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  • Review Article
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Hydrogels as functional components in artificial cell systems

Nature Reviews Chemistry volume 6, pages 562–578 (2022)Cite this article

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Abstract

Recent years have seen substantial efforts aimed at constructing artificial cells from various molecular components with the aim of mimicking the processes, behaviours and architectures found in biological systems. Artificial cell development ultimately aims to produce model constructs that progress our understanding of biology, as well as forming the basis for functional bio-inspired devices that can be used in fields such as therapeutic delivery, biosensing, cell therapy and bioremediation. Typically, artificial cells rely on a bilayer membrane chassis and have fluid aqueous interiors to mimic biological cells. However, a desire to more accurately replicate the gel-like properties of intracellular and extracellular biological environments has driven increasing efforts to build cell mimics based on hydrogels. This has enabled researchers to exploit some of the unique functional properties of hydrogels that have seen them deployed in fields such as tissue engineering, biomaterials and drug delivery. In this Review, we explore how hydrogels can be leveraged in the context of artificial cell development. We also discuss how hydrogels can potentially be incorporated within the next generation of artificial cells to engineer improved biological mimics and functional microsystems.

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Fig. 1: Approaches to the creation of artificial cells and the important functionalities of artificial cell systems.
Fig. 2: Chemical structures of the repeat units or primary sequences of common polymers used within hydrogel formation.
Fig. 3: Eukaryotic cell features that can be mimicked by hydrogels.
Fig. 4: The wide variety of architectures hydrogel systems have been able to form.
Fig. 5: Compartmentalization within hydrogel artificial cell systems.
Fig. 6: Hydrogels as communication tools and regulatory systems.
Fig. 7: Potential future hydrogel-inspired artificial cell structures with appropriate functionalities indicated.

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References

  1. Cho, E. & Lu, Y. Compartmentalizing cell-free systems: toward creating life-like artificial cells and beyond. ACS Synth. Biol. 9, 2881–2901 (2020).

    Article  CAS  PubMed  Google Scholar 

  2. Zhu, Y., Guo, X., Liu, J., Li, F. & Yang, D. Emerging advances of cell-free systems toward artificial cells. Small Methods 4, 2000406 (2020).

    Article  Google Scholar 

  3. Ayoubi-Joshaghani, M. H. et al. Cell-free protein synthesis: the transition from batch reactions to minimal cells and microfluidic devices. Biotechnol. Bioeng. 117, 1204–1229 (2020).

    Article  CAS  PubMed  Google Scholar 

  4. Boyd, M. A. & Kamat, N. P. Designing artificial cells towards a new generation of biosensors. Trends Biotechnol. 39, 927–939 (2021).

    Article  CAS  PubMed  Google Scholar 

  5. Laohakunakorn, N. et al. Bottom-up construction of complex biomolecular systems with cell-free synthetic biology. Front. Bioeng. Biotechnol. 8, 213 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Robinson, A. O., Venero, O. M. & Adamala, K. P. Toward synthetic life: biomimetic synthetic cell communication. Curr. Opin. Chem. Biol. 64, 165–173 (2021).

    Article  CAS  PubMed  Google Scholar 

  7. Xu, C., Hu, S. & Chen, X. Artificial cells: from basic science to applications. Mater. Today 19, 516–532 (2016).

    Article  CAS  Google Scholar 

  8. Blain, J. C. & Szostak, J. W. Progress toward synthetic cells. Annu. Rev. Biochem. 83, 615–640 (2014).

    Article  CAS  PubMed  Google Scholar 

  9. Noireaux, V., Maeda, Y. T. & Libchaber, A. Development of an artificial cell, from self-organization to computation and self-reproduction. Proc. Natl Acad. Sci. USA 108, 3473–3480 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Salehi-Reyhani, A., Ces, O. & Elani, Y. Artificial cell mimics as simplified models for the study of cell biology. Exp. Biol. Med. 242, 1309–1317 (2017).

    Article  CAS  Google Scholar 

  11. Krinsky, N. et al. Synthetic cells synthesize therapeutic proteins inside tumors. Adv. Healthc. Mater. 7, e1701163 (2018).

    Article  PubMed  CAS  Google Scholar 

  12. Khalil, A. S. & Collins, J. J. Synthetic biology: applications come of age. Nat. Rev. Genet. 11, 367–379 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Glass, J. I., Merryman, C., Wise, K. S., Hutchison, C. A. & Smith, H. O. Minimal cells-real and imagined. Cold Spring Harb. Perspect. Biol. 9, a023861 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Hutchison, C. A. et al. Design and synthesis of a minimal bacterial genome. Science 351, aad6253 (2016).

    Article  PubMed  CAS  Google Scholar 

  15. Göpfrich, K., Platzman, I. & Spatz, J. P. Mastering complexity: towards bottom-up construction of multifunctional eukaryotic synthetic cells. Trends Biotechnol. 36, 938–951 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Buddingh’, B. C. & Van Hest, J. C. M. Artificial cells: synthetic compartments with life-like functionality and adaptivity. Acc. Chem. Res. 50, 769–777 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Amy Yewdall, N., Mason, A. F. & Van Hest, J. C. M. The hallmarks of living systems: towards creating artificial cells. Interface Focus 8, 20180023 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Elani, Y., Law, R. V. & Ces, O. Vesicle-based artificial cells as chemical microreactors with spatially segregated reaction pathways. Nat. Commun. 5, 5305 (2014).

    Article  CAS  PubMed  Google Scholar 

  19. Kurokawa, C. et al. DNA cytoskeleton for stabilizing artificial cells. Proc. Natl Acad. Sci. USA 114, 7228–7233 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Deshpande, S., Wunnava, S., Hueting, D. & Dekker, C. Membrane tension–mediated growth of liposomes. Small 15, 1902898 (2019).

    Article  CAS  Google Scholar 

  21. Zhang, S. et al. Engineering motile aqueous phase-separated droplets via liposome stabilisation. Nat. Commun. 12, 1673 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Adamala, K. P., Martin-Alarcon, D. A., Guthrie-Honea, K. R. & Boyden, E. S. Engineering genetic circuit interactions within and between synthetic minimal cells. Nat. Chem. 9, 431–439 (2017).

    Article  CAS  PubMed  Google Scholar 

  23. Garamella, J., Majumder, S., Liu, A. P. & Noireaux, V. An adaptive synthetic cell based on mechanosensing, biosensing, and inducible gene circuits. ACS Synth. Biol. 8, 1913–1920 (2019).

    Article  CAS  PubMed  Google Scholar 

  24. Hindley, J. W. et al. Building a synthetic mechanosensitive signaling pathway in compartmentalized artificial cells. Proc. Natl Acad. Sci. USA 116, 16711–16716 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Rideau, E., Dimova, R., Schwille, P., Wurm, F. R. & Landfester, K. Liposomes and polymersomes: a comparative review towards cell mimicking. Chem. Soc. Rev. 47, 8572–8610 (2018).

    Article  CAS  PubMed  Google Scholar 

  26. Li, M., Huang, X., Tang, T. Y. D. & Mann, S. Synthetic cellularity based on non-lipid micro-compartments and protocell models. Curr. Opin. Chem. Biol. 22, 1–11 (2014).

    Article  PubMed  CAS  Google Scholar 

  27. Huang, X. et al. Interfacial assembly of protein-polymer nano-conjugates into stimulus-responsive biomimetic protocells. Nat. Commun. 4, 2239 (2013).

    Article  PubMed  CAS  Google Scholar 

  28. Trevors, J. T. & Pollack, G. H. Hypothesis: the origin of life in a hydrogel environment. Prog. Biophys. Mol. Biol. 89, 1–8 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Moeendarbary, E. et al. The cytoplasm of living cells behaves as a poroelastic material. Nat. Mater. 12, 253–261 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tibbitt, M. W. & Anseth, K. S. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 103, 655–663 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Peppas, N. A., Hilt, J. Z., Khademhosseini, A. & Langer, R. Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv. Mater. 18, 1345–1360 (2006).

    Article  CAS  Google Scholar 

  32. Zhang, Y. S. & Khademhosseini, A. Advances in engineering hydrogels. Science 356, eaaf3267 (2017).

    Article  Google Scholar 

  33. Gawade, P. M., Shadish, J. A., Badeau, B. A. & DeForest, C. A. Logic-based delivery of site-specifically modified proteins from environmentally responsive hydrogel biomaterials. Adv. Mater. 31, 1902462 (2019).

    Article  CAS  Google Scholar 

  34. Fares, M. M. et al. Interpenetrating network gelatin methacryloyl (GelMA) and pectin-g-PCL hydrogels with tunable properties for tissue engineering. Biomater. Sci. 6, 2938–2950 (2018).

