Skip to main content

Tunable Hydrogels: Introduction to the World of Smart Materials for Biomedical Applications

Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE,volume 178)

Abstract

Hydrogels are hydrated polymers that are able to mimic many of the properties of living tissues. For this reason, they have become a popular choice of biomaterial in many biomedical applications including tissue engineering, drug delivery, and biosensing. The physical and biological requirements placed on hydrogels in these contexts are numerous and require a tunable material, which can be adapted to meet these demands. Tunability is defined as the use of knowledge-based tools to manipulate material properties in the desired direction. Engineering of suitable mechanical properties and integrating bioactivity are two major aspects of modern hydrogel design. Beyond these basic features, hydrogels can be tuned to respond to specific environmental cues and external stimuli, which are provided by surrounding cells or by the end user (patient, clinician, or researcher). This turns tunable hydrogels into stimulus-responsive smart materials, which are able to display adaptable and dynamic properties. In this book chapter, we will first shortly cover the foundation of hydrogel tunability, related to mechanical properties and biological functionality. Then, we will move on to stimulus-responsive hydrogel systems and describe their basic design, as well as give examples of their application in diverse biomedical fields. As both the understanding of underlying biological mechanisms and our engineering capacity mature, even more sophisticated tunable hydrogels addressing specific therapeutic goals will be developed.

Graphical Abstract

Keywords

  • Biomedical applications
  • Biosensors
  • Drug delivery
  • Hydrogel
  • Smart
  • Soft actuators
  • Stimulus-responsive
  • Tissue engineering
  • Tunable

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   299.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   379.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Hoffman AS (2012) Hydrogels for biomedical applications. Adv Drug Deliv Rev 64:18–23

    CrossRef  Google Scholar 

  2. Seliktar D (2012) Designing cell-compatible hydrogels for biomedical applications. Science 336(6085):1124–1128

    CrossRef  CAS  PubMed  Google Scholar 

  3. Kamoun EA, Kenawy E-RS, Chen X (2017) A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings. J Adv Res 8(3):217–233

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  4. Malda J et al (2013) 25th anniversary article: engineering hydrogels for biofabrication. Adv Mater 25(36):5011–5028

    CrossRef  CAS  PubMed  Google Scholar 

  5. Champeau M et al (2020) 4D printing of hydrogels: a review. Adv Funct Mater 30(31):1910606

    CrossRef  CAS  Google Scholar 

  6. Khademhosseini A, Langer R (2007) Microengineered hydrogels for tissue engineering. Biomaterials 28(34):5087–5092

    CrossRef  CAS  PubMed  Google Scholar 

  7. Bosworth LA, Turner L-A, Cartmell SH (2013) State of the art composites comprising electrospun fibres coupled with hydrogels: a review. Nanomedicine 9(3):322–335

    CrossRef  CAS  PubMed  Google Scholar 

  8. Ruedinger F et al (2015) Hydrogels for 3D mammalian cell culture: a starting guide for laboratory practice. Appl Microbiol Biotechnol 99(2):623–636

    CrossRef  CAS  PubMed  Google Scholar 

  9. Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101(7):1869–1880

    CrossRef  CAS  PubMed  Google Scholar 

  10. Caliari SR, Burdick JA (2016) A practical guide to hydrogels for cell culture. Nat Methods 13(5):405–414

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  11. Thiele J et al (2014) 25th anniversary article: designer hydrogels for cell cultures: a materials selection guide. Adv Mater 26(1):125–148

    CrossRef  CAS  PubMed  Google Scholar 

  12. Jiang Y et al (2014) Click hydrogels, microgels and nanogels: Emerging platforms for drug delivery and tissue engineering. Biomaterials 35(18):4969–4985

    CrossRef  CAS  PubMed  Google Scholar 

  13. Hennink WE, van Nostrum CF (2012) Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev 64:223–236

    CrossRef  Google Scholar 

  14. Hu W et al (2019) Advances in crosslinking strategies of biomedical hydrogels. Biomater Sci 7(3):843–855

    CrossRef  CAS  PubMed  Google Scholar 

  15. DeForest CA, Anseth KS (2012) Advances in bioactive hydrogels to probe and direct cell fate. Ann Rev Chem Biomol Eng 3:421–444

