AccScience Publishing / IJB / Volume 10 / Issue 3 / DOI: 10.36922/ijb.3223
REVIEW

Exploring the potential of supramolecular hydrogels as advanced bioinks for bioprinting and biomedical applications

Gopinathan Janarthanan1 Shyam Kokkattunivarthil Uthaman2 Karthik Murugesh2 Sanjairaj Vijayavenkataraman1,3*
Show Less
1 The Vijay Lab, Division of Engineering, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
2 Research and Development Department, EcoWorld Pharm Co. Ltd, Damyang-gun, Jeollanam-do, South Korea
3 Department of Mechanical & Aerospace Engineering, Tandon School of Engineering, New York University, Brooklyn, New York, United States of America
IJB 2024, 10(3), 3223 https://doi.org/10.36922/ijb.3223
Submitted: 20 March 2024 | Accepted: 2 May 2024 | Published: 11 June 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Supramolecular hydrogels have emerged as versatile bioinks in tissue engineering, providing a promising avenue for constructing intricate and functional biological structures. This paper explores the significance of employing supramolecular hydrogels as advanced bioinks for three-dimensional bioprinting and various biomedical applications. Supramolecular hydrogels possess distinct and tunable characteristics attributed to the dynamic nature of supramolecular host–guest interactions alongside interactions based on DNA and peptides, which increases their significance in tissue engineering. These interactions are essential for enhancing the mechanical properties, injectability, printability, post-printing stability, and biocompatibility of hydrogels. Gelation kinetics and rheological properties can also be manipulated to suit specific printing techniques. Furthermore, these supramolecular interactions facilitate the incorporation of bioactive molecules to regulate cellular behavior and tissue development. These diverse interactions observed in supramolecular hydrogels underscore their ability to emulate the dynamic and responsive nature of the cell’s extracellular matrix, which fosters cell growth, adherence, and differentiation. This review specifically highlights the cucurbit[n]uril and cyclodextrin-based host–guest supramolecular hydrogels, as well as peptide and DNA-based supramolecular structures as advanced bioinks and brief examples of their applications in various biomedical fields. These advanced bioinks would drive the development of intricate tissue constructs with enhanced biomimicry and therapeutic potential in regenerative medicine.

Keywords
Supramolecular hydrogels
Advanced bioinks
Host–guest
3D bioprinting
DNA bioinks
Peptide bioinks
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. S.V. was supported by the start-up funds from the New York University, Abu Dhabi.
Conflict of interest
The authors declare no conflicts of interest.
References
  1. Xiang T, Guo Q, Jia L, et al. Multifunctional hydrogels for the healing of diabetic wounds. Adv Healthc Mater. 2023:2301885. doi: 10.1002/adhm.202301885
  2. Gelmi A, Schutt CE. Stimuli‐responsive biomaterials: scaffolds for stem cell control. Adv Healthc Mater. 2021;10(1):2001125. doi: 10.1002/adhm.202001125
  3. Lim J, Lin Q, Xue K, Loh X. Recent advances in supramolecular hydrogels for biomedical applications. Mater Today Adv. 2019;3:100021. doi: 10.1016/j.mtadv.2019.100021
  4. Karoyo AH, Wilson LD. Physicochemical properties and the gelation process of supramolecular hydrogels: a review. Gels. 2017;3(1):1. doi: 10.3390/gels3010001