    Article  CAS  PubMed  Google Scholar 

  35. Lou, J., Stowers, R., Nam, S., Xia, Y. & Chaudhuri, O. Stress relaxing hyaluronic acid-collagen hydrogels promote cell spreading, fiber remodeling, and focal adhesion formation in 3D cell culture. Biomaterials 154, 213–222 (2018).

    Article  CAS  PubMed  Google Scholar 

  36. Liao, M. et al. Wearable, healable, and adhesive epidermal sensors assembled from mussel-inspired conductive hybrid hydrogel framework. Adv. Funct. Mater. 27, 1703852 (2017).

    Article  CAS  Google Scholar 

  37. Gil, M. S., Thambi, T., Phan, V. H. G., Kim, S. H. & Lee, D. S. Injectable hydrogel-incorporated cancer cell-specific cisplatin releasing nanogels for targeted drug delivery. J. Mater. Chem. B 5, 7140–7152 (2017).

    Article  CAS  PubMed  Google Scholar 

  38. Li, J. & Mooney, D. J. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 1, 16071 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Knipe, J. M., Strong, L. E. & Peppas, N. A. Enzyme- and pH-responsive microencapsulated nanogels for oral delivery of siRNA to induce TNF-α knockdown in the intestine. Biomacromolecules 17, 788–797 (2016).

    Article  CAS  PubMed  Google Scholar 

  40. Ahmed, E. M. Hydrogel: preparation, characterization, and applications: a review. J. Adv. Res. 6, 105–121 (2015).

    Article  CAS  PubMed  Google Scholar 

  41. Gun’ko, V. M., Savina, I. N. & Mikhalovsky, S. V. Properties of water bound in hydrogels. Gels 3, 37 (2017).

    Article  PubMed Central  CAS  Google Scholar 

  42. Zhu, J. & Marchant, R. E. Design properties of hydrogel tissue-engineering scaffolds. Expert. Rev. Med. Device 8, 607–626 (2011).

    Article  CAS  Google Scholar 

  43. Du, X., Zhou, J., Shi, J. & Xu, B. Supramolecular hydrogelators and hydrogels: from soft matter to molecular biomaterials. Chem. Rev. 115, 13165–13307 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Janeček, E.-R. et al. Hybrid supramolecular and colloidal hydrogels that bridge multiple length scales. Angew. Chem. Int. Ed. 54, 5383–5388 (2015).

    Article  CAS  Google Scholar 

  45. Laftah, W. A., Hashim, S. & Ibrahim, A. N. Polymer hydrogels: a review. Polym. Plast. Technol. Eng. 50, 1475–1486 (2011).

    Article  CAS  Google Scholar 

  46. Shalviri, A., Liu, Q., Abdekhodaie, M. J. & Wu, X. Y. Novel modified starch-xanthan gum hydrogels for controlled drug delivery: synthesis and characterization. Carbohydr. Polym. 79, 898–907 (2010).

    Article  CAS  Google Scholar 

  47. Xiong, X. et al. Responsive DNA-based hydrogels and their applications. Macromol. Rapid Commun. 34, 1271–1283 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Fabrini, G., Minard, A., Brady, R. A., Di Antonio, M. & Di Michele, L. Cation-responsive and photocleavable hydrogels from noncanonical amphiphilic DNA nanostructures. Nano Lett. 22, 602–611 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Nöll, T., Wenderhold-Reeb, S., Schönherr, H. & Nöll, G. Pristine DNA hydrogels from biotechnologically derived plasmid DNA. Angew. Chem. Int. Ed. 56, 12004–12008 (2017).

    Article  CAS  Google Scholar 

  50. Hu, Y. et al. Bottom-up assembly of DNA–silica nanocomposites into micrometer-sized hollow spheres. Angew. Chem. Int. Ed. 58, 17269–17272 (2019).

    Article  CAS  Google Scholar 

  51. Brady, R. A., Brooks, N. J., Cicuta, P. & Di Michele, L. Crystallization of amphiphilic DNA C-stars. Nano Lett. 17, 3276–3281 (2017).

    Article  CAS  PubMed  Google Scholar 

  52. Yue, K. et al. Visible light crosslinkable human hair keratin hydrogels. Bioeng. Transl. Med. 3, 37–48 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Catoira, M. C., Fusaro, L., Di Francesco, D., Ramella, M. & Boccafoschi, F. Overview of natural hydrogels for regenerative medicine applications. J. Mater. Sci. Mater. Med. 30, 115 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Van Vlierberghe, S., Dubruel, P. & Schacht, E. Biopolymer-based hydrogels as scaffolds for tissue engineering applications: a review. Biomacromolecules 12, 1387–1408 (2011).

    Article  PubMed  CAS  Google Scholar 

  55. Rubio-Sanchez, R., Fabrini, G., Cicuta, P. & Di Michele, L. Amphiphilic DNA nanostructures for bottom-up synthetic biology. Chem. Commun. 57, 12725–12740 (2021).

    Article  CAS  Google Scholar 

  56. Kahn, J. S., Hu, Y. & Willner, I. Stimuli-responsive DNA-based hydrogels: from basic principles to applications. Acc. Chem. Res. 50, 680–690 (2017).

    Article  CAS  PubMed  Google Scholar 

  57. Morya, V., Walia, S., Mandal, B. B., Ghoroi, C. & Bhatia, D. Functional DNA based hydrogels: development properties and biological applications. ACS Biomater. Sci. Eng. 6, 6021–6035 (2020).

    Article  CAS  PubMed  Google Scholar 

  58. English, M. A. et al. Programmable CRISPR-responsive smart materials. Science 365, 780–785 (2019).

    Article  CAS  PubMed  Google Scholar 

  59. Chen, G., Sato, T., Ushida, T., Ochiai, N. & Tateishi, T. Tissue engineering of cartilage using a hybrid scaffold of synthetic polymer and collagen.Tissue Eng. 10, 323–330 (2004).

    Article  CAS  PubMed  Google Scholar 

  60. Jian, H. et al. Dipeptide self-assembled hydrogels with tunable mechanical properties and degradability for 3D bioprinting. ACS Appl. Mater. Interfaces 11, 46419–46426 (2019).

    Article  CAS  PubMed  Google Scholar 

  61. Hennink, W. E. & van Nostrum, C. F. Novel crosslinking methods to design hydrogels. Adv. Drug Deliv. Rev. 64, 223–236 (2012).

    Article  Google Scholar 

  62. Wade, R. J., Bassin, E. J., Rodell, C. B. & Burdick, J. A. Protease-degradable electrospun fibrous hydrogels. Nat. Commun. 6, 6639 (2015).

    Article  CAS  PubMed  Google Scholar 

  63. Crivello, J. V. & Reichmanis, E. Photopolymer materials and processes for advanced technologies. Chem. Mater. 26, 533–548 (2014).

    Article  CAS  Google Scholar 

  64. Braun, D. Origins and development of initiation of free radical polymerization processes. Int. J. Polym. Sci. 2009, 893234 (2009).

    Article  CAS  Google Scholar 

  65. Sarac, A. S. Redox polymerization. Prog. Polym. Sci. 24, 1149–1204 (1999).

    Article  CAS  Google Scholar 

  66. Nimmo, C. M., Owen, S. C. & Shoichet, M. S. Diels-Alder click cross-linked hyaluronic acid hydrogels for tissue engineering. Biomacromolecules 12, 824–830 (2011).

    Article  CAS  PubMed  Google Scholar 

  67. Hiemstra, C., van der Aa, L. J., Zhong, Z., Dijkstra, P. J. & Feijen, J. Rapidly in situ-forming degradable hydrogels from dextram triols through Michael addition. Biomacromolecules 8, 1548–1556 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Javvaji, V., Baradwaj, A. G., Payne, G. F. & Raghavan, S. R. Light-activated ionic gelation of common biopolymers. Langmuir 27, 12591–12596 (2011).

    Article  CAS  PubMed  Google Scholar 

  69. Hu, W., Wang, Z., Xiao, Y., Zhang, S. & Wang, J. Advances in crosslinking strategies of biomedical hydrogels. Biomater. Sci. 7, 843–855 (2019).

    Article  CAS  PubMed  Google Scholar 

  70. Zhong, M. et al. Self-healable, tough and highly stretchable ionic nanocomposite physical hydrogels. Soft Matter 11, 4235–4241 (2015).

    Article  CAS  PubMed  Google Scholar 

  71. Koetting, M. C., Peters, J. T., Steichen, S. D. & Peppas, N. A. Stimulus-responsive hydrogels: theory, modern advances, and applications. Mater. Sci. Eng. R. Rep. 93, 1–49 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Chatterjee, S., Hui, P. C. L. & Kan, C. W. Thermoresponsive hydrogels and their biomedical applications: special insight into their applications in textile based transdermal therapy. Polymers 10, 480 (2018).