    CrossRef  CAS  Google Scholar 

  16. Oyen M (2014) Mechanical characterisation of hydrogel materials. Int Mater Rev 59(1):44–59

    CrossRef  CAS  Google Scholar 

  17. Yue K et al (2015) Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials 73:254–271

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pepelanova I et al (2018) Gelatin-methacryloyl (GelMA) hydrogels with defined degree of functionalization as a versatile toolkit for 3D cell culture and extrusion bioprinting. Bioengineering 5(3):55

    CrossRef  CAS  PubMed Central  Google Scholar 

  19. Dragan ES (2014) Design and applications of interpenetrating polymer network hydrogels. A review. Chem Eng J 243:572–590

    CrossRef  CAS  Google Scholar 

  20. Silverstein MS (2020) Interpenetrating polymer networks: so happy together? Polymer 207:122929

    CrossRef  CAS  Google Scholar 

  21. Munoz-Pinto DJ et al (2015) Characterization of sequential collagen-poly (ethylene glycol) diacrylate interpenetrating networks and initial assessment of their potential for vascular tissue engineering. Biomaterials 40:32–42

    CrossRef  CAS  PubMed  Google Scholar 

  22. Chen Q et al (2015) Fundamentals of double network hydrogels. J Mater Chem B 3(18):3654–3676

    CrossRef  CAS  PubMed  Google Scholar 

  23. Yasuda K et al (2005) Biomechanical properties of high-toughness double network hydrogels. Biomaterials 26(21):4468–4475

    CrossRef  CAS  PubMed  Google Scholar 

  24. Azuma C et al (2007) Biodegradation of high-toughness double network hydrogels as potential materials for artificial cartilage. J Biomed Mater Res Part A 81(2):373–380

    CrossRef  CAS  Google Scholar 

  25. Buwalda SJ et al (2012) Stereocomplexed 8-armed poly (ethylene glycol)–poly (lactide) star block copolymer hydrogels: gelation mechanism, mechanical properties and degradation behavior. Polymer 53(14):2809–2817

    CrossRef  CAS  Google Scholar 

  26. Wang H et al (2014) Cell-laden photocrosslinked GelMA–DexMA copolymer hydrogels with tunable mechanical properties for tissue engineering. J Mater Sci Mater Med 25(9):2173–2183

    CrossRef  CAS  PubMed  Google Scholar 

  27. Lam T et al (2019) Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue-engineered cartilage. J Biomed Mater Res B Appl Biomater 107(8):2649–2657

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  28. Jeon O, Wolfson DW, Alsberg E (2015) In-situ formation of growth-factor-loaded coacervate microparticle-embedded hydrogels for directing encapsulated stem cell fate. Adv Mater 27(13):2216–2223

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gaharwar AK, Peppas NA, Khademhosseini A (2014) Nanocomposite hydrogels for biomedical applications. Biotechnol Bioeng 111(3):441–453

    CrossRef  CAS  PubMed  Google Scholar 

  30. Venkatesan J, Kim S-K (2014) Nano-hydroxyapatite composite biomaterials for bone tissue engineering – a review. J Biomed Nanotechnol 10(10):3124–3140

    CrossRef  CAS  PubMed  Google Scholar 

  31. Shin SR et al (2016) Reduced graphene oxide-gelMA hybrid hydrogels as scaffolds for cardiac tissue engineering. Small 12(27):3677–3689

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shin SR et al (2013) Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators. ACS Nano 7(3):2369–2380

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  33. Huang C-T et al (2017) A graphene–polyurethane composite hydrogel as a potential bioink for 3D bioprinting and differentiation of neural stem cells. J Mater Chem B 5(44):8854–8864

    CrossRef  CAS  PubMed  Google Scholar 

  34. Shin J et al (2017) Three-dimensional electroconductive hyaluronic acid hydrogels incorporated with carbon nanotubes and polypyrrole by catechol-mediated dispersion enhance neurogenesis of human neural stem cells. Biomacromolecules 18(10):3060–3072

    CrossRef  CAS  PubMed  Google Scholar 

  35. Wu J et al (2014) Silver nanoparticle/bacterial cellulose gel membranes for antibacterial wound dressing: investigation in vitro and in vivo. Biomed Mater 9(3):035005

    CrossRef  CAS  PubMed  Google Scholar 

  36. Zhang J, Huang Q, Du J (2016) Recent advances in magnetic hydrogels. Polym Int 65(12):1365–1372

    CrossRef  CAS  Google Scholar 

  37. Kabanov AV, Vinogradov SV (2009) Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. Angew Chem Int Ed 48(30):5418–5429