  5. Skopinska-Wisniewska J, De la Flor S, Kozlowska J. From supramolecular hydrogels to multifunctional carriers for biologically active substances. Int J Mol Sci. 2021;22(14):7402. doi: 10.3390/ijms22147402
  6. Saunders L, Ma PX. Self‐healing supramolecular hydrogels for tissue engineering applications. Macromol Biosci. 2019;19(1):1800313. doi: 10.1002/mabi.201800313
  7. Dong R, Zhou Y, Huang X, Zhu X, Lu Y, Shen J. Functional supramolecular polymers for biomedical applications. Adv Mater. 2015;27(3):498-526. doi: 10.1002/adma.201402975
  8. Dong R, Pang Y, Su Y, Zhu X. Supramolecular hydrogels: synthesis, properties and their biomedical applications. Biomater Sci. 2015;3(7):937-954. doi: 10.1039/C4BM00448E
  9. Malík M, Velechovský J, Tlustoš P. Natural pentacyclic triterpenoid acids potentially useful as biocompatible nanocarriers. Fitoterapia. 2021;151:104845. doi: 10.1016/j.fitote.2021.104845
  10. Xu C, Yu B, Qi Y, Zhao N, Xu FJ. Versatile types of cyclodextrin‐based nucleic acid delivery systems. Adv Healthc Mater. 2021;10(1):2001183. doi: 10.1002/adhm.202001183
  11. Cai Y, Zheng C, Xiong F, et al. Recent progress in the design and application of supramolecular peptide hydrogels in cancer therapy. Adv Healthc Mater. 2021;10(1):2001239. doi: 10.1002/adhm.202001239
  12. Ayoubi‐Joshaghani MH, Seidi K, Azizi M, et al. Potential applications of advanced nano/hydrogels in biomedicine: static, dynamic, multi‐stage, and bioinspired. Adv Funct Mater. 2020;30(45):2004098. doi: 10.1002/adfm.202004098
  13. Hu J-H, Huang Y, Redshaw C, Tao Z, Xiao X. Cucurbit [n] uril-based supramolecular hydrogels: synthesis, properties and applications. Coord Chem Rev. 2023;489:215194. doi: 10.1016/j.ccr.2023.215194
  14. Raymond DM, Abraham BL, Fujita T, et al. Low-molecular-weight supramolecular hydrogels for sustained and localized in vivo drug delivery. ACS Appl Bio Mater. 2019;2(5): 2116-2124. doi: 10.1021/acsabm.9b00125
  15. Hao Z, Li H, Wang Y, et al. Supramolecular peptide nanofiber hydrogels for bone tissue engineering: from multihierarchical fabrications to comprehensive applications. Adv Sci. 2022;9(11):2103820. doi: 10.1002/advs.202103820
  16. Dong RJ, Pang Y, Su Y, Zhu XY. Supramolecular hydrogels: synthesis, properties and their biomedical applications. Biomater Sci. 2015;3(7):937-954. doi: 10.1039/c4bm00448e
  17. Wang X, Wang J, Yang YY, Yang F, Wu DC. Fabrication of multi-stimuli responsive supramolecular hydrogels based on host-guest inclusion complexation of a tadpole-shaped cyclodextrin derivative with the azobenzene dimer. Polym Chem-Uk. 2017;8(26):3901-3909. doi: 10.1039/c7py00698e
  18. Chen Y, Pang XH, Dong CM. Dual stimuli-responsive supramolecular polypeptide-based hydrogel and reverse micellar hydrogel mediated by host-guest chemistry. Adv Funct Mater. 2010;20(4):579-586. doi: 10.1002/adfm.200901400
  19. Ghosh G, Barman R, Sarkar J, Ghosh S. pH-responsive biocompatible supramolecular peptide hydrogel. J Phys Chem B. 2019;123(27):5909-5915. doi: 10.1021/acs.jpcb.9b02999
  20. Wang Q, Zhang YY, Dai XY, Shi XH, Liu WG. A high strength pH responsive supramolecular copolymer hydrogel. Sci China Technol Sc. 2017;60(1):78-83. doi: 10.1007/s11431-016-0698-0
  21. Zhu CN, Zheng SY, Qiu HN, et al. Plastic-like supramolecular hydrogels with polyelectrolyte/surfactant complexes as physical crosslinks. Macromolecules. 2021;54(17): 8052-8066. doi: 10.1021/acs.macromol.1c00835