    Article  PubMed Central  CAS  Google Scholar 

  73. Drozdov, A. D. & Sommer-Larsen, P. Swelling of thermo-responsive gels under hydrostatic pressure. Meccanica 51, 1419–1434 (2016).

    Article  Google Scholar 

  74. Gupta, P., Vermani, K. & Garg, S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug. Discov. Today 7, 569–579 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Xiang, T., Lu, T., Zhao, W. F. & Zhao, C. S. Ionic-strength responsive Zwitterionic copolymer hydrogels with tunable swelling and adsorption behaviors. Langmuir 35, 1146–1155 (2019).

    Article  CAS  PubMed  Google Scholar 

  76. Rosales, A. M., Vega, S. L., DelRio, F. W., Burdick, J. A. & Anseth, K. S. Hydrogels with reversible mechanics to probe dynamic cell microenvironments. Angew. Chem. Int. Ed. 56, 12132–12136 (2017).

    Article  CAS  Google Scholar 

  77. Takashima, Y. et al. Expansion-contraction of photoresponsive artificial muscle regulated by host-guest interactions. Nat. Commun. 3, 1270 (2012).

    Article  PubMed  CAS  Google Scholar 

  78. Kim, S. J., Park, S. J., Kim, I. Y., Shin, M. S. & Kim, S. I. Electric stimuli responses to poly(vinyl alcohol)/chitosan interpenetrating polymer network hydrogel in NaCl solutions. J. Appl. Polym. Sci. 86, 2285–2289 (2002).

    Article  CAS  Google Scholar 

  79. Wu, C. H. et al. Ultrasound-responsive NIPAM-based hydrogels with tunable profile of controlled release of large molecules. Ultrasonics 83, 157–163 (2018).

    Article  CAS  PubMed  Google Scholar 

  80. Emi, T. T. et al. Pulsatile chemotherapeutic delivery profiles using magnetically responsive hydrogels. ACS Biomater. Sci. Eng. 4, 2412–2423 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Orlov, Y., Xu, X. & Maurer, G. Equilibrium swelling of N-isopropyl acrylamide based ionic hydrogels in aqueous solutions of organic solvents: comparison of experiment with theory. Fluid Phase Equilib. 249, 6–16 (2006).

    Article  CAS  Google Scholar 

  82. Matsuda, T., Kawakami, R., Namba, R., Nakajima, T. & Gong, J. P. Mechanoresponsive self-growing hydrogels inspired by muscle training. Science 363, 504–508 (2019).

    Article  CAS  PubMed  Google Scholar 

  83. Zhou, Y. & Jin, L. Hydrolysis-induced large swelling of polyacrylamide hydrogels. Soft Matter 16, 5740–5749 (2020).

    Article  CAS  PubMed  Google Scholar 

  84. Vemula, P. K., Cruikshank, G. A., Karp, J. M. & John, G. Self-assembled prodrugs: an enzymatically triggered drug-delivery platform. Biomaterials 30, 383–393 (2009).

    Article  CAS  PubMed  Google Scholar 

  85. Nakahata, M., Takashima, Y., Yamaguchi, H. & Harada, A. Redox-responsive self-healing materials formed from host-guest polymers. Nat. Commun. 2, 511 (2011).

    Article  PubMed  CAS  Google Scholar 

  86. Gaharwar, A. K., Peppas, N. A. & Khademhosseini, A. Nanocomposite hydrogels for biomedical applications. Biotechnol. Bioeng. 111, 441–453 (2014).

    Article  CAS  PubMed  Google Scholar 

  87. de Almeida, P. et al. Cytoskeletal stiffening in synthetic hydrogels. Nat. Commun. 10, 609 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Beebe, D. J. et al. Functional hydrogel structures for autonomous flow control inside microfluidic channels. Nature 404, 588–590 (2000).

    Article  CAS  PubMed  Google Scholar 

  89. Jiang, Z. et al. Strong, self‐healable, and recyclable visible‐light‐responsive hydrogel actuators. Angew. Chem. Int. Ed. 59, 7049–7056 (2020).

    Article  CAS  Google Scholar 

  90. Guiseppi-Elie, A., Brahim, S. I. & Narinesingh, D. A chemically synthesized artificial pancreas: release of insulin from glucose-responsive hydrogels. Adv. Mater. 14, 743–746 (2002).

    Article  CAS  Google Scholar 

  91. Fels, J., Orlov, S. N. & Grygorczyk, R. The hydrogel nature of mammalian cytoplasm contributes to osmosensing and extracellular pH sensing. Biophys. J. 96, 4276–4285 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Niederholtmeyer, H., Chaggan, C. & Devaraj, N. K. Communication and quorum sensing in non-living mimics of eukaryotic cells. Nat. Commun. 9, 5027 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Peppas, N. A., Bures, P., Leobandung, W. & Ichikawa, H. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 50, 27–46 (2000).

    Article  CAS  PubMed  Google Scholar 

  95. Spitzer, J. J. & Poolman, B. Electrochemical structure of the crowded cytoplasm. Trends Biochem. Sci. 30, 536–541 (2005).

    Article  CAS  PubMed  Google Scholar 

  96. Aumailley, M. & Gayraud, B. Structure and biological activity of the extracellular matrix. J. Mol. Med. 76, 253–265 (1998).

    Article  CAS  PubMed  Google Scholar 

  97. Newport, J. W. & Forbes, D. J. The nucleus: structure, function, and dynamics. Annu. Rev. Biochem. 56, 535–565 (1987).

    Article  CAS  PubMed  Google Scholar 

  98. Rowat, A. C., Lammerding, J., Herrmann, H. & Aebi, U. Towards an integrated understanding of the structure and mechanics of the cell nucleus. BioEssays 30, 226–236 (2008).

    Article  PubMed  Google Scholar 

  99. Misteli, T. Physiological importance of RNA and protein mobility in the cell nucleus. Histochem. Cell Biol. 129, 5–11 (2008).

    Article  CAS  PubMed  Google Scholar 

  100. Ghosh, S., Chattoraj, S., Mondal, T. & Bhattacharyya, K. Dynamics in cytoplasm, nucleus, and lipid droplet of a live CHO cell: time-resolved confocal microscopy. Langmuir 29, 7975–7982 (2013).

    Article  CAS  PubMed  Google Scholar 

  101. Aufinger, L. & Simmel, F. C. Artificial gel-based organelles for spatial organization of cell-free gene expression reactions. Angew. Chem. Int. Ed. 57, 17245–17248 (2018).

    Article  CAS  Google Scholar 

  102. Yue, B. Biology of the extracellular matrix: an overview. J. Glaucoma 23, S20–S23 (2014).

    Article  PubMed  Google Scholar 

  103. Vining, K. H. & Mooney, D. J. Mechanical forces direct stem cell behaviour in development and regeneration. Nat. Rev. Mol. Cell Biol. 18, 728–742 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Giobbe, G. G. et al. Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture. Nat. Commun. 10, 5658 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Cox, T. R. & Erler, J. T. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis. Model. Mech. 4, 165–178 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. 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. Nat. Mater. 7, 816–823 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Khan, F., Tare, R. S., Oreffo, R. O. C. & Bradley, M. Versatile biocompatible polymer hydrogels: scaffolds for cell growth. Angew. Chem. Int. Ed. 48, 978–982 (2009).

    Article  CAS  Google Scholar 

  108. Liu, H. et al. Advances in hydrogels in organoids and organs-on-a-chip. Adv. Mater. 31, 1902042 (2019).

    Article  CAS  Google Scholar 

  109. Deller, R. C. et al. Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation. Nat. Commun. 10, 1887 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Fletcher, D. A. & Mullins, R. D. Cell mechanics and the cytoskeleton. Nature 463, 485–492 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Hohmann, T. & Dehghani, F. The cytoskeleton — a complex interacting meshwork. Cells 8, 362 (2019).

    Article  CAS  PubMed Central  Google Scholar 

  112. Bashirzadeh, Y. & Liu, A. P. Encapsulation of the cytoskeleton: towards mimicking the mechanics of a cell. Soft Matter 15, 8425–8436 (2019).

    Article  CAS  PubMed  Google Scholar 

  113. Tank, D. W., Wu, E. S. & Webb, W. W. Enhanced molecular diffusibility in muscle membrane blebs: release of lateral constraints. J. Cell Biol. 92, 207–212 (1982).

    Article  CAS  PubMed  Google Scholar 

  114. Potma, E. O. et al. Reduced protein diffusion rate by cytoskeleton in vegetative and polarized Dictyostelium cells. Biophys. J. 81, 2010–2019 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Garamella, J., Regan, K., Aguirre, G., McGorty, R. J. & Robertson-Anderson, R. M. Anomalous and heterogeneous DNA transport in biomimetic cytoskeleton networks. Soft Matter 16, 6344–6353 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Sano, K. I. et al. Self-repairing filamentous actin hydrogel with hierarchical structure. Biomacromolecules 12, 4173–4177 (2011).