    CrossRef  CAS  Google Scholar 

  38. Discher DE, Janmey P, Wang Y-L (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310(5751):1139–1143

    CrossRef  CAS  PubMed  Google Scholar 

  39. Klein EA et al (2009) Cell-cycle control by physiological matrix elasticity and in vivo tissue stiffening. Curr Biol 19(18):1511–1518

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pelham RJ, Wang Y-L (1997) Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci 94(25):13661–13665

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kyburz KA, Anseth KS (2013) Three-dimensional hMSC motility within peptide-functionalized PEG-based hydrogels of varying adhesivity and crosslinking density. Acta Biomater 9(5):6381–6392

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  42. Guiseppi-Elie A, Dong C, Dinu CZ (2012) Crosslink density of a biomimetic poly (HEMA)-based hydrogel influences growth and proliferation of attachment dependent RMS 13 cells. J Mater Chem 22(37):19529–19539

    CrossRef  CAS  Google Scholar 

  43. Nicodemus GD, Bryant SJ (2008) Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng Part B Rev 14(2):149–165

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lucke A et al (2000) Biodegradable poly (D, L-lactic acid)-poly (ethylene glycol)-monomethyl ether diblock copolymers: structures and surface properties relevant to their use as biomaterials. Biomaterials 21(23):2361–2370

    CrossRef  CAS  PubMed  Google Scholar 

  45. Sahoo S et al (2008) Hydrolytically degradable hyaluronic acid hydrogels with controlled temporal structures. Biomacromolecules 9(4):1088–1092

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  46. Fonseca KB, Granja PL, Barrias CC (2014) Engineering proteolytically-degradable artificial extracellular matrices. Prog Polym Sci 39(12):2010–2029

    CrossRef  CAS  Google Scholar 

  47. Tauro JR, Gemeinhart RA (2005) Matrix metalloprotease triggered delivery of cancer chemotherapeutics from hydrogel matrixes. Bioconjug Chem 16(5):1133–1139

    CrossRef  CAS  PubMed  Google Scholar 

  48. Patterson J, Hubbell JA (2010) Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2. Biomaterials 31(30):7836–7845

    CrossRef  CAS  PubMed  Google Scholar 

  49. Feng Q et al (2017) Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy. Acta Biomater 53:329–342

    CrossRef  CAS  PubMed  Google Scholar 

  50. Sawhney AS, Pathak CP, Hubbell JA (1993) Bioerodible hydrogels based on photopolymerized poly (ethylene glycol)-co-poly (.alpha.-hydroxy acid) diacrylate macromers. Macromolecules 26(4):581–587

    CrossRef  CAS  Google Scholar 

  51. Rowley JA, Mooney DJ (2002) Alginate type and RGD density control myoblast phenotype. J Biomed Mater Res 60(2):217–223

    CrossRef  CAS  PubMed  Google Scholar 

  52. Park YD, Tirelli N, Hubbell JA (2003) Photopolymerized hyaluronic acid-based hydrogels and interpenetrating networks. Biomaterials 24(6):893–900

    CrossRef  CAS  PubMed  Google Scholar 

  53. Park KM et al (2008) RGD-conjugated chitosan-pluronic hydrogels as a cell supported scaffold for articular cartilage regeneration. Macromol Res 16(6):517–523

    CrossRef  CAS  Google Scholar 

  54. Burdick JA, Anseth KS (2002) Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials 23(22):4315–4323

    CrossRef  CAS  PubMed  Google Scholar 

  55. Schultz GS, Wysocki A (2009) Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 17(2):153–162

    CrossRef  PubMed  Google Scholar 

  56. Nguyen AH et al (2015) Gelatin methacrylate microspheres for controlled growth factor release. Acta Biomater 13:101–110

    CrossRef  CAS  PubMed  Google Scholar 

  57. Goh M, Hwang Y, Tae G (2016) Epidermal growth factor loaded heparin-based hydrogel sheet for skin wound healing. Carbohydr Polym 147:251–260

    CrossRef  CAS  PubMed  Google Scholar 

  58. Zisch AH et al (2003) Cell-demanded release of VEGF from synthetic, biointeractive cell-ingrowth matrices for vascularized tissue growth. FASEB J 17(15):2260–2262

    CrossRef  CAS  PubMed  Google Scholar 

  59. Ward MA, Georgiou TK (2011) Thermoresponsive polymers for biomedical applications. Polymers 3(3):1215–1242

    CrossRef  CAS  Google Scholar 

  60. Shim WS et al (2006) Biodegradability and biocompatibility of a pH-and thermo-sensitive hydrogel formed from a sulfonamide-modified poly (ε-caprolactone-co-lactide)–poly (ethylene glycol)–poly (ε-caprolactone-co-lactide) block copolymer. Biomaterials 27(30):5178–5185

