Article  CAS  Google Scholar 

  143. Prince, E. et al. Microfluidic arrays of breast tumor spheroids for drug screening and personalized cancer therapies. Adv. Healthc. Mater. 11, e2101085 (2022).

    Article  Google Scholar 

  144. Eggermont, A. M. M. et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 22, 643–654 (2021).

    Article  CAS  Google Scholar 

  145. Schmid, P. et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 379, 2108–2121 (2018).

    Article  CAS  Google Scholar 

  146. Horn, L. et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N. Engl. J. Med. 379, 2220–2229 (2018).

    Article  CAS  Google Scholar 

  147. Nevala-Plagemann, C., Hidalgo, M. & Garrido-Laguna, I. From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer. Nat. Rev. Clin. Oncol. 17, 108–123 (2020).

    Article  Google Scholar 

  148. Mollica, H. et al. A 3D pancreatic tumor model to study T cell infiltration. Biomater. Sci. 9, 7420–7431 (2021).

    Article  CAS  Google Scholar 

  149. Sontheimer-Phelps, A., Hassell, B. A. & Ingber, D. E. Modelling cancer in microfluidic human organs-on-chips. Nat. Rev. Cancer 19, 65–81 (2019).

    Article  CAS  Google Scholar 

  150. Kim, D. et al. Vascularized lung cancer model for evaluating the promoted transport of anticancer drugs and immune cells in an engineered tumor microenvironment. Adv. Healthc. Mater. 11, e2102581 (2022).

    Article  Google Scholar 

  151. Huinen, Z. R., Huijbers, E. J. M., van Beijnum, J. R., Nowak-Sliwinska, P. & Griffioen, A. W. Anti-angiogenic agents — overcoming tumour endothelial cell anergy and improving immunotherapy outcomes. Nat. Rev. Clin. Oncol. 18, 527–540 (2021).

    Article  Google Scholar 

  152. Wunner, F. M. et al. Melt electrospinning writing of highly ordered large volume scaffold architectures. Adv. Mater. 30, e1706570 (2018).

    Article  Google Scholar 

  153. Wagner, F. et al. Humanization of bone and bone marrow in an orthotopic site reveals new potential therapeutic targets in osteosarcoma. Biomaterials 171, 230–246 (2018).

    Article  CAS  Google Scholar 

  154. Gavin, C. et al. Neuroblastoma invasion strategies are regulated by the extracellular matrix. Cancers 13, 736 (2021).

    Article  CAS  Google Scholar 

  155. Villasante, A. et al. Recapitulating the size and cargo of tumor exosomes in a tissue-engineered model. Theranostics 6, 1119–1130 (2016).

    Article  CAS  Google Scholar 

  156. Moroni, L. et al. Biofabrication strategies for 3D in vitro models and regenerative medicine. Nat. Rev. Mater. 3, 21–37 (2018).

    Article  CAS  Google Scholar 

  157. Gaspar, V. M., Lavrador, P., Borges, J., Oliveira, M. B. & Mano, J. F. Advanced bottom-up engineering of living architectures. Adv. Mater. 32, e1903975 (2020).

    Article  Google Scholar 

  158. Hedegaard, C. L. & Mata, A. Integrating self-assembly and biofabrication for the development of structures with enhanced complexity and hierarchical control. Biofabrication 12, 032002 (2020).

    Article  CAS  Google Scholar 

  159. Humphries, B. A. et al. Ultrasound-induced mechanical compaction in acoustically responsive scaffolds promotes spatiotemporally modulated signaling in triple negative breast cancer. Adv. Healthc. Mater. 11, e2101672 (2022).

    Article  Google Scholar 

  160. Tibbits, S. 4D printing: multi-material shape change. Archit. Des. 84, 116–121 (2014).

    Google Scholar 

  161. Kirillova, A., Maxson, R., Stoychev, G., Gomillion, C. T. & Ionov, L. 4D biofabrication using shape-morphing hydrogels. Adv. Mater. https://doi.org/10.1002/adma.201703443 (2017).

    Article  Google Scholar 

  162. Vinson, B. T. et al. Laser direct-write based fabrication of a spatially-defined, biomimetic construct as a potential model for breast cancer cell invasion into adipose tissue. Biofabrication 9, 025013 (2017).

    Article  Google Scholar 

  163. Brancato, V. et al. Bioengineered tumoral microtissues recapitulate desmoplastic reaction of pancreatic cancer. Acta Biomater. 49, 152–166 (2017).

    Article  CAS  Google Scholar 

  164. Vennin, C. et al. Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci. Transl. Med. 9, eaai8504 (2017).

    Article  Google Scholar 

  165. Graham, A. D. et al. High-resolution patterned cellular constructs by droplet-based 3D printing. Sci. Rep. 7, 7004 (2017).

    Article  Google Scholar 

  166. Pradhan, S., Clary, J. M., Seliktar, D. & Lipke, E. A. A three-dimensional spheroidal cancer model based on PEG-fibrinogen hydrogel microspheres. Biomaterials 115, 141–154 (2017).