    Article  CAS  PubMed  Google Scholar 

  117. Litschel, T. et al. Reconstitution of contractile actomyosin rings in vesicles. Nat. Commun. 12, 2254 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Knoff, D. S., Szczublewski, H., Altamirano, D., Fajardo Cortes, K. A. & Kim, M. Cytoskeleton-inspired artificial protein design to enhance polymer network elasticity. Macromolecules 53, 3464–3471 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Luby-Phelps, K. The physical chemistry of cytoplasm and its influence on cell function: an update. Mol. Biol. Cell 24, 2593–2596 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Mastro, A. M., Babich, M. A., Taylor, W. D. & Keith, A. D. Diffusion of a small molecule in the cytoplasm of mammalian cells. Proc. Natl Acad. Sci. USA 81, 3414–3418 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Cameron, I. L. et al. Maintenance of ions, proteins and water in lens fiber cells before and after treatment with non-ionic detergents. Cell Biol. Int. 20, 127–137 (1996).

    Article  CAS  PubMed  Google Scholar 

  122. Elliott, G. F., Goodfellow, J. M. & Woolgar, A. E. Swelling studies of bovine corneal stroma without bounding membranes. J. Physiol. 298, 453–470 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Grygorczyk, R., Boudreault, F., Platonova, A. & Orlov, S. N. Salt and osmosensing: role of cytoplasmic hydrogel. Pflug. Arch. Eur. J. Physiol. 467, 475–487 (2015).

    Article  CAS  Google Scholar 

  124. Toprakcioglu, Z., Challa, P. K., Morse, D. B. & Knowles, T. Attoliter protein nanogels from droplet nanofluidics for intracellular delivery. Sci. Adv. 6, eaay7952 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Tanaka, T. & Fillmore, D. J. Kinetics of swelling of gels. J. Chem. Phys. 70, 1214–1218 (1979).

    Article  CAS  Google Scholar 

  126. Ahiabu, A. & Serpe, M. J. Rapidly responding pH- and temperature-responsive poly (N-isopropylacrylamide)-based microgels and assemblies. ACS Omega 2, 1769–1777 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Varga, I., Szalai, I., Mészaros, R. & Gilányi, T. Pulsating pH-responsive nanogels. J. Phys. Chem. B 110, 20297–20301 (2006).

    Article  CAS  PubMed  Google Scholar 

  128. Parisi, O. I. et al. Controlled release of sunitinib in targeted cancer therapy: smart magnetically responsive hydrogels as restricted access materials. RSC Adv. 5, 65308–65315 (2015).

    Article  CAS  Google Scholar 

  129. Trantidou, T. et al. Engineering compartmentalized biomimetic micro- and nanocontainers. ACS Nano 11, 6549–6565 (2017).

    Article  CAS  PubMed  Google Scholar 

  130. Margolis, L. & Sadovsky, Y. The biology of extracellular vesicles: the known unknowns. PLoS Biol. 17, e3000363 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Milo, R. & Phillips, R. Cell Biology by the Numbers (Garland Science, 2015).

  132. Sato, Y. & Takinoue, M. Capsule-like DNA hydrogels with patterns formed by lateral phase separation of DNA nanostructures. JACS Au 2, 159–168 (2022).

    Article  CAS  PubMed  Google Scholar 

  133. Saunders, B. R. & Vincent, B. Microgel particles as model colloids: theory, properties and applications. Adv. Colloid Interface Sci. 80, 1–25 (1999).

    Article  CAS  Google Scholar 

  134. Downey, J. S., Frank, R. S., Li, W. H. & Stöver, H. D. H. Growth mechanism of poly(divinylbenzene) microspheres in precipitation polymerization. Macromolecules 32, 2838–2844 (1999).

    Article  CAS  Google Scholar 

  135. Hu, X., Tong, Z. & Lyon, L. A. Multicompartment core/shell microgels. J. Am. Chem. Soc. 132, 11470–11472 (2010).

    Article  CAS  PubMed  Google Scholar 

  136. Städler, B. et al. Polymer hydrogel capsules: en route toward synthetic cellular systems. Nanoscale 1, 68–73 (2009).

    Article  PubMed  CAS  Google Scholar 

  137. Kasahara, Y., Sato, Y., Masukawa, M. K., Okuda, Y. & Takinoue, M. Photolithographic shape control of DNA hydrogels by photo-activated self-assembly of DNA nanostructures. APL Bioeng. 4, 016109 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Dendukuri, D., Pregibon, D. C., Collins, J., Hatton, T. A. & Doyle, P. S. Continuous-flow lithography for high-throughput microparticle synthesis. Nat. Mater. 5, 365–369 (2006).

    Article  CAS  PubMed  Google Scholar 

  139. Cangialosi, A. et al. DNA sequence–directed shape change of photopatterned hydrogels via high-degree swelling. Science 357, 1126–1130 (2017).

    Article  CAS  PubMed  Google Scholar 

  140. Chen, K. et al. Low modulus biomimetic microgel particles with high loading of hemoglobin. Biomacromolecules 13, 2748–2759 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Kilian, K. A., Bugarija, B., Lahn, B. T. & Mrksich, M. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc. Natl Acad. Sci. USA 107, 4872–4877 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Muir, V. G., Qazi, T. H., Shan, J., Groll, J. & Burdick, J. A. Influence of microgel fabrication technique on granular hydrogel properties. ACS Biomater. Sci. Eng. 7, 4269–4281 (2021).

    Article  CAS  PubMed  Google Scholar 

  143. Lee, S., Che, B., Tai, M., Li, W. & Kim, S. H. Designing semipermeable hydrogel shells with controlled thickness through internal osmosis in triple-emulsion droplets. Adv. Funct. Mater. 31, 2105477 (2021).

    Article  CAS  Google Scholar 

  144. Chen, M., Bolognesi, G. & Vladisavljević, G. T. Crosslinking strategies for the microfluidic production of microgels. Molecules 26, 3752 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Wan, J. Microfluidic-based synthesis of hydrogel particles for cell microencapsulation and cell-based drug delivery. Polymers 4, 1084–1108 (2012).

    Article  CAS  Google Scholar 

  146. Utech, S. et al. Microfluidic generation of monodisperse, structurally homogeneous alginate microgels for cell encapsulation and 3D cell culture. Adv. Healthc. Mater. 4, 1628–1633 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Liao, Q. Q. et al. Biocompatible fabrication of cell-laden calcium alginate microbeads using microfluidic double flow-focusing device. Sens. Actuators A Phys. 279, 313–320 (2018).

    Article  CAS  Google Scholar 

  148. Akbari, S. & Pirbodaghi, T. Microfluidic encapsulation of cells in alginate particles via an improved internal gelation approach. Microfluid. Nanofluid. 16, 773–777 (2014).

    Article  CAS  Google Scholar 

  149. Huang, H. et al. Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture. Lab Chip 17, 1913–1932 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Zhao, Z. et al. Injectable microfluidic hydrogel microspheres for cell and drug delivery. Adv. Funct. Mater. 31, 2103339 (2021).

    Article  CAS  Google Scholar 

  151. Chu, J. O. et al. Cell-inspired hydrogel microcapsules with a thin oil layer for enhanced retention of highly reactive antioxidants. ACS Appl. Mater. Interfaces 14, 2597–2604 (2022).

    Article  CAS  PubMed  Google Scholar 

  152. Choi, C. H. et al. One-step generation of cell-laden microgels using double emulsion drops with a sacrificial ultra-thin oil shell. Lab Chip 16, 1549–1555 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Baxani, D. K. et al. Bilayer networks within a hydrogel shell: a robust chassis for artificial cells and a platform for membrane studies. Angew. Chem. Int. Ed. 55, 14240–14245 (2016).

    Article  CAS  Google Scholar 

  154. Thiele, J. et al. DNA-functionalized hydrogels for confined membrane-free in vitro transcription/translation. Lab Chip 14, 2651–2656 (2014).

    Article  CAS  PubMed  Google Scholar 

  155. He, F. et al. Controllable multicompartmental capsules with distinct cores and shells for synergistic release. ACS Appl. Mater. Interfaces 8, 8743–8754 (2016).

    Article  CAS  PubMed  Google Scholar 

  156. Xu, Y. et al. Liquid–liquid phase-separated systems from reversible gel–sol transition of protein microgels. Adv. Mater. 33, e2008670 (2021).

