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Advances in self-healing hydrogels to repair tissue defects

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Abstract

In modern times, biological materials have received a lot of attention due to their potentials in the treatment of body defects. Among biomaterials, hydrogels have a high advantage due to their multifunctional structures and behavior. However, the mechanical failure of conventional hydrogels under normal conditions remains a significant problem. To overcome this lesion, self-healing hydrogel materials have been created that have the property of self-healing and are minimally invasive for repairing biological defects in the whole body. In this review study, by combining the developments of recent articles in synthesis and discussion of clinical applications for repairing various types of body defects, the development of self-healing hydrogels is presented. By reviewing the characteristics and behaviors of healable hydrogels, the repair of different types of defects as well as their mechanism is presented. Some properties of polymers such as molecular mass, hydrophilicity, functional groups, intramolecular and extramolecular interactions can affect the properties of self-healing hydrogels. The review examines the development of smart self-healing hydrogel processes over the past 10 years, focusing primarily on their recent ability to repair tissue defects. This paper also presents various methods of synthesis and types of polymers and discusses clinical applications that facilitate the improvement of lesions and enhance organs function. The issues presented here may be of interest to researchers interested in improving self-healing hydrogels.

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References

  1. Li S, Yi J, Yu X et al (2018) Preparation and characterization of acid resistant double cross-linked hydrogel for potential biomedical applications. ACS Biomater Sci Eng 4:872–883

    Article  CAS  Google Scholar 

  2. Xu R, Ma S, Lin P et al (2018) High strength astringent hydrogels using protein as the building block for physically cross-linked multi-network. ACS Appl Mater Interfaces 10:7593–7601

    Article  CAS  Google Scholar 

  3. Wang H, Heilshorn SC (2015) Adaptable hydrogel networks with reversible linkages for tissue engineering. Adv Mater 27:3717–3736

    Article  CAS  Google Scholar 

  4. Webber MJ, Appel EA, Meijer EW, Langer R (2016) Supramolecular biomaterials. Nat Mater 15:13–26

    Article  CAS  Google Scholar 

  5. Luo K, Yang Y, Shao Z (2016) Physically crosslinked biocompatible silk-fibroin-based hydrogels with high mechanical performance. Adv Funct Mater 26:872–880

    Article  CAS  Google Scholar 

  6. Loh XJ, Peh P, Liao S et al (2010) Controlled drug release from biodegradable thermoresponsive physical hydrogel nanofibers. J Control Release 143:175–182

    Article  CAS  Google Scholar 

  7. Zhu P, Hu M, Deng Y, Wang C (2016) One-pot fabrication of a novel agar-polyacrylamide/graphene oxide nanocomposite double network hydrogel with high mechanical properties. Adv Eng Mater 18:1799–1807

    Article  CAS  Google Scholar 

  8. Jia H, Li Z, Wang X, Zheng Z (2015) Facile functionalization of a tetrahedron-like PEG macromonomer-based fluorescent hydrogel with high strength and its heavy metal ion detection. J Mater Chem A 3:1158–1163

    Article  CAS  Google Scholar 

  9. Ha W, Yu J, Song XY et al (2014) Tunable temperature-responsive supramolecular hydrogels formed by prodrugs as a codelivery system. ACS Appl Mater Interfaces 6:10623–10630

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Yin M-J, Yao M, Gao S et al (2016) Rapid 3D patterning of poly(acrylic acid) ionic hydrogel for miniature pH sensors. Adv Mater 28:1394–1399

    Article  CAS  Google Scholar 

  14. Sun J-Y, Zhao X, Illeperuma WRK et al (2012) Highly stretchable and tough hydrogels. Nature 489:133–136

    Article  CAS  Google Scholar 

  15. Deng Z, Guo Y, Zhao X et al (2018) Multifunctional stimuli-responsive hydrogels with self-healing, high conductivity and rapid recovery through host-guest interactions. Chem Mater 30:1729–1742

    Article  CAS  Google Scholar 

  16. Yuan N, Xu L, Wang H et al (2016) Dual physically cross-linked double network hydrogels with high mechanical strength, fatigue resistance, notch-insensitivity and self-healing properties. ACS Appl Mater Interfaces 8:34034–34044

    Article  CAS  Google Scholar 

  17. Yan X, Chen Q, Zhu L et al (2017) High strength and self-healable gelatin/polyacrylamide double network hydrogels. J Mater Chem B 5:7683–7691

