Bioactuators based on stimulus-responsive hydrogels and their emerging biomedical applications
Source abstract
Abstract
Abstract The increasingly intimate bond connecting soft actuation devices and emerging biomedical applications is triggering the development of novel materials with superb biocompatibility and a sensitive actuation capability that can reliably function as bio-use-oriented actuators in a human-friendly manner. Stimulus-responsive hydrogels are biocompatible with human tissues/organs, have sufficient water content, are similar to extracellular matrices in structure and chemophysical properties, and are responsive to external environmental stimuli, and these materials have recently attracted massive research interest for fabricating bioactuators. The great potential of employing such hydrogels that respond to various stimuli (e.g., pH, temperature, light, electricity, and magnetic fields) for actuation purposes has been revealed by their performances in real-time biosensing systems, targeted drug delivery, artificial muscle reconstruction, and cell microenvironment engineering. In this review, the material selection of hydrogels with multiple stimulus-responsive mechanisms for actuator fabrication is first introduced, followed by a detailed introduction to and discussion of the most recent progress in emerging biomedical applications of hydrogel-based bioactuators. Final conclusions, existing challenges, and upcoming development prospects are noted in light of the status quo of bioactuators based on stimulus-responsive hydrogels.
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Research context
OpenAlex topics: Advanced Sensor and Energy Harvesting Materials · Advanced Materials and Mechanics · Hydrogels: synthesis, properties, applications
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References (100+)
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1. Morin, S. A. et al. Camouflage and display for soft machines. Science 337, 828–832 (2012).10.1126/science.1222149 ↗
2. Rus, D. & Tolley, M. T. Design, fabrication and control of soft robots. Nature 521, 467–475 (2015).10.1038/nature14543 ↗
3. Bartlett, N. W. et al. A 3D-printed, functionally graded soft robot powered by combustion. Science 349, 161–165 (2015).10.1126/science.aab0129 ↗
4. Nawroth, J. C. et al. A tissue-engineered jellyfish with biomimetic propulsion. Nat. Biotechnol. 30, 792–797 (2012).10.1038/nbt.2269 ↗
5. Shepherd, R. F. et al. Multigait soft robot. Proc. Natl Acad. Sci. USA 108, 20400–20403 (2011).10.1073/pnas.1116564108 ↗
6. Tolley, M. T. et al. A resilient, untethered soft robot. Soft Robot. 1, 213–223 (2014).10.1089/soro.2014.0008 ↗
7. Brown, E. et al. Universal robotic gripper based on the jamming of granular material. Proc. Natl Acad. Sci. USA 107, 18809–18814 (2010).10.1073/pnas.1003250107 ↗
8. Martinez, R. V. et al. Robotic tentacles with three-dimensional mobility based on flexible elastomers. Adv. Mater. 25, 205–212 (2013).10.1002/adma.201203002 ↗
9. Ilievski, F., Mazzeo, A. D., Shepherd, R. F., Chen, X. & Whitesides, G. M. Soft robotics for chemists. Angew. Chem. 50, 1890–1895 (2011).10.1002/anie.201006464 ↗
10. Beregoi, M., Evanghelidis, A., Diculescu, V. C., Iovu, H. & Enculescu, I. Polypyrrole actuator based on electrospun microribbons. ACS Appl. Mater. Interfaces 9, 38068–38075 (2017).10.1021/acsami.7b13196 ↗
11. Zhang, L. & Naumov, P. Frontispiece: light‐ and humidity‐induced motion of an acidochromic film. Angew. Chem. 54, 8642 (2015).10.1002/anie.201504153 ↗
12. García-Córdova, F., Valero, L., Ismail, Y. A. & Otero, T. F. Biomimetic polypyrrole based all three-in-one triple layer sensing actuators exchanging cations. J. Mater. Chem. 21, 17265 (2011).10.1039/c1jm13374h ↗
13. Acome, E. et al. Hydraulically amplified self-healing electrostatic actuators with muscle-like performance. Science 359, 61–65 (2018).10.1126/science.aao6139 ↗
14. Wang, C. et al. Soft ultrathin electronics innervated adaptive fully soft robots. Adv. Mater. 30, 1706695 (2018).10.1002/adma.201706695 ↗
15. Roy, S., Kim, J., Kotal, M., Kim, K. J. & Oh, I.-K. Electroionic antagonistic muscles based on nitrogen-doped carbons derived from poly(triazine-triptycene). Adv. Sci. 4, 1700410 (2017).10.1002/advs.201700410 ↗
16. Roche, E. T. et al. A bioinspired soft actuated material. Adv. Mater. 26, 1200–1206 (2014).10.1002/adma.201304018 ↗
17. Shao, J. et al. Chemotaxis‐guided hybrid neutrophil micromotor for actively targeted drug transport. Angew. Chem. Int. Ed. 56, 12935–12939 (2017).10.1002/anie.201706570 ↗
18. de Avila, B. E. et al. Micromotor-enabled active drug delivery for in vivo treatment of stomach infection. Nat. Commun. 8, 272 (2017).