    Article  PubMed  CAS  Google Scholar 

  157. Martino, C., Lee, T. Y., Kim, S. H. & DeMello, A. J. Microfluidic generation of PEG-b-PLA polymersomes containing alginate-based core hydrogel. Biomicrofluidics 9, 024101 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Van Swaay, D. & Demello, A. Microfluidic methods for forming liposomes. Lab Chip 13, 752–767 (2013).

    Article  PubMed  CAS  Google Scholar 

  159. Trantidou, T., Friddin, M. S., Salehi-Reyhani, A., Ces, O. & Elani, Y. Droplet microfluidics for the construction of compartmentalised model membranes. Lab Chip 18, 2488–2509 (2018).

    Article  CAS  PubMed  Google Scholar 

  160. Ugrinic, M., DeMello, A. & Tang, T. Y. D. Microfluidic tools for bottom-up synthetic cellularity. Chem 5, 1727–1742 (2019).

    Article  CAS  Google Scholar 

  161. Hong, J. S. et al. Microfluidic directed self-assembly of liposome-hydrogel hybrid nanoparticles. Langmuir 26, 11581–11588 (2010).

    Article  CAS  PubMed  Google Scholar 

  162. Peruzzi, J., Gutierrez, M. G., Mansfield, K. & Malmstadt, N. Dynamics of hydrogel-assisted giant unilamellar vesicle formation from unsaturated lipid systems. Langmuir 32, 12702–12709 (2016).

    Article  CAS  PubMed  Google Scholar 

  163. Weinberger, A. et al. Gel-assisted formation of giant unilamellar vesicles. Biophys. J. 105, 154–164 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Parigoris, E. et al. Facile generation of giant unilamellar vesicles using polyacrylamide gels. Sci. Rep. 10, 4824 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Huang, N., Guan, Y., Zhu, X. X. & Zhang, Y. Swelling kinetics of microgels embedded in a polyacrylamide hydrogel matrix. ChemPhysChem 15, 1785–1792 (2014).

    Article  CAS  PubMed  Google Scholar 

  166. Caliari, S. R. & Burdick, J. A. A practical guide to hydrogels for cell culture. Nat. Methods 13, 405–414 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Schmidt, S. et al. Adhesion and mechanical properties of PNIPAM microgel films and their potential use as switchable cell culture substrates. Adv. Funct. Mater. 20, 3235–3243 (2010).

    Article  CAS  Google Scholar 

  168. Zhang, J. et al. Micropatterned soft hydrogels to study the interplay of receptors and forces in T cell activation. Acta Biomater. 119, 234–246 (2021).

    Article  CAS  PubMed  Google Scholar 

  169. Kamperman, T., Karperien, M., Le Gac, S. & Leijten, J. Single-cell microgels: technology, challenges, and applications. Trends Biotechnol. 36, 850–865 (2018).

    Article  CAS  PubMed  Google Scholar 

  170. Li, J., Wu, C., Chu, P. K. & Gelinsky, M. 3D printing of hydrogels: rational design strategies and emerging biomedical applications. Mater. Sci. Eng. R. Rep. 140, 100543 (2020).

    Article  Google Scholar 

  171. Mulakkal, M. C., Trask, R. S., Ting, V. P. & Seddon, A. M. Responsive cellulose-hydrogel composite ink for 4D printing. Mater. Des. 160, 108–118 (2018).

    Article  CAS  Google Scholar 

  172. Müller, J., Jäkel, A. C., Schwarz, D., Aufinger, L. & Simmel, F. C. Programming diffusion and localization of DNA signals in 3D-printed DNA-functionalized hydrogels. Small 16, 2001815 (2020).

    Article  CAS  Google Scholar 

  173. Shiblee, M. N. I., Ahmed, K., Khosla, A., Kawakami, M. & Furukawa, H. 3D printing of shape memory hydrogels with tunable mechanical properties. Soft Matter 14, 7809–7817 (2018).

    Article  CAS  PubMed  Google Scholar 

  174. Sydney Gladman, A., Matsumoto, E. A., Nuzzo, R. G., Mahadevan, L. & Lewis, J. A. Biomimetic 4D printing. Nat. Mater. 15, 413–418 (2016).

    Article  CAS  PubMed  Google Scholar 

  175. Yang, C. et al. Hydrogel walkers with electro-driven motility for cargo transport. Sci. Rep. 5, 13622 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Xu, Z., Xu, Z. & Fu, J. Programmable and reversible 3D-/4D-shape-morphing hydrogels with precisely defined ion coordination. ACS Appl. Mater. Interfaces 12, 26476–26484 (2020).

    Article  CAS  PubMed  Google Scholar 

  177. Tan, H. et al. Heterogeneous multi-compartmental hydrogel particles as synthetic cells for incompatible tandem reactions. Nat. Commun. 8, 663 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  178. Rollié, S., Mangold, M. & Sundmacher, K. Designing biological systems: systems engineering meets synthetic biology. Chem. Eng. Sci. 69, 1–29 (2012).

    Article  CAS  Google Scholar 

  179. Hatori, M. N., Kim, S. C. & Abate, A. R. Particle-templated emulsification for microfluidics-free digital biology. Anal. Chem. 90, 9813–9820 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Fischlechner, M. et al. Evolution of enzyme catalysts caged in biomimetic gel-shell beads. Nat. Chem. 6, 791–796 (2014).

    Article  CAS  PubMed  Google Scholar 

  181. Jäckel, C. & Hilvert, D. Biocatalysts by evolution. Curr. Opin. Biotechnol. 21, 753–759 (2010).

    Article  PubMed  CAS  Google Scholar 

  182. Lin, W. et al. Cartilage-inspired, lipid-based boundary-lubricated hydrogels. Science 370, 335–338 (2020).

    Article  CAS  PubMed  Google Scholar 

  183. Bayley, H. et al. Droplet interface bilayers. Mol. Biosyst. 4, 1191–1208 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Elani, Y., Solvas, X. C. I., Edel, J. B., Law, R. V. & Ces, O. Microfluidic generation of encapsulated droplet interface bilayer networks (multisomes) and their use as cell-like reactors. Chem. Commun. 52, 5961–5964 (2016).

    Article  CAS  Google Scholar 

  185. Strutt, R. et al. Activating mechanosensitive channels embedded in droplet interface bilayers using membrane asymmetry. Chem. Sci. 12, 2138–2145 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Funakoshi, K., Suzuki, H. & Takeuchi, S. Lipid bilayer formation by contacting monolayers in a microfluidic device for membrane protein analysis. Anal. Chem. 78, 8169–8174 (2006).

    Article  CAS  PubMed  Google Scholar 

  187. Allen-Benton, M., Findlay, H. E. & Booth, P. J. Probing membrane protein properties using droplet interface bilayers. Exp. Biol. Med. 244, 709–720 (2019).

    Article  CAS  Google Scholar 

  188. Li, J. et al. Formation of polarized, functional artificial cells from compartmentalized droplet networks and nanomaterials, using one-step, dual-material 3D-printed microfluidics. Adv. Sci. 7, 1901719 (2020).

    Article  CAS  Google Scholar 

  189. Bayoumi, M., Bayley, H., Maglia, G. & Sapra, K. T. Multi-compartment encapsulation of communicating droplets and droplet networks in hydrogel as a model for artificial cells. Sci. Rep. 7, 45167 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Downs, F. G. et al. Multi-responsive hydrogel structures from patterned droplet networks. Nat. Chem. 12, 363–371 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Hoskin, C. E. G., Schild, V. R., Vinals, J. & Bayley, H. Parallel transmission in a synthetic nerve. Nat. Chem. 14, 650–657 (2022).

    Article  CAS  PubMed  Google Scholar 

  192. Jensen, B. E. B. et al. Lipogels: surface-adherent composite hydrogels assembled from poly(vinyl alcohol) and liposomes. Nanoscale 5, 6758–6766 (2013).

    Article  CAS  PubMed  Google Scholar 

  193. Li, R. et al. Injectable and in situ-formable thiolated chitosan-coated liposomal hydrogels as curcumin carriers for prevention of in vivo breast cancer recurrence. ACS Appl. Mater. Interfaces 12, 17936–17948 (2020).

    Article  CAS  PubMed  Google Scholar 

  194. Cheng, R. et al. Mechanically enhanced lipo-hydrogel with controlled release of multi-type drugs for bone regeneration. Appl. Mater. Today 12, 294–308 (2018).

    Article  Google Scholar 

  195. Liu, J. et al. Hydrogel-immobilized coacervate droplets as modular microreactor assemblies. Angew. Chem. Int. Ed. 59, 6853–6859 (2020).

    Article  CAS  Google Scholar 

  196. Wang, H. et al. One-step generation of aqueous-droplet-filled hydrogel fibers as organoid carriers using an all-in-water microfluidic system. ACS Appl. Mater. Interfaces 13, 3199–3208 (2021).