    Article  CAS  Google Scholar 

  18. Qin Y, Wang J, Qiu C et al (2019) A dual cross-linked strategy to construct moldable hydrogels with high stretchability, good self-recovery and self-healing capability. J Agric Food Chem 67:3966–3980

    Article  CAS  Google Scholar 

  19. Yang Y, Urban MW (2013) Self-healing polymeric materials. Chem Soc Rev 42:7446

    Article  CAS  Google Scholar 

  20. Wang W, Zhang Y, Liu W (2017) Bioinspired fabrication of high strength hydrogels from non-covalent interactions. Prog Polym Sci 71:1–25

    Article  Google Scholar 

  21. Guo Y, Bae J, Fang Z et al (2020) Hydrogels and hydrogel-derived materials for energy and water sustainability. Chem Rev 120:7642–7707

    Article  CAS  Google Scholar 

  22. Rauner N, Meuris M, Zoric M, Tiller JC (2017) Enzymatic mineralization generates ultrastiff and tough hydrogels with tunable mechanics. Nature 543:407–410

    Article  CAS  Google Scholar 

  23. Zhang J, Zhu Y, Song J et al (2018) Novel balanced charged alginate/pei polyelectrolyte hydrogel that resists foreign-body reaction. ACS Appl Mater Interfaces 10:6879–6886

    Article  CAS  Google Scholar 

  24. González-Domínguez JM, Martín C, Durá ÓJ et al (2018) Smart hybrid graphene hydrogels: a study of the different responses to mechanical stretching stimulus. ACS Appl Mater Interfaces 10:1987–1995

    Article  Google Scholar 

  25. Jeon O, Shin JY, Marks R et al (2017) Highly elastic and tough interpenetrating polymer network-structured hybrid hydrogels for cyclic mechanical loading-enhanced tissue engineering. Chem Mater 29:8425–8432

    Article  CAS  Google Scholar 

  26. Gong JP, Katsuyama Y, Kurokawa T, Osada Y (2003) Double-network hydrogels with extremely high mechanical strength. Adv Mater 15:1155–1158

    Article  CAS  Google Scholar 

  27. Gong JP (2014) Materials both tough and soft. Science 344:161–162

    Article  CAS  Google Scholar 

  28. Iriyanov YM, Chernov VF, Radchenko SA, Chernov AV (2013) Plastic efficiency of different implants used for repair of soft and bone tissue defects. Bull Exp Biol Med 155:518–521

    Article  CAS  Google Scholar 

  29. Tu Y, Chen N, Li C et al (2019) Advances in injectable self-healing biomedical hydrogels. Acta Biomater 90:1–20

    Article  CAS  Google Scholar 

  30. Zhang Y, Li Y, Liu W (2015) Dipole-dipole and h-bonding interactions significantly enhance the multifaceted mechanical properties of thermoresponsive shape memory hydrogels. Adv Funct Mater 25:471–480

    Article  CAS  Google Scholar 

  31. Chen H, Chen Q, Hu R et al (2015) Mechanically strong hybrid double network hydrogels with antifouling properties. J Mater Chem B 3:5426–5435

    Article  CAS  Google Scholar 

  32. Chen Q, Wei D, Chen H et al (2015) Simultaneous enhancement of stiffness and toughness in hybrid double-network hydrogels via the first, physically linked network. Macromolecules 48:8003–8010

    Article  CAS  Google Scholar 

  33. Wang Y, Niu J, Hou J et al (2018) A novel design strategy for triple-network structure hydrogels with high-strength, tough and self-healing properties. Polymer 135:16–24

    Article  CAS  Google Scholar 

  34. Liu S, Li L (2016) Recoverable and self-healing double network hydrogel based on κ-carrageenan. ACS Appl Mater Interfaces 8:29749–29758

    Article  CAS  Google Scholar 

  35. Chen WP, Hao DZ, Hao WJ et al (2018) Hydrogel with ultrafast self-healing property both in air and underwater. ACS Appl Mater Interfaces 10:1258–1265

    Article  CAS  Google Scholar 

  36. De France KJ, Hoare T, Cranston ED (2017) Review of hydrogels and aerogels containing nanocellulose. Chem Mater 29:4609–4631

    Article  Google Scholar 

  37. Azevedo S, Costa AMS, Andersen A et al (2017) Bioinspired ultratough hydrogel with fast recovery, self-healing, injectability and cytocompatibility. Adv Mater 29:1–6