    Article  CAS  Google Scholar 

  167. Valdez, J. et al. On-demand dissolution of modular, synthetic extracellular matrix reveals local epithelial–stromal communication networks. Biomaterials 130, 90–103 (2017).

    Article  CAS  Google Scholar 

  168. Laronda, M. M. et al. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nat. Commun. 8, 15261 (2017).

    Article  CAS  Google Scholar 

  169. Sawicki, L. A. et al. Tunable synthetic extracellular matrices to investigate breast cancer response to biophysical and biochemical cues. APL Bioeng. 3, 016101 (2019).

    Article  Google Scholar 

  170. Bray, L. J. et al. Three-dimensional in vitro hydro- and cryogel-based cell-culture models for the study of breast-cancer metastasis to bone. Cancers 10, 292 (2018).

    Article  Google Scholar 

  171. Ovadia, E. M. et al. Understanding ER+ breast cancer dormancy using bioinspired synthetic matrices for long-term 3D culture and insights into late recurrence. Adv. Biosyst. 4, 2000119 (2020).

    Article  CAS  Google Scholar 

  172. Zhou, N. et al. Effect of RGD content in poly(ethylene glycol)-crosslinked poly(methyl vinyl ether-alt-maleic acid) hydrogels on the expansion of ovarian cancer stem-like cells. Mater. Sci. Eng. C 118, 111477 (2021).

    Article  CAS  Google Scholar 

  173. Solano, A. G. et al. An alginate-based macroporous hydrogel matrix to trap cancer cells. Carbohydr. Polym. 266, 118115 (2021).

    Article  CAS  Google Scholar 

  174. Wolf, K. J. et al. A mode of cell adhesion and migration facilitated by CD44-dependent microtentacles. Proc. Natl Acad. Sci. USA 117, 11432 (2020).

    Article  CAS  Google Scholar 

  175. Chia, J. Y., Miki, T., Mihara, H. & Tsutsumi, H. Biofunctional supramolecular hydrogels fabricated from a short self-assembling peptide modified with bioactive sequences for the 3D culture of breast cancer MCF-7 cells. Bioorg. Med. Chem. 46, 116345 (2021).

    Article  CAS  Google Scholar 

  176. Weiss, M. S. et al. The impact of adhesion peptides within hydrogels on the phenotype and signaling of normal and cancerous mammary epithelial cells. Biomaterials 33, 3548–3559 (2012).

    Article  CAS  Google Scholar 

  177. Reis, E. M. D., Berti, F. V., Colla, G. & Porto, L. M. Bacterial nanocellulose-IKVAV hydrogel matrix modulates melanoma tumor cell adhesion and proliferation and induces vasculogenic mimicry in vitro. J. Biomed. Mater. Res. B Appl. Biomater. 106, 2741–2749 (2018).

    Article  CAS  Google Scholar 

  178. Hughes, C. S., Postovit, L. M. & Lajoie, G. A. Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10, 1886–1890 (2010).

    Article  CAS  Google Scholar 

  179. Passaniti, A., Kleinman, H. K. & Martin, G. R. Matrigel: history/background, uses, and future applications. J. Cell Commun. Signal. 16, 621–626 (2022).

    Article  CAS  Google Scholar 

  180. Curvello, R. et al. Engineered plant-based nanocellulose hydrogel for small intestinal organoid growth. Adv. Sci. 8, 2002135 (2021).

    Article  CAS  Google Scholar 

  181. Rubiano, A. et al. Viscoelastic properties of human pancreatic tumors and in vitro constructs to mimic mechanical properties. Acta Biomater. 67, 331–340 (2018).

    Article  Google Scholar 

  182. De Stefano, P. et al. Bioprinting of matrigel scaffolds for cancer research. Polymers 13, 2026 (2021).

    Article  Google Scholar 

  183. Alave Reyes-Furrer, A. et al. Matrigel 3D bioprinting of contractile human skeletal muscle models recapitulating exercise and pharmacological responses. Commun. Biol. 4, 1183 (2021).

    Article  CAS  Google Scholar 

  184. Hedegaard, C. L. et al. Hydrodynamically guided hierarchical self-assembly of peptide–protein bioinks. Adv. Funct. Mater. https://doi.org/10.1002/adfm.201703716 (2018).

    Article  Google Scholar 

  185. Mao, S. et al. Bioprinting of in vitro tumor models for personalized cancer treatment: a review. Biofabrication 12, 042001 (2020).

    Article  CAS  Google Scholar 

  186. Murphy, R. J., Browning, A. P., Gunasingh, G., Haass, N. K. & Simpson, M. J. Designing and interpreting 4D tumour spheroid experiments. Commun. Biol. 5, 91 (2022).

    Article  CAS  Google Scholar 

  187. Meng, F. et al. 3D bioprinted in vitro metastatic models via reconstruction of tumor microenvironments. Adv. Mater. 31, 1806899 (2019).