    CrossRef  CAS  PubMed  Google Scholar 

  61. Prabaharan M, Mano JF (2006) Stimuli-responsive hydrogels based on polysaccharides incorporated with thermo-responsive polymers as novel biomaterials. Macromol Biosci 6(12):991–1008

    CrossRef  CAS  PubMed  Google Scholar 

  62. MacEwan SR, Chilkoti A (2010) Elastin-like polypeptides: biomedical applications of tunable biopolymers. Peptide Sci Original Res Biomol 94(1):60–77

    CAS  Google Scholar 

  63. Tang Z, Okano T (2014) Recent development of temperature-responsive surfaces and their application for cell sheet engineering. Regenerative Biomater 1(1):91–102

    CrossRef  Google Scholar 

  64. Klouda L (2015) Thermoresponsive hydrogels in biomedical applications: a seven-year update. Eur J Pharm Biopharm 97:338–349

    CrossRef  CAS  PubMed  Google Scholar 

  65. Klouda L, Mikos AG (2008) Thermoresponsive hydrogels in biomedical applications. Eur J Pharm Biopharm 68(1):34–45

    CrossRef  CAS  PubMed  Google Scholar 

  66. Yang JM, Lin HT (2004) Properties of chitosan containing PP-g-AA-g-NIPAAm bigraft nonwoven fabric for wound dressing. J Membr Sci 243(1–2):1–7

    CAS  Google Scholar 

  67. Priya SG, Jungvid H, Kumar A (2008) Skin tissue engineering for tissue repair and regeneration. Tissue Eng Part B Rev 14(1):105–118

    CrossRef  CAS  PubMed  Google Scholar 

  68. Schmaljohann D (2006) Thermo-and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev 58(15):1655–1670

    CrossRef  CAS  PubMed  Google Scholar 

  69. Kocak G, Tuncer C, Bütün V (2017) pH-responsive polymers. Polym Chem 8(1):144–176

    CrossRef  CAS  Google Scholar 

  70. Xu L et al (2018) Biodegradable pH-responsive hydrogels for controlled dual-drug release. J Mater Chem B 6(3):510–517

    CrossRef  CAS  PubMed  Google Scholar 

  71. Knipe JM, Chen F, Peppas NA (2015) Enzymatic biodegradation of hydrogels for protein delivery targeted to the small intestine. Biomacromolecules 16(3):962–972

    CrossRef  CAS  PubMed  Google Scholar 

  72. Curcio M et al (2013) Biodegradable gelatin-based nanospheres as pH-responsive drug delivery systems. J Nanopart Res 15(4):1–11

    CrossRef  CAS  Google Scholar 

  73. Popat A et al (2012) A pH-responsive drug delivery system based on chitosan coated mesoporous silica nanoparticles. J Mater Chem 22(22):11173–11178

    CrossRef  CAS  Google Scholar 

  74. Chan AW, Neufeld RJ (2009) Modeling the controllable pH-responsive swelling and pore size of networked alginate based biomaterials. Biomaterials 30(30):6119–6129

    CrossRef  CAS  PubMed  Google Scholar 

  75. Gu Z et al (2013) Glucose-responsive microgels integrated with enzyme nanocapsules for closed-loop insulin delivery. ACS Nano 7(8):6758–6766

    CrossRef  CAS  PubMed  Google Scholar 

  76. Peppas NA, Van Blarcom DS (2016) Hydrogel-based biosensors and sensing devices for drug delivery. J Control Release 240:142–150

    CrossRef  CAS  PubMed  Google Scholar 

  77. Park JY et al (2006) A polymeric microfluidic valve employing a pH-responsive hydrogel microsphere as an actuating source. J Micromech Microeng 16(3):656

    CrossRef  Google Scholar 

  78. Li L, Scheiger JM, Levkin PA (2019) Design and applications of photoresponsive hydrogels. Adv Mater 31(26):1807333

    CrossRef  CAS  Google Scholar 

  79. ter Schiphorst J et al (2015) Molecular design of light-responsive hydrogels, for in situ generation of fast and reversible valves for microfluidic applications. Chem Mater 27(17):5925–5931