19. Li, J. et al. Enteric micromotor can selectively position and spontaneously propel in the gastrointestinal tract. ACS Nano 10, 9536–9542 (2016).10.1021/acsnano.6b04795 ↗
20. Lowenberg, C., Balk, M., Wischke, C., Behl, M. & Lendlein, A. Shape-memory hydrogels: evolution of structural principles to enable shape switching of hydrophilic polymer networks. Acc. Chem. Res. 50, 723–732 (2017).10.1021/acs.accounts.6b00584 ↗
21. Huang, G. et al. Functional and biomimetic materials for engineering of the three-dimensional cell microenvironment. Chem. Rev. 117, 12764–12850 (2017).10.1021/acs.chemrev.7b00094 ↗
22. Wei, M., Gao, Y., Li, X. & Serpe, M. J. Stimuli-responsive polymers and their applications. Polym. Chem. 8, 127–143 (2017).10.1039/C6PY01585A ↗
23. Chen, X. & Dai, H.-H. Swelling and instability of a gel annulus. Acta Mech. Sin. 31, 627–636 (2015).10.1007/s10409-015-0496-4 ↗
24. Kim, M., Jung, B. & Park, J.-H. Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin. Biomaterials 33, 668–678 (2012).10.1016/j.biomaterials.2011.09.074 ↗
25. Liu, S. et al. Reaction-induced swelling of ionic gels. Soft Matter 11, 449–455 (2015).10.1039/C4SM02252A ↗
26. Sidorenko, A., Krupenkin, T., Taylor, A., Fratzl, P. & Aizenberg, J. Reversible switching of hydrogel-actuated nanostructures into complex micropatterns. Science 315, 487–490 (2007).10.1126/science.1135516 ↗
27. Nakahata, M., Takashima, Y., Hashidzume, A. & Harada, A. Redox-generated mechanical motion of a supramolecular polymeric actuator based on host–guest interactions. Angew. Chem. 52, 5731–5735 (2013).10.1002/anie.201300862 ↗
28. Palleau, E., Morales, D., Dickey, M. D. & Velev, O. D. Reversible patterning and actuation of hydrogels by electrically assisted ionoprinting. Nat. Commun. 4, 2257 (2013).10.1038/ncomms3257 ↗
29. Caliari, S. R. & Burdick, J. A. A practical guide to hydrogels for cell culture. Nat. Methods 13, 405 (2016).10.1038/nmeth.3839 ↗
30. DeForest, C. A. & Anseth, K. S. Advances in bioactive hydrogels to probe and direct cell fate. Annu. Rev. Chem. Biomol. Eng. 3, 421–444 (2012).10.1146/annurev-chembioeng-062011-080945 ↗
31. 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).10.1016/j.mser.2015.04.001 ↗
32. Li, Y. et al. Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions. NPG Asia Mater. 8, e238–e238 (2016).10.1038/am.2015.148 ↗
33. Li, Y. et al. Chinese-noodle-inspired muscle myofiber fabrication. Adv. Funct. Mater. 25, 5999–6008 (2015).10.1002/adfm.201502018 ↗