    Article  Google Scholar 

  188. Cao, X. et al. A tumor-on-a-chip system with bioprinted blood and lymphatic vessel pair. Adv. Funct. Mater. 29, 1807173 (2019).

    Article  Google Scholar 

  189. Nashimoto, Y. et al. Vascularized cancer on a chip: the effect of perfusion on growth and drug delivery of tumor spheroid. Biomaterials 229, 119547 (2020).

    Article  CAS  Google Scholar 

  190. Chi, C.-W. et al. High-throughput tumor-on-a-chip platform to study tumor–stroma interactions and drug pharmacokinetics. Adv. Healthc. Mater. 9, 2000880 (2020).

    Article  CAS  Google Scholar 

  191. Gilardi, M. et al. The driving role of the Cdk5/Tln1/FAKS732 axis in cancer cell extravasation dissected by human vascularized microfluidic models. Biomaterials 276, 120975 (2021).

    Article  CAS  Google Scholar 

  192. Hutton, C. et al. Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity. Cancer Cell 39, 1227–1244.e20 (2021).

    Article  CAS  Google Scholar 

  193. Sahai, E. et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 20, 174–186 (2020).

    Article  CAS  Google Scholar 

  194. DePeaux, K. & Delgoffe, G. M. Metabolic barriers to cancer immunotherapy. Nat. Rev. Immunol. 21, 785–797 (2021).

    Article  CAS  Google Scholar 

  195. Waldman, A. D., Fritz, J. M. & Lenardo, M. J. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol. 20, 651–668 (2020).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the Medical Research Council (UK Regenerative Medicine Platform Acellular Smart Materials – 3D Architecture, MR/R015651/1) to A.M. and the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (grant agreement number 864253) to D.L.

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Author notes

  1. These authors contributed equally: Rodrigo Curvello, Verena Kast.

Authors and Affiliations

  1. Department of Chemical and Biological Engineering, Faculty of Engineering, Monash University, Clayton, Victoria, Australia

    Rodrigo Curvello & Daniela Loessner

  2. Leibniz Institute of Polymer Research Dresden e.V., Max Bergmann Center of Biomaterials, Dresden, Germany

    Verena Kast & Daniela Loessner

  3. Translational Medical Sciences Unit, School of Medicine, Centre for Cancer Sciences, Biodiscovery Institute, University of Nottingham, Nottingham, UK

    Paloma Ordóñez-Morán & Alvaro Mata

  4. Department of Chemical and Environmental Engineering, University of Nottingham, Nottingham, UK

    Alvaro Mata

  5. School of Pharmacy, University of Nottingham, Nottingham, UK

    Alvaro Mata

  6. Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, Victoria, Australia

    Daniela Loessner

  7. Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia

    Daniela Loessner

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Contributions

D.L. conceived the article. All authors researched the data and drafted the article. R.C., V.K. and D.L. conceived and illustrated the figures and tables. All authors made substantial contributions to the discussion of content and reviewed and edited the article.

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Correspondence to Daniela Loessner.

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Glossary

Biomimetic

Replica of the properties or elements of natural tissues or systems.

Bioscaffolds

Decellularized tissues that preserve the structural and molecular integrity of the organ-specific native extracellular matrix.

Cell-instructive

Short peptide sequences in biomaterials that present insoluble adhesion ligands and proteolytically degradable motifs and enable binding or release of soluble factors.

Desmoplastic tumour stroma

Deposition of a dense and crosslinked extracellular matrix resulting in a fibrotic tumour tissue.

Epithelial-to-mesenchymal transition

When cells become more motile, migratory and invasive through the loss of epithelial features and the gain of mesenchymal ones.

Fluid shear stress

Force created by the fluid flow parallel to a surface of a material or tissue.

Hydrogel

Water-swollen polymer network.

Interstitial flow

Movement of fluid that is transported through the extracellular matrix.

Metabolic vulnerabilities

Abnormal metabolism of cancer cells targeted by anticancer therapies.

Organoids

Self-organizing and self-renewing clusters of cells derived from tissue fragments or stem cells that mimic the functionality and behaviour of tissues.

Personalized medicines

Therapies designed for a specific patient based on its genetic or individual signature.

Scaffold

3D structure with defined geometry and mechanical properties.

Spheroids

Cell aggregates or clusters that resemble some features of tissues.

Stiffness

Resistance of a material, or tissue, to deformation and alteration of its original shape when a force is applied.

Tumorigenesis

Formation of a tumour whereby normal cells transform into cancer cells following a disrupted differentiation.

Tumour microenvironment

Dynamic network of malignant and non-malignant cells, extracellular and cell-secreted elements and soluble factors that promote tumour development, growth and metastasis.

Viscoelasticity

A time-dependent mechanical property of materials or tissues that exhibit viscous and elastic responses when forces are applied, causing temporary or permanent deformation, respectively.

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Curvello, R., Kast, V., Ordóñez-Morán, P. et al. Biomaterial-based platforms for tumour tissue engineering. Nat Rev Mater 8, 314–330 (2023). https://doi.org/10.1038/s41578-023-00535-3

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