    Article  CAS  PubMed  Google Scholar 

  197. Zhu, C., Itel, F., Chandrawati, R., Han, X. & Städler, B. Multicompartmentalized microreactors containing nuclei and catalase-loaded liposomes. Biomacromolecules 19, 4379–4385 (2018).

    Article  CAS  PubMed  Google Scholar 

  198. Guo, S. et al. Engineered living materials based on adhesin-mediated trapping of programmable cells. ACS Synth. Biol. 9, 475–485 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Ahn, S. H., Rath, M., Tsao, C. Y., Bentley, W. E. & Raghavan, S. R. Single-step synthesis of alginate microgels enveloped with a covalent polymeric shell: a simple way to protect encapsulated cells. ACS Appl. Mater. Interfaces 13, 18432–18442 (2021).

    Article  CAS  PubMed  Google Scholar 

  200. Walczak, M. et al. Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria entrapment. Nat. Commun. 12, 4743 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Westensee, I. N. et al. Mitochondria encapsulation in hydrogel-based artificial cells as ATP producing subunits. Small 17, 2007959 (2021).

    Article  CAS  Google Scholar 

  202. Eun, Y. J., Utada, A. S., Copeland, M. F., Takeuchi, S. & Weibel, D. B. Encapsulating bacteria in agarose microparticles using microfluidics for high-throughput cell analysis and isolation. ACS Chem. Biol. 6, 260–266 (2011).

    Article  CAS  PubMed  Google Scholar 

  203. Tang, T. C. et al. Hydrogel-based biocontainment of bacteria for continuous sensing and computation. Nat. Chem. Biol. 17, 724–731 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Suzuka, J. et al. Rapid reprogramming of tumour cells into cancer stem cells on double-network hydrogels. Nat. Biomed. Eng. 5, 914–925 (2021).

    Article  CAS  PubMed  Google Scholar 

  205. Qian, X., Westensee, I. N., Fernandes, C. C. & Städler, B. Enzyme mimic facilitated artificial cell to mammalian cell signal transfer. Angew. Chem. Int. Ed. 60, 18704–18711 (2021).

    Article  CAS  Google Scholar 

  206. Juthani, N. & Doyle, P. S. A platform for multiplexed colorimetric microRNA detection using shape-encoded hydrogel particles. Analyst 145, 5134–5140 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Zeng, R., Huang, Z., Wang, Y. & Tang, D. Enzyme-encapsulated DNA hydrogel for highly efficient electrochemical sensing glucose. ChemElectroChem 7, 1537–1541 (2020).

    Article  CAS  Google Scholar 

  208. Song, J. et al. Self-assembly of a magnetic DNA hydrogel as a new biomaterial for enzyme encapsulation with enhanced activity and stability. Chem. Commun. 55, 2449–2452 (2019).

    Article  CAS  Google Scholar 

  209. Shin, D. S. et al. Synthesis of microgel sensors for spatial and temporal monitoring of protease activity. ACS Biomater. Sci. Eng. 4, 378–387 (2018).

    Article  CAS  PubMed  Google Scholar 

  210. Lee, K. et al. Multifunctional DNA nanogels for aptamer-based targeted delivery and stimuli-triggered release of cancer therapeutics. Macromol. Rapid Commun. 42, 2000457 (2021).

    Article  CAS  Google Scholar 

  211. Zhang, H. et al. Cancer biomarker-triggered disintegrable DNA nanogels for intelligent drug delivery. Nano Lett. 20, 8399–8407 (2020).

    Article  CAS  PubMed  Google Scholar 

  212. Abdel-Fatah, T. M. A. et al. Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer. Mol. Oncol. 8, 1326–1338 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Ma, J. et al. Liposomes-camouflaged redox-responsive nanogels to resolve the dilemma between extracellular stability and intracellular drug release. Macromol. Biosci. 18, 1800049 (2018).

    Article  CAS  Google Scholar 

  214. Hu, C. M. J. et al. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc. Natl Acad. Sci. USA 108, 10980–10985 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Saleem, Q., Zhang, Z., Gradinaru, C. C. & MacDonald, P. M. Liposome-coated hydrogel spheres: delivery vehicles with tandem release from distinct compartments. Langmuir 29, 14603–14612 (2013).

    Article  CAS  PubMed  Google Scholar 

  216. Hanuš, J., Ullrich, M., Dohnal, J., Singh, M. & Štěpánek, F. Remotely controlled diffusion from magnetic liposome microgels. Langmuir 29, 4381–4387 (2013).

    Article  PubMed  CAS  Google Scholar 

  217. Hong, Y. J., Lee, H. Y. & Kim, J. C. Alginate beads containing pH-sensitive liposomes and glucose oxidase: glucose-sensitive release. Colloid Polym. Sci. 287, 1207–1214 (2009).

    Article  CAS  Google Scholar 

  218. Volpatti, L. R. et al. Microgel encapsulated nanoparticles for glucose-responsive insulin delivery. Biomaterials 267, 120458 (2021).

    Article  CAS  PubMed  Google Scholar 

  219. Vader, P., Mol, E. A., Pasterkamp, G. & Schiffelers, R. M. Extracellular vesicles for drug delivery. Adv. Drug Deliv. Rev. 106, 148–156 (2016).

    Article  CAS  PubMed  Google Scholar 

  220. Fuhrmann, G. et al. Engineering extracellular vesicles with the tools of enzyme prodrug therapy. Adv. Mater. 30, 1706616 (2018).

    Article  CAS  Google Scholar 

  221. Zhang, H., Koens, L., Lauga, E., Mourran, A. & Möller, M. A light-driven microgel rotor. Small 15, 1903379 (2019).

    Article  CAS  Google Scholar 

  222. Alvarez, L. et al. Reconfigurable artificial microswimmers with internal feedback. Nat. Commun. 12, 4762 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Gao, N. et al. Chemical-mediated translocation in protocell-based microactuators. Nat. Chem. 13, 868–879 (2021).

    Article  CAS  PubMed  Google Scholar 

  224. Park, N., Um, S. H., Funabashi, H., Xu, J. & Luo, D. A cell-free protein-producing gel. Nat. Mater. 8, 432–437 (2009).

    Article  CAS  PubMed  Google Scholar 

  225. Whitfield, C. J. et al. Cell-free protein synthesis in hydrogel materials. Chem. Commun. 56, 7108–7111 (2020).

    Article  CAS  Google Scholar 

  226. Benítez-Mateos, A. I. et al. Microcompartmentalized cell-free protein synthesis in hydrogel μ-channels. ACS Synth. Biol. 9, 2971–2978 (2020).

    Article  PubMed  CAS  Google Scholar 

  227. Park, N. et al. High-yield cell-free protein production from P-gel. Nat. Protoc. 4, 1759–1770 (2009).

    Article  CAS  PubMed  Google Scholar 

  228. Lee, K. H., Lee, K. Y., Byun, J. Y., Kim, B. G. & Kim, D. M. On-bead expression of recombinant proteins in an agarose gel matrix coated on a glass slide. Lab Chip 12, 1605–1610 (2012).

    Article  CAS  PubMed  Google Scholar 

  229. Byun, J. Y., Lee, K. H., Lee, K. Y., Kim, M. G. & Kim, D. M. In-gel expression and in situ immobilization of proteins for generation of three dimensional protein arrays in a hydrogel matrix. Lab Chip 13, 886–891 (2013).

    Article  CAS  PubMed  Google Scholar 

  230. Ouyang, X., Zhou, X., Lai, S. N., Liu, Q. & Zheng, B. Immobilization of proteins of cell extract to hydrogel networks enhances the longevity of cell-free protein synthesis and supports gene networks. ACS Synth. Biol. 10, 749–755 (2021).

    Article  CAS  PubMed  Google Scholar 

  231. Vibhute, M. A. et al. Transcription and translation in cytomimetic protocells perform most efficiently at distinct macromolecular crowding conditions. ACS Synth. Biol. 9, 2797–2807 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Yang, D. et al. Enhanced transcription and translation in clay hydrogel and implications for early life evolution. Sci. Rep. 3, 3165 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  233. Hanczyc, M. M., Fujikawa, S. M. & Szostak, J. W. Experimental models of primitive cellular compartments: encapsulation, growth, and division. Science 302, 618–622 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Kahn, J. S. et al. DNA microgels as a platform for cell-free protein expression and display. Biomacromolecules 17, 2019–2026 (2016).

    Article  CAS  PubMed  Google Scholar 

  235. Jiao, Y., Liu, Y., Luo, D., Huck, W. T. S. & Yang, D. Microfluidic-assisted fabrication of clay microgels for cell-free protein synthesis. ACS Appl. Mater. Interfaces 10, 29308–29313 (2018).