    CrossRef  CAS  Google Scholar 

  80. Prasad PN (2003) Introduction to biophotonics. Wiley, Hoboken

    CrossRef  Google Scholar 

  81. Zhang H et al (2017) A near-infrared light-responsive hybrid hydrogel based on UCST triblock copolymer and gold nanorods. Polymers 9(6):238

    CrossRef  PubMed Central  CAS  Google Scholar 

  82. Zhou M et al (2015) Doxorubicin-loaded single wall nanotube thermo-sensitive hydrogel for gastric cancer chemo-photothermal therapy. Adv Funct Mater 25(29):4730–4739

    CrossRef  CAS  Google Scholar 

  83. Chang R, Tsai W-B (2018) Fabrication of photothermo-responsive drug-loaded nanogel for synergetic cancer therapy. Polymers 10(10):1098

    CrossRef  PubMed Central  CAS  Google Scholar 

  84. Qiu M et al (2018) Novel concept of the smart NIR-light–controlled drug release of black phosphorus nanostructure for cancer therapy. Proc Natl Acad Sci 115(3):501–506

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  85. Rosales AM et al (2017) Hydrogels with reversible mechanics to probe dynamic cell microenvironments. Angew Chem Int Ed 56(40):12132–12136

    CrossRef  CAS  Google Scholar 

  86. DeForest CA, Tirrell DA (2015) A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels. Nat Mater 14(5):523–531

    CrossRef  CAS  PubMed  Google Scholar 

  87. Wang R et al (2017) B12-dependent photoresponsive protein hydrogels for controlled stem cell/protein release. Proc Natl Acad Sci 114(23):5912–5917

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  88. Li F et al (2020) DNA hydrogels and microgels for biosensing and biomedical applications. Adv Mater 32(3):1806538

    CrossRef  CAS  Google Scholar 

  89. Liu J (2011) Oligonucleotide-functionalized hydrogels as stimuli responsive materials and biosensors. Soft Matter 7(15):6757–6767

    CrossRef  CAS  Google Scholar 

  90. Geraths C et al (2013) A biohybrid hydrogel for the urate-responsive release of urate oxidase. J Control Release 171(1):57–62

    CrossRef  CAS  PubMed  Google Scholar 

  91. Byrne ME, Park K, Peppas NA (2002) Molecular imprinting within hydrogels. Adv Drug Deliv Rev 54(1):149–161

    CrossRef  CAS  PubMed  Google Scholar 

  92. Parmpi P, Kofinas P (2004) Biomimetic glucose recognition using molecularly imprinted polymer hydrogels. Biomaterials 25(10):1969–1973

    CrossRef  CAS  PubMed  Google Scholar 

  93. Singh B, Chauhan N (2008) Preliminary evaluation of molecular imprinting of 5-fluorouracil within hydrogels for use as drug delivery systems. Acta Biomater 4(5):1244–1254

    CrossRef  CAS  PubMed  Google Scholar 

  94. Verheyen E et al (2011) Challenges for the effective molecular imprinting of proteins. Biomaterials 32(11):3008–3020

    CrossRef  CAS  PubMed  Google Scholar 

  95. Adedoyin AA, Ekenseair AK (2018) Biomedical applications of magneto-responsive scaffolds. Nano Res 11(10):5049–5064

    CrossRef  CAS  Google Scholar 

  96. Fuhrer R et al (2009) Crosslinking metal nanoparticles into the polymer backbone of hydrogels enables preparation of soft, magnetic field-driven actuators with muscle-like flexibility. Small 5(3):383–388

    CrossRef  CAS  PubMed  Google Scholar 

  97. Zhao X et al (2011) Active scaffolds for on-demand drug and cell delivery. Proc Natl Acad Sci 108(1):67–72

    CrossRef  CAS  PubMed  Google Scholar 

  98. Xie W et al (2017) Injectable and self-healing thermosensitive magnetic hydrogel for asynchronous control release of doxorubicin and docetaxel to treat triple-negative breast cancer. ACS Appl Mater Interfaces 9(39):33660–33673

    CrossRef  CAS  PubMed  Google Scholar 

  99. Meenach SA et al (2013) Characterization of PEG–iron oxide hydrogel nanocomposites for dual hyperthermia and paclitaxel delivery. J Biomater Sci Polym Ed 24(9):1112–1126

    CrossRef  CAS  PubMed  Google Scholar 

  100. Liu Z et al (2020) Recent advances on magnetic sensitive hydrogels in tissue engineering. Front Chem 8

    Google Scholar 

  101. Fuhrer R et al (2013) Pressureless mechanical induction of stem cell differentiation is dose and frequency dependent. PLoS One 8(11):e81362