34. Li, Y. et al. An approach to quantifying 3D responses of cells to extreme strain. Sci. Rep. 6, 19550 (2016).
35. Gupta, P., Vermani, K. & Garg, S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug Discov. Today 7, 569–579 (2002).10.1016/S1359-6446(02)02255-9 ↗
36. Kocak, G., Tuncer, C. & Bütün, V. pH-Responsive polymers. Polym. Chem. 8, 144–176 (2017).10.1039/C6PY01872F ↗
37. Beebe, D. J. et al. Functional hydrogel structures for autonomous flow control inside microfluidic channels. Nature 404, 588–590 (2000).10.1038/35007047 ↗
38. Liu, R. H., Qing, Y. & Beebe, D. J. Fabrication and characterization of hydrogel-based microvalves. J. Microelectromech. Syst. 11, 45–53 (2002).10.1109/84.982862 ↗
39. Shim, T. S., Kim, S. H., Heo, C. J., Jeon, H. C. & Yang, S. M. Controlled origami folding of hydrogel bilayers with sustained reversibility for robust microcarriers. Angew. Chem. 51, 1420–1423 (2012).10.1002/anie.201106723 ↗
40. Nakagawa, H., Hara, Y., Maeda, S. & Hasimoto, S. A pendulum-like motion of nanofiber gel actuator synchronized with external periodic pH oscillation. Polymers 3, 405–412 (2011).10.3390/polym3010405 ↗
41. Bassil, M., Davenas, J. & El Tahchi, M. Electrochemical properties and actuation mechanisms of polyacrylamide hydrogel for artificial muscle application. Sens. Actuators B: Chem. 134, 496–501 (2008).10.1016/j.snb.2008.05.025 ↗
42. Techawanitchai, P. et al. Photo-switchable control of pH-responsive actuators via pH jump reaction. Soft Matter 8, 2844–2851 (2012).10.1039/c2sm07277g ↗
43. Guo, W. et al. pH-stimulated DNA hydrogels exhibiting shape-memory properties. Adv. Mater. 27, 73–78 (2015).10.1002/adma.201403702 ↗
44. Lee, B. P. & Konst, S. Novel hydrogel actuator inspired by reversible mussel adhesive protein chemistry. Adv. Mater. 26, 3415–3419 (2014).10.1002/adma.201306137 ↗
45. Zhang, J. & Peppas, N. A. Synthesis and characterization of pH- and temperature-sensitive poly(methacrylic acid)/poly(N-isopropylacrylamide) interpenetrating polymeric networks. Macromolecules 33, 102–107 (2000).10.1021/ma991398q ↗
46. Bumsang, K., Kristen, L. F. & PN, A. Dynamic swelling behavior of pH‐sensitive anionic hydrogels used for protein delivery. J. Appl. Polym. Sci. 89, 1606–1613 (2003).10.1002/app.12337 ↗
47. Albright, V. et al. Self-defensive antibiotic-loaded layer-by-layer coatings: Imaging of localized bacterial acidification and pH-triggering of antibiotic release. Acta Biomater. 61, 66–74 (2017).10.1016/j.actbio.2017.08.012 ↗
48. Shin, M. K., Spinks, G. M., Shin, S. R., Kim, S. I. & Kim, S. J. Nanocomposite hydrogel with high toughness for bioactuators. Adv. Mater. 21, 1712–1715 (2009).10.1002/adma.200802205 ↗
49. Zhao, L. et al. pH and glucose dual-responsive injectable hydrogels with insulin and fibroblasts as bioactive dressings for diabetic wound healing. ACS Appl. Mater. Interfaces 9, 37563–37574 (2017).10.1021/acsami.7b09395 ↗
50. Jang, J.-H. & Park, S.-Y. pH-responsive cholesteric liquid crystal double emulsion droplets prepared by microfluidics. Sens. Actuators B: Chem. 241, 636–643 (2017).10.1016/j.snb.2016.10.118 ↗