    Article  CAS  PubMed  Google Scholar 

  236. Lai, S. N. et al. Artificial cells capable of long-lived protein synthesis by using aptamer grafted polymer hydrogel. ACS Synth. Biol. 9, 76–83 (2020).

    Article  CAS  PubMed  Google Scholar 

  237. Zhou, X., Wu, H., Cui, M., Lai, S. N. & Zheng, B. Long-lived protein expression in hydrogel particles: towards artificial cells. Chem. Sci. 9, 4275–4279 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Cui, J. et al. A PEGDA/DNA hybrid hydrogel for cell-free protein synthesis. Front. Chem. 8, 28 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Wang, C., Geng, Y., Sun, Q., Xu, J. & Lu, Y. A sustainable and efficient artificial microgel system: toward creating a configurable synthetic cell. Small 16, 2002313 (2020).

    Article  CAS  Google Scholar 

  240. Nöth, M. et al. Biocatalytic microgels (μ-Gelzymes): synthesis, concepts, and emerging applications. Green Chem. 22, 8183–8209 (2020).

    Article  Google Scholar 

  241. Lai, E., Wang, Y., Wei, Y., Li, G. & Ma, G. Covalent immobilization of trypsin onto thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid) microspheres with high activity and stability. J. Appl. Polym. Sci. 133, 43343 (2016).

    Article  CAS  Google Scholar 

  242. Welsch, N., Wittemann, A. & Ballauff, M. Enhanced activity of enzymes immobilized in thermoresponsive core-shell microgels. J. Phys. Chem. B 113, 16039–16045 (2009).

    Article  CAS  PubMed  Google Scholar 

  243. Wan, L. et al. Programmable self-assembly of DNA-protein hybrid hydrogel for enzyme encapsulation with enhanced biological stability. Biomacromolecules 17, 1543–1550 (2016).

    Article  CAS  PubMed  Google Scholar 

  244. Köhler, T. et al. Cell-free protein synthesis and: in situ immobilization of deGFP-MatB in polymer microgels for malonate-to-malonyl CoA conversion. RSC Adv. 10, 40588–40596 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  245. Kleinschmidt, D. et al. Enhanced catalyst performance through compartmentalization exemplified by colloidal l-proline modified microgel catalysts. J. Colloid Interface Sci. 559, 76–87 (2020).

    Article  CAS  PubMed  Google Scholar 

  246. Mariconti, M., Morel, M., Baigl, D. & Rudiuk, S. Enzymatically active DNA-protein nanogels with tunable cross-linking density. Biomacromolecules 22, 3431–3439 (2021).

    Article  CAS  PubMed  Google Scholar 

  247. Singh, N., Lainer, B., Formon, G. J. M., De Piccoli, S. & Hermans, T. M. Re-programming hydrogel properties using a fuel-driven reaction cycle. J. Am. Chem. Soc. 142, 4083–4087 (2020).

    Article  CAS  PubMed  Google Scholar 

  248. Che, H., Buddingh’, B. C. & van Hest, J. C. M. Self-regulated and temporal control of a “breathing” microgel mediated by enzymatic reaction. Angew. Chem. Int. Ed. 56, 12581–12585 (2017).

    Article  CAS  Google Scholar 

  249. Merindol, R., Martin, N., Beneyton, T., Baret, J. C. & Ravaine, S. Fast and ample light controlled actuation of monodisperse all-DNA microgels. Adv. Funct. Mater. 31, 2010396 (2021).

    Article  CAS  Google Scholar 

  250. Song, J. et al. A RNA producing DNA hydrogel as a platform for a high performance RNA interference system. Nat. Commun. 9, 4331 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  251. Song, J. et al. Living-DNA nanogel appendant enables in situ modulation and quantification of regulation effects on membrane proteins. ACS Appl. Bio Mater. 4, 4565–4574 (2021).

    Article  CAS  PubMed  Google Scholar 

  252. Simpson, L. W., Good, T. A. & Leach, J. B. Protein folding and assembly in confined environments: implications for protein aggregation in hydrogels and tissues. Biotechnol. Adv. 42, 107573 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Altamura, E. et al. Chromatophores efficiently promote light-driven ATP synthesis and DNA transcription inside hybrid multicompartment artificial cells. Proc. Natl Acad. Sci. USA 118, e2012170118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Pérez-Luna, V. H. & González-Reynoso, O. Encapsulation of biological agents in hydrogels for therapeutic applications. Gels 4, 61 (2018).

    Article  PubMed Central  CAS  Google Scholar 

  255. Kanai, T., Nakai, H., Yamada, A., Fukuyama, M. & Weitz, D. A. Preparation of monodisperse hybrid gel particles with various morphologies via flow rate and temperature control. Soft Matter 15, 6934–6937 (2019).

    Article  CAS  PubMed  Google Scholar 

  256. Walker, S. A., Kennedy, M. T. & Zasadzinski, J. A. Encapsulation of bilayer vesicles by self-assembly. Nature 387, 61–64 (1997).

    Article  CAS  PubMed  Google Scholar 

  257. Shetty, S. C. et al. Directed signaling cascades in monodisperse artificial eukaryotic cells. ACS Nano 15, 15656–15666 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  258. Buck, S. et al. Engineering lipobeads: properties of the hydrogel core and the lipid bilayer shell. Biomacromolecules 5, 2230–2237 (2004).

    Article  CAS  PubMed  Google Scholar 

  259. Lester, C. L., Smith, S. M., Colson, C. D. & Guymon, C. A. Physical properties of hydrogels synthesized from lyotropic liquid crystalline templates. Chem. Mater. 15, 3376–3384 (2003).

    Article  CAS  Google Scholar 

  260. Saleem, Q., Liu, B., Gradinaru, C. C. & MacDonald, P. M. Lipogels: single-lipid-bilayer-enclosed hydrogel spheres. Biomacromolecules 12, 2364–2374 (2011).

    Article  CAS  PubMed  Google Scholar 

  261. Campbell, A., Taylor, P., Cayre, O. J. & Paunov, V. N. Preparation of aqueous gel beads coated by lipid bilayers. Chem. Comm. 21, 2378–2379 (2004).

    Article  CAS  Google Scholar 

  262. Abele, T. et al. Two-photon 3D laser printing inside synthetic cells. Adv. Mater. 34, e2106709 (2022).

    Article  PubMed  CAS  Google Scholar 

  263. Walther, T., Jahnke, K., Abele, T. & Göpfrich, K. Printing and erasing of DNA-based photoresists inside synthetic cells. Adv. Funct. Mater. 32, 2200762 (2022).

    Article  CAS  Google Scholar 

  264. Torres-Martínez, A., Angulo-Pachón, C. A., Galindo, F. & Miravet, J. F. Liposome-enveloped molecular nanogels. Langmuir 35, 13375–13381 (2019).

    Article  PubMed  CAS  Google Scholar 

  265. Martí-Centelles, R., Rubio-Magnieto, J. & Escuder, B. A minimalistic catalytically-active cell mimetic made of a supra-molecular hydrogel encapsulated into a polymersome. Chem. Commun. 56, 14487–14490 (2020).

    Article  Google Scholar 

  266. Jesorka, A., Markström, M., Karlsson, M. & Orwar, O. Controlled hydrogel formation in the internal compartment of giant unilamellar vesicles. J. Phys. Chem. B 109, 14759–14763 (2005).

    Article  CAS  PubMed  Google Scholar 

  267. Huang, A. et al. BiobitsTM explorer: a modular synthetic biology education kit. Sci. Adv. 4, eaat5105 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  268. De Geest, B. G. et al. Self-exploding lipid-coated microgels. Biomacromolecules 7, 373–379 (2006).

    Article  PubMed  CAS  Google Scholar 

  269. Kazakov, S., Kaholek, M., Teraoka, I. & Levon, K. UV-induced gelation on nanometer scale using liposome reactor. Macromolecules 35, 1911–1920 (2002).

    Article  CAS  Google Scholar 

  270. Fern, J. & Schulman, R. Modular DNA strand-displacement controllers for directing material expansion. Nat. Commun. 9, 3766 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  271. Wang, M. et al. Assembling responsive microgels at responsive lipid membranes. Proc. Natl Acad. Sci. USA 116, 5442–5450 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  272. Kazakov, S. et al. Poly(N-isopropylacrylamide-co-1-vinylimidazole) hydrogel nanoparticles prepared and hydrophobically modified in liposome reactors: atomic force microscopy and dynamic light scattering study. Langmuir 19, 8086–8093 (2003).

    Article  CAS  Google Scholar 

  273. Park, P. S. H. et al. Characterization of radioligand binding to a transmembrane receptor reconstituted into lipobeads. FEBS Lett. 567, 344–348 (2004).