    CrossRef  PubMed  PubMed Central  CAS  Google Scholar 

  102. Meng J et al (2013) Super-paramagnetic responsive nanofibrous scaffolds under static magnetic field enhance osteogenesis for bone repair in vivo. Sci Rep 3(1):1–7

    CrossRef  Google Scholar 

  103. Antman-Passig M, Shefi O (2016) Remote magnetic orientation of 3D collagen hydrogels for directed neuronal regeneration. Nano Lett 16(4):2567–2573

    CrossRef  CAS  PubMed  Google Scholar 

  104. Lacko CS et al (2020) Magnetic particle templating of hydrogels: engineering naturally derived hydrogel scaffolds with 3D aligned microarchitecture for nerve repair. J Neural Eng 17(1):016057

    CrossRef  PubMed  PubMed Central  Google Scholar 

  105. Margolis G, Polyak B, Cohen S (2018) Magnetic induction of multiscale anisotropy in macroporous alginate scaffolds. Nano Lett 18(11):7314–7322

    CrossRef  CAS  PubMed  Google Scholar 

  106. Murdan S (2003) Electro-responsive drug delivery from hydrogels. J Control Release 92(1–2):1–17

    CrossRef  CAS  PubMed  Google Scholar 

  107. Ding M et al (2020) Multifunctional soft machines based on stimuli-responsive hydrogels: from freestanding hydrogels to smart integrated systems. Mater Today Adv 8:100088

    CrossRef  Google Scholar 

  108. Erol O et al (2019) Transformer hydrogels: a review. Adv Mater Technol 4(4):1900043

    CrossRef  CAS  Google Scholar 

  109. Xue B et al (2016) Electrically controllable actuators based on supramolecular peptide hydrogels. Adv Funct Mater 26(48):9053–9062

    CrossRef  CAS  Google Scholar 

  110. Park N, Kim J (2020) Hydrogel-based artificial muscles: overview and recent progress. Adv Intelligent Syst 2(4):1900135

    CrossRef  Google Scholar 

  111. Kulkarni RV, Setty CM, Sa B (2010) Polyacrylamide-g-alginate-based electrically responsive hydrogel for drug delivery application: synthesis, characterization, and formulation development. J Appl Polym Sci 115(2):1180–1188

    CrossRef  CAS  Google Scholar 

  112. Ying X et al (2014) Angiopep-conjugated electro-responsive hydrogel nanoparticles: therapeutic potential for epilepsy. Angew Chem 126(46):12644–12648

    CrossRef  Google Scholar 

  113. Guiseppi-Elie A (2010) Electroconductive hydrogels: synthesis, characterization and biomedical applications. Biomaterials 31(10):2701–2716

    CrossRef  CAS  PubMed  Google Scholar 

  114. Lu H, Zhang N, Ma M (2019) Electroconductive hydrogels for biomedical applications. Wiley Interdiscip Rev Nanomed Nanobiotechnol 11(6):e1568

    CrossRef  PubMed  Google Scholar 

  115. Ge J et al (2012) Drug release from electric-field-responsive nanoparticles. ACS Nano 6(1):227–233

    CrossRef  CAS  PubMed  Google Scholar 

  116. Chandan R, Mehta S, Banerjee R (2020) Ultrasound-responsive carriers for therapeutic applications. ACS Biomater Sci Eng 6(9):4731–4747

    CrossRef  CAS  PubMed  Google Scholar 

  117. Bhatnagar S et al (2016) Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines. J Control Release 238:22–30

    CrossRef  CAS  PubMed  Google Scholar 

  118. Fabiilli ML et al (2013) Acoustic droplet–hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness. Acta Biomater 9(7):7399–7409

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  119. Jin H et al (2012) Ultrasound-triggered thrombolysis using urokinase-loaded nanogels. Int J Pharm 434(1–2):384–390

    CrossRef  CAS  PubMed  Google Scholar 

  120. Yamaguchi S et al (2019) Supramolecular polymeric hydrogels for ultrasound-guided protein release. Biotechnol J 14(5):1800530