51. Heskins, M. & Guillet, J. E. Solution properties of poly(N-isopropylacrylamide). J. Macromol. Sci.: Part A—Chem. 2, 1441–1455 (1968).10.1080/10601326808051910 ↗
52. Stoychev, G., Puretskiy, N. & Ionov, L. Self-folding all-polymer thermoresponsive microcapsules. Soft Matter 7, 3277–3279 (2011).10.1039/c1sm05109a ↗
53. Yoshida, R. et al. Comb-type grafted hydrogels with rapid deswelling response to temperature changes. Nature 374, 240 (1995).10.1038/374240a0 ↗
54. Kim, Y. S. et al. Thermoresponsive actuation enabled by permittivity switching in an electrostatically anisotropic hydrogel. Nat. Mater. 14, 1002 (2015).10.1038/nmat4363 ↗
55. Chen, J. P. & Cheng, T. H. Thermo-responsive chitosan-graft-poly(N-isopropylacrylamide) injectable hydrogel for cultivation of chondrocytes and meniscus cells. Macromol. Biosci. 6, 1026–1039 (2006).10.1002/mabi.200600142 ↗
56. Yavuz, M. S. et al. Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nat. Mater. 8, 935 (2009).10.1038/nmat2564 ↗
57. Jonas, A. M., Hu, Z., Glinel, K. & Huck, W. T. S. Effect of nanoconfinement on the collapse transition of responsive polymer brushes. Nano Lett. 8, 3819–3824 (2008).10.1021/nl802152q ↗
58. Hashimoto, K., Sakamoto, J. & Tanii, H. Neurotoxicity of acrylamide and related compounds and their effects on male gonads in mice. Arch. Toxicol. 47, 179–189 (1981).10.1007/BF00368678 ↗
59. Tanii, H. & Hashimoto, K. Neurotoxicity of acrylamide and related compounds in rats. Arch. Toxicol. 54, 203–213 (1983).10.1007/BF01239204 ↗
60. Loh, X. J. et al. Biodegradable thermogelling poly(ester urethane)s consisting of poly(lactic acid)— thermodynamics of micellization and hydrolytic degradation. Biomaterials 29, 2164–2172 (2008).10.1016/j.biomaterials.2008.01.016 ↗
61. Loh, X. J., Colin Sng, K. B. & Li, J. Synthesis and water-swelling of thermo-responsive poly(ester urethane)s containing poly(epsilon-caprolactone), poly(ethylene glycol) and poly(propylene glycol). Biomaterials 29, 3185–3194 (2008).10.1016/j.biomaterials.2008.04.015 ↗
62. Wu, W., Shen, J., Banerjee, P. & Zhou, S. Core–shell hybrid nanogels for integration of optical temperature-sensing, targeted tumor cell imaging, and combined chemo-photothermal treatment. Biomaterials 31, 7555–7566 (2010).10.1016/j.biomaterials.2010.06.030 ↗
63. Hao, L. et al. Thermo-responsive gels based on supramolecular assembly of an amidoamine and citric acid. Soft Matter 14, 432–439 (2018).10.1039/C7SM01592E ↗
64. Shiga, T. & Kurauchi, T. Deformation of polyelectrolyte gels under the influence of electric field. J. Appl. Polym. Sci. 39, 2305–2320 (1990).10.1002/app.1990.070391110 ↗
65. Gong, J. P., Nitta, T. & Osada, Y. Electrokinetic modeling of the contractile phenomena of polyelectrolyte gels. One-dimensional capillary model. J. Phys. Chem. 98, 9583–9587 (1994).10.1021/j100089a036 ↗
66. Guiseppi-Elie, A. Electroconductive hydrogels: synthesis, characterization and biomedical applications. Biomaterials 31, 2701–2716 (2010).10.1016/j.biomaterials.2009.12.052 ↗