    Article  CAS  PubMed  Google Scholar 

  274. Frank, P. et al. Proteo-lipobeads for the oriented encapsulation of membrane proteins. Soft Matter 11, 2906–2908 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  275. Makhoul-Mansour, M. M. et al. A skin-inspired soft material with directional mechanosensation. Bioinspir. Biomim. 16, abf746 (2021).

    Article  CAS  Google Scholar 

  276. Jia, H. et al. Shaping giant membrane vesicles in 3D-printed protein hydrogel cages. Small 16, 1906259 (2020).

    Article  CAS  Google Scholar 

  277. Bansil, R., Stanley, E. & Thomas LaMont, J. Mucin biophysics. Annu. Rev. Physiol. 57, 635–657 (1995).

    Article  CAS  PubMed  Google Scholar 

  278. Costerton, J. W., Lewandowski, Z., Caldwell, D. E., Korber, D. R. & Lappin-Scott, H. M. Microbial biofilms. Annu. Rev. Microbiol. 49, 711–745 (1995).

    Article  CAS  PubMed  Google Scholar 

  279. Ahmadi, F., Oveisi, Z., Samani, M. & Amoozgar, Z. Chitosan based hydrogels: characteristics and pharmaceutical applications. Res. Pharm. Sci. 10, 1–16 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  280. Sapra, K. T. & Bayley, H. Lipid-coated hydrogel shapes as components of electrical circuits and mechanical devices. Sci. Rep. 2, 848 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  281. Falk, B., Garramone, S. & Shivkumar, S. Diffusion coefficient of paracetamol in a chitosan hydrogel. Mater. Lett. 58, 3261–3265 (2004).

    Article  CAS  Google Scholar 

  282. Amsden, B. Solute diffusion within hydrogels. Mechanisms models. Macromolecules 31, 8382–8395 (1998).

    Article  CAS  Google Scholar 

  283. Sandrin, D. et al. Diffusion of macromolecules in a polymer hydrogel: from microscopic to macroscopic scales. Phys. Chem. Chem. Phys. 18, 12860–12876 (2016).

    Article  CAS  PubMed  Google Scholar 

  284. Czerner, M., Fellay, L. S., Suárez, M. P., Frontini, P. M. & Fasce, L. A. Determination of elastic modulus of gelatin gels by indentation experiments. Procedia Mater. Sci. 8, 287–296 (2015).

    Article  CAS  Google Scholar 

  285. Bromberg, L. Scaling of rheological properties of hydrogels from associating polymers. Macromolecules 31, 6148–6156 (1998).

    Article  CAS  Google Scholar 

  286. Atik, A. F. et al. Hyaluronic acid based low viscosity hydrogel as a novel carrier for convection enhanced delivery of CAR T cells. J. Clin. Neurosci. 56, 163–168 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  287. Korson, L., Drost-Hansen, W. & Millero, F. J. Viscosity of water at various temperatures. J. Phys. Chem. 73, 34–39 (1969).

    Article  CAS  Google Scholar 

  288. Fushimi, K. & Verkman, A. S. Low viscosity in the aqueous domain of cell cytoplasm measured by picosecond polarization microfluorimetry. J. Cell Biol. 112, 719–725 (1991).

    Article  CAS  PubMed  Google Scholar 

  289. Liu, H. et al. In situ mechanical characterization of the cell nucleus by atomic force microscopy. ACS Nano 8, 3821–3828 (2014).

    Article  CAS  PubMed  Google Scholar 

  290. Novak, I. L., Kraikivski, P. & Slepchenko, B. M. Diffusion in cytoplasm: effects of excluded volume due to internal membranes and cytoskeletal structures. Biophys. J. 97, 758–767 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  291. Gardel, M. L., Kasza, K. E., Brangwynne, C. P., Liu, J. & Weitz, D. A. Chapter 19: mechanical response of cytoskeletal networks. Methods Cell Biol. 89, 487–519 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  292. Kihara, T., Ito, J. & Miyake, J. Measurement of biomolecular diffusion in extracellular matrix condensed by fibroblasts using fluorescence correlation spectroscopy. PLoS ONE 8, 82382 (2013).

    Article  CAS  Google Scholar 

  293. Nebuloni, M. et al. Insight on colorectal carcinoma infiltration by studying perilesional extracellular matrix. Sci. Rep. 6, 22522 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  294. Fernández-Pérez, J. & Ahearne, M. The impact of decellularization methods on extracellular matrix derived hydrogels. Sci. Rep. 9, 14933 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  295. Jalalvandi, E., Hanton, L. R. & Moratti, S. C. Schiff-base based hydrogels as degradable platforms for hydrophobic drug delivery. Eur. Polym. J. 90, 13–24 (2017).

    Article  CAS  Google Scholar 

  296. Okudan, A. & Altay, A. Investigation of the effects of different hydrophilic and hydrophobic comonomers on the volume phase transition temperatures and thermal properties of N-isopropylacrylamide-based hydrogels. Int. J. Polym. Sci. 2019, 7324181 (2019).

    Article  CAS  Google Scholar 

  297. Wang, Y. et al. Chitosan cross-linked poly(acrylic acid) hydrogels: drug release control and mechanism. Colloids Surf. B Biointerfaces 152, 252–259 (2017).

    Article  CAS  PubMed  Google Scholar 

  298. Katono, H., Sanui, K., Ogata, N., Okano, T. & Sakurai, Y. On-off drug release mechanism from thermo-responsive IPNs composed of poly(acrylamide-co-butyl methacrylate) and poly(acrylic acid). Jpn J. Artif. Organs 21, 239–243 (1992).

    Google Scholar 

  299. Burmistrova, A., Richter, M., Uzum, C. & Klitzing, R. V. Effect of cross-linker density of P(NIPAM-co-AAc) microgels at solid surfaces on the swelling/shrinking behaviour and the Young’s modulus. Colloid Polym. Sci. 289, 613–624 (2011).

    Article  CAS  Google Scholar 

  300. Kong, H. J., Alsberg, E., Kaigler, D., Lee, K. Y. & Mooney, D. J. Controlling degradation of hydrogels via the size of cross-linked junctions. Adv. Mater. 16, 1917–1921 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  301. Ashraf, S., Park, H. K., Park, H. & Lee, S. H. Snapshot of phase transition in thermoresponsive hydrogel PNIPAM: role in drug delivery and tissue engineering. Macromol. Res. 24, 297–304 (2016).

    Article  CAS  Google Scholar 

  302. Kim, A., Mujumdar, S. K. & Siegel, R. A. Swelling properties of hydrogels containing phenylboronic acids. Chemosensors 2, 1–12 (2014).

    Article  Google Scholar 

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Acknowledgements

This work was supported by a UK Research and Innovation (UKRI) Future Leaders Fellowship, grant reference number MR/S031537/1 (awarded to Y.E.); an Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training Studentship from the Institute of Chemical Biology, grant reference number EP/S023518 (awarded to M.E.A.), an EPSRC Doctoral Prize Fellowship (awarded to J.W.H.) and an EPSRC grant, reference number EP/V048651/1.

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Authors and Affiliations

  1. Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, London, UK

    Matthew E. Allen, James W. Hindley & Oscar Ces

  2. Department of Chemical Engineering, Imperial College London, London, UK

    Matthew E. Allen, Divesh K. Baxani & Yuval Elani

  3. Institute of Chemical Biology, Imperial College London, Molecular Sciences Research Hub, London, UK

    Matthew E. Allen, James W. Hindley, Divesh K. Baxani, Oscar Ces & Yuval Elani

  4. fabriCELL, Imperial College London and King’s College London, London, UK

    Matthew E. Allen, James W. Hindley, Divesh K. Baxani, Oscar Ces & Yuval Elani

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M.E.A., J.W.H. and Y.E. proposed the framework of this Review. All authors contributed through researching, writing and editing the Review.

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Glossary

Artificial cell

An engineered device that attempts to mimic the form, function and/or behaviours of biological cells.

Synthetic biology

A field that involves the redesign of existing organisms (top down) or the construction of new cell-like entities from molecular building blocks (bottom up).

Vesicle

Aqueous compartment coated with a bilayer of amphiphilic molecules (usually lipids).

Coacervates

A colloid rich aqueous phase that is formed through liquid–liquid phase separation.

Nanogel

A nanoparticle (nanometre size) that comprises a hydrogel network.

Microgel

A microparticle (micrometre size) that comprises a hydrogel network.

Droplet interface bilayer

(DIB). A lipid bilayer that is formed between aqueous droplets in oil from the contact of water–oil interfaces in the presence of a suitable phospholipid.

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Allen, M.E., Hindley, J.W., Baxani, D.K. et al. Hydrogels as functional components in artificial cell systems. Nat Rev Chem 6, 562–578 (2022). https://doi.org/10.1038/s41570-022-00404-7

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