    CrossRef  CAS  Google Scholar 

  121. Sun W et al (2019) Strong dual-crosslinked hydrogels for ultrasound-triggered drug delivery. Nano Res 12(1):115–119

    CrossRef  CAS  Google Scholar 

  122. Lima EG et al (2012) Microbubbles as biocompatible porogens for hydrogel scaffolds. Acta Biomater 8(12):4334–4341

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  123. Aliabouzar M, Zhang LG, Sarkar K (2016) Lipid coated microbubbles and low intensity pulsed ultrasound enhance chondrogenesis of human mesenchymal stem cells in 3D printed scaffolds. Sci Rep 6(1):1–11

    CrossRef  CAS  Google Scholar 

  124. Nomikou N et al (2018) Ultrasound-responsive gene-activated matrices for osteogenic gene therapy using matrix-assisted sonoporation. J Tissue Eng Regen Med 12(1):e250–e260

    CrossRef  CAS  PubMed  Google Scholar 

  125. Guo X et al (2018) Advances in redox-responsive drug delivery systems of tumor microenvironment. J Nanobiotechnol 16(1):1–10

    CrossRef  CAS  Google Scholar 

  126. Pan Y-J et al (2012) Redox/pH dual stimuli-responsive biodegradable nanohydrogels with varying responses to dithiothreitol and glutathione for controlled drug release. Biomaterials 33(27):6570–6579

    CrossRef  CAS  PubMed  Google Scholar 

  127. Yan Y et al (2010) Uptake and intracellular fate of disulfide-bonded polymer hydrogel capsules for doxorubicin delivery to colorectal cancer cells. ACS Nano 4(5):2928–2936

    CrossRef  CAS  PubMed  Google Scholar 

  128. Li J et al (2015) Self-assembly of DNA nanohydrogels with controllable size and stimuli-responsive property for targeted gene regulation therapy. J Am Chem Soc 137(4):1412–1415

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  129. Kar M et al (2016) Poly (ethylene glycol) hydrogels with cell cleavable groups for autonomous cell delivery. Biomaterials 77:186–197

    CrossRef  CAS  PubMed  Google Scholar 

  130. Ravaine V, Ancla C, Catargi B (2008) Chemically controlled closed-loop insulin delivery. J Control Release 132(1):2–11

    CrossRef  CAS  PubMed  Google Scholar 

  131. Traitel T, Cohen Y, Kost J (2000) Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions. Biomaterials 21(16):1679–1687

    CrossRef  CAS  PubMed  Google Scholar 

  132. Tanna S et al (2006) The effect of degree of acrylic derivatisation on dextran and concanavalin A glucose-responsive materials for closed-loop insulin delivery. Biomaterials 27(25):4498–4507

    CrossRef  CAS  PubMed  Google Scholar 

  133. Kataoka K et al (1998) Totally synthetic polymer gels responding to external glucose concentration: their preparation and application to on− off regulation of insulin release. J Am Chem Soc 120(48):12694–12695

    CrossRef  CAS  Google Scholar 

  134. Matsumoto A et al (2010) A totally synthetic glucose responsive gel operating in physiological aqueous conditions. Chem Commun 46(13):2203–2205

    CrossRef  CAS  Google Scholar 

  135. Yesilyurt V et al (2016) Injectable self-healing glucose-responsive hydrogels with pH-regulated mechanical properties. Adv Mater 28(1):86–91

    CrossRef  CAS  PubMed  Google Scholar 

  136. Zhao F et al (2017) An injectable particle-hydrogel hybrid system for glucose-regulatory insulin delivery. Acta Biomater 64:334–345

    CrossRef  CAS  PubMed  Google Scholar 

  137. Tu Y et al (2019) Advances in injectable self-healing biomedical hydrogels. Acta Biomater 90:1–20

    CrossRef  CAS  PubMed  Google Scholar 

  138. Saunders L, Ma PX (2019) Self-healing supramolecular hydrogels for tissue engineering applications. Macromol Biosci 19(1):1800313

    CrossRef  CAS  Google Scholar 

  139. Talebian S et al (2019) Self-healing hydrogels: the next paradigm shift in tissue engineering? Adv Sci 6(16):1801664

    CrossRef  CAS  Google Scholar 

  140. Taylor DL, M. in het Panhuis (2016) Self-healing hydrogels. Adv Mater 28(41):9060–9093

    CrossRef  CAS  PubMed  Google Scholar 

  141. Qu J et al (2017) pH-responsive self-healing injectable hydrogel based on N-carboxyethyl chitosan for hepatocellular carcinoma therapy. Acta Biomater 58:168–180

    CrossRef  CAS  PubMed  Google Scholar 

  142. Nakahata M et al (2011) Redox-responsive self-healing materials formed from host–guest polymers. Nat Commun 2(1):1–6