    Article  Google Scholar 

  38. Upadhyay A, Kandi R, Rao CP (2018) Injectable, self-healing, and stress sustainable hydrogel of BSA as a functional biocompatible material for controlled drug delivery in cancer cells. ACS Sustain Chem Eng 6:3321–3330

    Article  CAS  Google Scholar 

  39. Lima-Tenório MK, Tenório-Neto ET, Guilherme MR et al (2015) Water transport properties through starch-based hydrogel nanocomposites responding to both pH and a remote magnetic field. Chem Eng J 259:620–629

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  41. Lin HL, Liu YF, Yu TL et al (2005) Light scattering and viscoelasticity study of poly(vinyl alcohol)-borax aqueous solutions and gels. Polymer 46:5541–5549

    Article  CAS  Google Scholar 

  42. Bagri LP, Bajpai J, Bajpai AK (2009) Cryogenic designing of biocompatible blends of polyvinyl alcohol and starch with macroporous architecture. J Macromol Sci Part A Pure Appl Chem 46:1060–1068

    Article  CAS  Google Scholar 

  43. Follain N, Joly C, Dole P, Bliard C (2005) Properties of starch based blends. Part 2. Influence of poly vinyl alcohol addition and photocrosslinking on starch based materials mechanical properties. Carbohydr Polym 60:185–192

    Article  CAS  Google Scholar 

  44. Sreedhar B, Chattopadhyay DK, Karunakar MSH, Sastry ARK (2006) Thermal and surface characterization of plasticized starch polyvinyl alcohol blends crosslinked with epichlorohydrin. J Appl Polym Sci 101:25–34

    Article  CAS  Google Scholar 

  45. Sreedhar B, Sairam M, Chattopadhyay DK et al (2005) Thermal, mechanical and surface characterization of starch-poly(vinyl alcohol) blends and borax-crosslinked films. J Appl Polym Sci 96:1313–1322

    Article  CAS  Google Scholar 

  46. Bursali EA, Coskun S, Kizil M, Yurdakoc M (2011) Synthesis, characterization and in vitro antimicrobial activities of boron/starch/polyvinyl alcohol hydrogels. Carbohydr Polym 83:1377–1383

    Article  CAS  Google Scholar 

  47. Zhang T, Zuo T, Hu D, Chang C (2017) Dual physically cross-linked nanocomposite hydrogels reinforced by tunicate cellulose nanocrystals with high toughness and good self-recoverability. ACS Appl Mater Interfaces 9:24230–24237

    Article  CAS  Google Scholar 

  48. Yu HC, Zhang H, Ren K et al (2018) Ultrathin κ-carrageenan/chitosan hydrogel films with high toughness and antiadhesion property. ACS Appl Mater Interfaces 10:9002–9009

    Article  CAS  Google Scholar 

  49. Yang J, Xu F, Han CR (2017) Metal ion mediated cellulose nanofibrils transient network in covalently cross-linked hydrogels: mechanistic insight into morphology and dynamics. Biomacromolecules 18:1019–1028

    Article  CAS  Google Scholar 

  50. Chen H, Liu Y, Ren B et al (2017) Super bulk and interfacial toughness of physically crosslinked double-network hydrogels. Adv Funct Mater 27:1–10

    Article  Google Scholar 

  51. Ji N, Qin Y, Li M et al (2018) Fabrication and characterization of starch nanohydrogels via reverse emulsification and internal gelation. J Agric Food Chem 66:9326–9334

    Article  CAS  Google Scholar 

  52. Torres O, Tena NM, Murray B, Sarkar A (2017) Novel starch based emulsion gels and emulsion microgel particles: design, structure and rheology. Carbohydr Polym 178:86–94

    Article  CAS  Google Scholar 

  53. Chen YN, Peng L, Liu T et al (2016) Poly(vinyl alcohol)-tannic acid hydrogels with excellent mechanical properties and shape memory behaviors. ACS Appl Mater Interfaces 8:27199–27206

    Article  CAS  Google Scholar 

  54. Lu B, Lin F, Jiang X et al (2017) One-pot assembly of microfibrillated cellulose reinforced pva-borax hydrogels with self-healing and ph-responsive properties. ACS Sustain Chem Eng 5:948–956

    Article  CAS  Google Scholar 

  55. Narita T, Indei T (2016) Microrheological study of physical gelation in living polymeric networks. Macromolecules 49:4634–4646