67. Jeong, S., Jun Park, S., Shin, M.-S. & Kim, S. I. Characteristics of electrical responsive chitosan/polyallylamine interpenetrating polymer network hydrogel. J. Appl. Polym. Sci. 86, 2290–2295 (2002).10.1002/app.11217 ↗
68. Cheng, Y. et al. In situ quantitative visualization and characterization of chitosan electrodeposition with paired sidewall electrodes. Soft Matter 6, 3177–3183 (2010).10.1039/c0sm00124d ↗
69. Zolfagharian, A., Kouzani, A. Z., Khoo, S. Y., Nasri-Nasrabadi, B. & Kaynak, A. Development and analysis of a 3D printed hydrogel soft actuator. Sens. Actuators A: Phys. 265, 94–101 (2017).10.1016/j.sna.2017.08.038 ↗
70. Kim, S. J. et al. Behavior in electric fields of smart hydrogels with potential application as bio-inspired actuators. Smart Mater. Struct. 14, 511–514 (2005).10.1088/0964-1726/14/4/008 ↗
71. Han, D. et al. Soft robotic manipulation and locomotion with a 3D printed electroactive hydrogel. ACS Appl. Mater. Interfaces 10, 17512–17518 (2018).10.1021/acsami.8b04250 ↗
72. Tai, Z., Yang, J., Qi, Y., Yan, X. & Xue, Q. Synthesis of a graphene oxide–polyacrylic acid nanocomposite hydrogel and its swelling and electroresponsive properties. RSC Adv. 3, 12751–12757 (2013).10.1039/c3ra22335c ↗
73. Kwon, G. H., Jeong, G. S., Park, J. Y., Moon, J. H. & Lee, S. H. A low-energy-consumption electroactive valveless hydrogel micropump for long-term biomedical applications. Lab Chip 11, 2910–2915 (2011).10.1039/c1lc20288j ↗
74. Kwon, G. H. et al. Electrically-driven hydrogel actuators in microfluidic channels: fabrication, characterization, and biological application. Lab Chip 10, 1604–1610 (2010).10.1039/b926443d ↗
75. Kwon, G. H. et al. Biomimetic soft multifunctional miniature aquabots. Small 4, 2148–2153 (2008).10.1002/smll.200800315 ↗
76. Moschou, E. A., Peteu, S. F., Bachas, L. G., Madou, M. J. & Daunert, S. Artificial muscle material with fast electroactuation under neutral pH conditions. Chem. Mater. 16, 2499–2502 (2004).10.1021/cm049921p ↗
77. Osada, Y. & Gong, J. P. Soft and wet materials: polymer gels. Adv. Mater. 10, 827–837 (1999).10.1002/(SICI)1521-4095(199808)10:11<827::AID-ADMA827>3.0.CO;2-L ↗
78. Han, Y. L. et al. Directed self-assembly of microscale hydrogels by electrostatic interaction. Biofabrication 5, 035004 (2013).10.1088/1758-5082/5/3/035004 ↗
79. Yang, C. et al. Reduced graphene oxide-containing smart hydrogels with excellent electro-response and mechanical properties for soft actuators. ACS Appl. Mater. Interfaces 9, 15758–15767 (2017).10.1021/acsami.7b01710 ↗
80. Migliorini, L., Santaniello, T., Yan, Y., Lenardi, C. & Milani, P. Low-voltage electrically driven homeostatic hydrogel-based actuators for underwater soft robotics. Sens. Actuators B: Chem. 228, 758–766 (2016).10.1016/j.snb.2016.01.110 ↗
81. Zhang, N. et al. Actuator materials based on graphene oxide/polyacrylamide composite hydrogels prepared by in situ polymerization. Soft Matter 7, 7231–7239 (2011).10.1039/c1sm05498h ↗
82. Goponenko, A. V. & Dzenis, Y. A. Role of mechanical factors in applications of stimuli-responsive polymer gels—status and prospects. Polymer 101, 415–449 (2016).10.1016/j.polymer.2016.08.068 ↗