    CrossRef  CAS  Google Scholar 

  143. Guvendiren M, Lu HD, Burdick JA (2012) Shear-thinning hydrogels for biomedical applications. Soft Matter 8(2):260–272

    CrossRef  CAS  Google Scholar 

  144. Highley CB, Rodell CB, Burdick JA (2015) Direct 3D printing of shear-thinning hydrogels into self-healing hydrogels. Adv Mater 27(34):5075–5079

    CrossRef  CAS  PubMed  Google Scholar 

  145. Nejadnik MR et al (2014) Self-healing hybrid nanocomposites consisting of bisphosphonated hyaluronan and calcium phosphate nanoparticles. Biomaterials 35(25):6918–6929

    CrossRef  CAS  PubMed  Google Scholar 

  146. Hou S et al (2015) Rapid self-integrating, injectable hydrogel for tissue complex regeneration. Adv Healthc Mater 4(10):1491–1495

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  147. Gaffey AC et al (2015) Injectable shear-thinning hydrogels used to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium. J Thorac Cardiovasc Surg 150(5):1268–1277

    CrossRef  PubMed  PubMed Central  Google Scholar 

  148. McKinnon DD et al (2014) Biophysically defined and cytocompatible covalently adaptable networks as viscoelastic 3D cell culture systems. Adv Mater 26(6):865–872

    CrossRef  CAS  PubMed  Google Scholar 

  149. Tseng TC et al (2015) An injectable, self-healing hydrogel to repair the central nervous system. Adv Mater 27(23):3518–3524

    CrossRef  CAS  PubMed  Google Scholar 

  150. Tseng T-C et al (2017) Glucose-sensitive self-healing hydrogel as sacrificial materials to fabricate vascularized constructs. Biomaterials 133:20–28

    CrossRef  CAS  PubMed  Google Scholar 

  151. Zhao X et al (2017) Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing. Biomaterials 122:34–47

    CrossRef  CAS  PubMed  Google Scholar 

  152. Phadke A et al (2012) Rapid self-healing hydrogels. Proc Natl Acad Sci 109(12):4383–4388

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  153. Kirschner CM, Anseth KS (2013) Hydrogels in healthcare: from static to dynamic material microenvironments. Acta Mater 61(3):931–944

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  154. Arkenberg MR, Nguyen HD, Lin C-C (2020) Recent advances in bio-orthogonal and dynamic crosslinking of biomimetic hydrogels. J Mater Chem B 8(35):7835–7855

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  155. Vedadghavami A et al (2017) Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications. Acta Biomater 62:42–63

    CrossRef  CAS  PubMed  Google Scholar 

  156. Ikeda M et al (2014) Installing logic-gate responses to a variety of biological substances in supramolecular hydrogel–enzyme hybrids. Nat Chem 6(6):511–518

    CrossRef  CAS  PubMed  Google Scholar 

  157. Badeau BA et al (2018) Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery. Nat Chem 10(3):251

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  158. Williams DF (2019) Challenges with the development of biomaterials for sustainable tissue engineering. Front Bioeng Biotechnol 7:127

    CrossRef  PubMed  PubMed Central  Google Scholar 

  159. Li J, Mooney DJ (2016) Designing hydrogels for controlled drug delivery. Nat Rev Mater 1(12):1–17

    CrossRef  CAS  Google Scholar 

  160. Sonmez C, Nagy KJ, Schneider JP (2015) Design of self-assembling peptide hydrogelators amenable to bacterial expression. Biomaterials 37:62–72

    CrossRef  CAS  PubMed  Google Scholar 

  161. Morais JM, Papadimitrakopoulos F, Burgess DJ (2010) Biomaterials/tissue interactions: possible solutions to overcome foreign body response. AAPS J 12(2):188–196

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  162. Othman SF, Xu H, Mao JJ (2015) Future role of MR elastography in tissue engineering and regenerative medicine. J Tissue Eng Regen Med 9(5):481–487

    CrossRef  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Iliyana Pepelanova .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pepelanova, I. (2021). Tunable Hydrogels: Introduction to the World of Smart Materials for Biomedical Applications. In: Lavrentieva, A., Pepelanova, I., Seliktar, D. (eds) Tunable Hydrogels. Advances in Biochemical Engineering/Biotechnology, vol 178. Springer, Cham. https://doi.org/10.1007/10_2021_168

Download citation