    Article  CAS  Google Scholar 

  56. Qu J, Zhao X, Liang Y et al (2018) Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility and compressibility as wound dressing for joints skin wound healing. Biomaterials 183:185–199

    Article  CAS  Google Scholar 

  57. He J, Wang W, Shi R et al (2018) High speed water purification and efficient phosphate rejection by active nanofibrous membrane for microbial contamination and regrowth control. Chem Eng J 337:428–435

    Article  CAS  Google Scholar 

  58. Balitaan JNI, Der HC, Yeh JM, Santiago KS (2020) Innovation inspired by nature: Biocompatible self-healing injectable hydrogels based on modified-β-chitin for wound healing. Int J Biol Macromol 162:723–736

    Article  CAS  Google Scholar 

  59. Li J, Yu F, Chen G et al (2020) Moist-retaining, self-recoverable, bioadhesive, and transparent in situ forming hydrogels to accelerate wound healing. ACS Appl Mater Interfaces 12:2023–2038

    Article  CAS  Google Scholar 

  60. Chen T, Chen Y, Rehman HU et al (2018) Ultratough, self-healing, and tissue-adhesive hydrogel for wound dressing. ACS Appl Mater Interfaces 10:33523–33531

    Article  CAS  Google Scholar 

  61. Wang C, Wang M, Xu T et al (2019) Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration. Theranostics 9:65–76

    Article  CAS  Google Scholar 

  62. Chen H, Cheng J, Ran L et al (2018) An injectable self-healing hydrogel with adhesive and antibacterial properties effectively promotes wound healing. Carbohydr Polym 201:522–531

    Article  CAS  Google Scholar 

  63. Chen G, Ren J, Deng Y et al (2017) An injectable, wound-adapting, self-healing hydrogel for fibroblast growth factor 2 delivery system in tissue repair applications. J Biomed Nanotechnol 13:1660–1672

    Article  CAS  Google Scholar 

  64. Han L, Zhang Y, Lu X et al (2016) Polydopamine nanoparticles modulating stimuli-responsive PNIPAM hydrogels with cell/tissue adhesiveness. ACS Appl Mater Interfaces 8:29088–29100

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  66. Yan S, Wang W, Li X et al (2018) Preparation of mussel-inspired injectable hydrogels based on dual-functionalized alginate with improved adhesive, self-healing, and mechanical properties. J Mater Chem B 6:6377–6390

    Article  CAS  Google Scholar 

  67. You B, Li Q, Dong H et al (2018) Bilayered HA/CS/PEGDA hydrogel with good biocompatibility and self-healing property for potential application in osteochondral defect repair. J Mater Sci Technol 34:1016–1025

    Article  CAS  Google Scholar 

  68. Ma L, Su W, Ran Y et al (2020) Synthesis and characterization of injectable self-healing hydrogels based on oxidized alginate-hybrid-hydroxyapatite nanoparticles and carboxymethyl chitosan. Int J Biol Macromol 165:1164–1174

    Article  CAS  Google Scholar 

  69. Li P, Liu S, Yang X et al (2021) Low-drug resistance carbon quantum dots decorated injectable self-healing hydrogel with potent antibiofilm property and cutaneous wound healing. Chem Eng J 403:126387

    Article  CAS  Google Scholar 

  70. Lu W, Bao D, Ta F et al (2020) Multifunctional alginate hydrogel protects and heals skin defects in complex clinical situations. ACS Omega 5:17152–17159

    Article  CAS  Google Scholar 

  71. Basu S, Pacelli S, Paul A (2020) Self-healing DNA-based injectable hydrogels with reversible covalent linkages for controlled drug delivery. Acta Biomater 105:159–169

    Article  CAS  Google Scholar 

  72. Sun Q, Li G, Dai L et al (2014) Green preparation and characterisation of waxy maize starch nanoparticles through enzymolysis and recrystallisation. Food Chem 162:223–228

    Article  CAS  Google Scholar 

  73. Qin Y, Liu C, Jiang S et al (2016) Characterization of starch nanoparticles prepared by nanoprecipitation: Influence of amylose content and starch type. Ind Crops Prod 87:182–190

    Article  CAS  Google Scholar 

  74. Taleb MFA, El-Mohdy HLA, El-Rehim HAA (2009) Radiation preparation of PVA/CMC copolymers and their application in removal of dyes. J Hazard Mater 168:68–75