83. Li, Y. et al. Magnetic hydrogels and their potential biomedical applications. Adv. Funct. Mater. 23, 660–672 (2013).10.1002/adfm.201201708 ↗
84. Liu, H. et al. Magnetic steering of liquid metal mobiles. Soft Matter 14, 3236–3245 (2018).10.1039/C8SM00056E ↗
85. Kim, Y., Yuk, H., Zhao, R., Chester, S. A. & Zhao, X. Printing ferromagnetic domains for untethered fast-transforming soft materials. Nature 558, 274–279 (2018).10.1038/s41586-018-0185-0 ↗
86. Okochi, M. et al. Three-dimensional cell culture array using magnetic force-based cell patterning for analysis of invasive capacity of BALB/3T3/v-src. Lab Chip 9, 3378–3384 (2009).10.1039/b909304d ↗
87. Kim, J. A. et al. High-throughput generation of spheroids using magnetic nanoparticles for three-dimensional cell culture. Biomaterials 34, 8555–8563 (2013).10.1016/j.biomaterials.2013.07.056 ↗
88. Xu, F. et al. Three-dimensional magnetic assembly of microscale hydrogels. Adv. Mater. 23, 4254–4260 (2011).10.1002/adma.201101962 ↗
89. Ramanujan, R. V. & Lao, L. L. The mechanical behavior of smart magnet–hydrogel composites. Smart Mater. Struct. 15, 952–956 (2006).10.1088/0964-1726/15/4/008 ↗
90. Ozay, O., Ekici, S., Baran, Y., Aktas, N. & Sahiner, N. Removal of toxic metal ions with magnetic hydrogels. Water Res. 43, 4403–4411 (2009).10.1016/j.watres.2009.06.058 ↗
91. Souza, G. R. et al. Three-dimensional tissue culture based on magnetic cell levitation. Nat. Nanotechnol. 5, 291 (2010).10.1038/nnano.2010.23 ↗
92. Zhou, Y. et al. Hierarchically structured free-standing hydrogels with liquid crystalline domains and magnetic nanoparticles as dual physical cross-linkers. J. Am. Chem. Soc. 134, 1630–1641 (2012).10.1021/ja208349x ↗
93. Li, Y. et al. Non-contact tensile viscoelastic characterization of microscale biological materials. Acta Mech. Sin. 34, 589–599 (2018).10.1007/s10409-017-0740-1 ↗
94. Wei, L., Yang, G., Wang, R. & Ma, W. Selective adsorption and separation of chromium (VI) on the magnetic iron–nickel oxide from waste nickel liquid. J. Hazard. Mater. 164, 1159–1163 (2009).10.1016/j.jhazmat.2008.09.016 ↗
95. Mourran, A., Zhang, H., Vinokur, R. & Moller, M. Soft microrobots employing nonequilibrium actuation via plasmonic heating. Adv. Mater. 29, 1604825 (2017).10.1002/adma.201604825 ↗
96. Wang, E., Desai, M. S. & Lee, S. W. Light-controlled graphene-elastin composite hydrogel actuators. Nano Lett. 13, 2826–2830 (2013).10.1021/nl401088b ↗
97. Peng, K., Tomatsu, I. & Kros, A. Light controlled protein release from a supramolecular hydrogel. Chem. Commun. 46, 4094–4096 (2010).10.1039/c002565h ↗
98. Zhao, Y.-L. & Stoddart, J. F. Azobenzene-based light-responsive hydrogel system. Langmuir 25, 8442–8446 (2009).10.1021/la804316u ↗
99. Yin, S.-N., Wang, C.-F., Liu, S.-S. & Chen, S. Facile fabrication of tunable colloidal photonic crystal hydrogel supraballs toward a colorimetric humidity sensor. J. Mater. Chem. C 1, 4685–4690 (2013).10.1039/c3tc30659c ↗
100. Kim, E., Kim, S. Y., Jo, G., Kim, S. & Park, M. J. Colorimetric and resistive polymer electrolyte thin films for real-time humidity sensors. ACS Appl. Mater. Interfaces 4, 5179–5187 (2012).10.1021/am3011115 ↗