    Article  Google Scholar 

  75. Manna U, Patil S (2009) Borax mediated layer-by-layer self-assembly of neutral poly(vinyl alcohol) and chitosan. J Phys Chem B 113:9137–9142

    Article  CAS  Google Scholar 

  76. Han J, Yue Y, Wu Q et al (2017) Effects of nanocellulose on the structure and properties of poly(vinyl alcohol)-borax hybrid foams. Cellulose 24:4433–4448

    Article  CAS  Google Scholar 

  77. Liu G, Gu Z, Hong Y et al (2017) Structure, functionality and applications of debranched starch: a review. Trends Food Sci Technol 63:70–79

    Article  CAS  Google Scholar 

  78. Peng M, Xiao G, Tang X, Zhou Y (2014) Hydrogen-bonding assembly of rigid-rod poly(p-sulfophenylene terephthalamide) and flexible-chain poly(vinyl alcohol) for transparent, strong, and tough molecular composites. Macromolecules 47:8411–8419

    Article  CAS  Google Scholar 

  79. Zhao Y, Nakajima T, Yang JJ et al (2014) Proteoglycans and glycosaminoglycans improve toughness of biocompatible double network hydrogels. Adv Mater 26:436–442

    Article  Google Scholar 

  80. Zhao D, Huang J, Zhong Y et al (2016) Correction to: high-strength and high-toughness double-cross-linked cellulose hydrogels: a new strategy using sequential chemical and physical cross-linking. Adv Funct Mater 26(34):6279–6287. https://doi.org/10.1002/adfm.201601645)

    Article  CAS  Google Scholar 

  81. Hu X, Feng L, Xie A et al (2014) Synthesis and characterization of a novel hydrogel: salecan/polyacrylamide semi-IPN hydrogel with a desirable pore structure. J Mater Chem B 2:3646–3658

    Article  CAS  Google Scholar 

  82. Zhu B, Ma D, Wang J, Zhang S (2015) Structure and properties of semi-interpenetrating network hydrogel based on starch. Carbohydr Polym 133:448–455

    Article  CAS  Google Scholar 

  83. Feng W, Zhou W, Dai Z et al (2016) Tough polypseudorotaxane supramolecular hydrogels with dual-responsive shape memory properties. J Mater Chem B 4:1924–1931

    Article  CAS  Google Scholar 

  84. Wang J, Liu F, Tao F, Pan Q (2017) Rationally designed self-healing hydrogel electrolyte toward a smart and sustainable supercapacitor. ACS Appl Mater Interfaces 9:27745–27753

    Article  CAS  Google Scholar 

  85. Shao C, Chang H, Wang M et al (2017) High-strength, tough, and self-healing nanocomposite physical hydrogels based on the synergistic effects of dynamic hydrogen bond and dual coordination bonds. ACS Appl Mater Interfaces 9:28305–28318

    Article  CAS  Google Scholar 

  86. Sabzi M, Samadi N, Abbasi F et al (2017) Bioinspired fully physically cross-linked double network hydrogels with a robust, tough and self-healing structure. Mater Sci Eng C 74:374–381

    Article  CAS  Google Scholar 

  87. Li X, Zhao Y, Li D et al (2017) Hybrid dual crosslinked polyacrylic acid hydrogels with ultrahigh mechanical strength, toughness and self-healing properties via soaking salt solution. Polymer 121:55–63

    Article  CAS  Google Scholar 

  88. Bian H, Wei L, Lin C et al (2018) Lignin-containing cellulose nanofibril-reinforced polyvinyl alcohol hydrogels. ACS Sustain Chem Eng 6:4821–4828

    Article  CAS  Google Scholar 

  89. Hua L, Lei T, Qian H et al (2021) 3D-printed porous tantalum: recent application in various drug delivery systems to repair hard tissue defects. Expert Opin Drug Deliv 18:625–634

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biomaterials, Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran

    Mehrnoosh Hasan Shahriari & Afra Hadjizadeh

  2. Department of Chemistry, Amirkabir University of Technology, Tehran, Iran

    Majid Abdouss

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  1. Mehrnoosh Hasan Shahriari
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  2. Afra Hadjizadeh
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Shahriari, M.H., Hadjizadeh, A. & Abdouss, M. Advances in self-healing hydrogels to repair tissue defects. Polym. Bull. 80, 1155–1177 (2023). https://doi.org/10.1007/s00289-022-04133-1

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