  22. Bernhard S, Tibbitt MW. Supramolecular engineering of hydrogels for drug delivery. Adv Drug Deliv Rev. 2021;171:240-256. doi: 10.1016/j.addr.2021.02.002
  23. Raina N, Pahwa R, Bhattacharya J, et al. Drug delivery strategies and biomedical significance of hydrogels: translational considerations. Pharmaceutics. 2022;14(3):574. doi: 10.1002/btm2.10147
  24. O’Connor JP, Kanjilal D, Teitelbaum M, Lin SS, Cottrell JA. Zinc as a therapeutic agent in bone regeneration. Materials. 2020;13(10). doi: 10.3390/ma13102211
  25. Chandramohan Y, Jeganathan K, Sivanesan S, et al. Assessment of human ovarian follicular fluid derived mesenchymal stem cells in chitosan/PCL/Zn scaffold for bone tissue regeneration. Life Sci. 2021;264. doi: 10.1016/j.lfs.2020.118502
  26. Wahid F, Zhou Y-N, Wang H-S, Wan T, Zhong C, Chu L-Q. Injectable self-healing carboxymethyl chitosan-zinc supramolecular hydrogels and their antibacterial activity. Int J Biol Macromol. 2018;114:1233-1239. doi: 10.1002/adhm.201900847
  27. Xu J, Feng Q, Lin S, et al. Injectable stem cell-laden supramolecular hydrogels enhance in situ osteochondral regeneration via the sustained co-delivery of hydrophilic and hydrophobic chondrogenic molecules. Biomaterials. 2019;210:51-61. doi: 10.1016/j.biomaterials.2019.04.031
  28. Grosskopf AK, Roth GA, Smith AA, Gale EC, Hernandez HL, Appel EA. Injectable supramolecular polymer– nanoparticle hydrogels enhance human mesenchymal stem cell delivery. Bioeng Transl Med. 2020;5(1):e10147. doi: 10.1186/s40824-018-0122-1
  29. Aguado BA, Mulyasasmita W, Su J, Lampe KJ, Heilshorn SC. Improving viability of stem cells during syringe needle flow through the design of hydrogel cell carriers. Tissue Eng Part A. 2012;18(7-8):806-815. doi: 10.1021/acs.chemrev.0c00015
  30. Lopez Hernandez H, Grosskopf AK, Stapleton LM, Agmon G, Appel EA. Non‐Newtonian polymer–nanoparticle hydrogels enhance cell viability during injection. Macromol Biosci. 2019;19(1):1800275. doi: 10.1016/j.polymer.2018.08.029
  31. Mol EA, Lei Z, Roefs MT, et al. Injectable supramolecular ureidopyrimidinone hydrogels provide sustained release of extracellular vesicle therapeutics. Adv Healthc Mater. 2019;8(20):1900847. doi: 10.1002/anie.201804400
  32. Meis CM, Grosskopf AK, Correa S, Appel EA. Injectable supramolecular polymer-nanoparticle hydrogels for cell and drug delivery applications. J Vis Exp: JoVE. 2021;(168). doi: 10.1002/anie.201804400
  33. Zhao Y, Song S, Ren X, Zhang J, Lin Q, Zhao Y. Supramolecular adhesive hydrogels for tissue engineering applications. Chem Rev. 2022;122(6):5604-5640. doi: 10.1021/acs.chemrev.1c00815
  34. Morwood AJ, El-Karim IA, Clarke SA, Lundy FT. The role of extracellular matrix (ECM) adhesion motifs in functionalised hydrogels. Molecules. 2023;28(12):4616. doi: 10.3390/molecules28124616
  35. Zhang ZP, Hu J, Ma PX. Nanofiber-based delivery of bioactive agents and stem cells to bone sites. Adv Drug Deliv Rev. 2012;64(12):1129-1141. doi: 10.1016/j.addr.2012.04.008
  36. Luo ZL, Zhang SG. Designer nanomaterials using chiral self-assembling peptide systems and their emerging benefit for society. Chem Soc Rev. 2012;41(13):4736-4754. doi: 10.1039/c2cs15360b
  37. Yang YL, Khoe U, Wang XM, Horii A, Yokoi H, Zhang SG. Designer self-assembling peptide nanomaterials. Nano Today. 2009;4(2):193-210. doi: 10.1016/j.nantod.2009.02.009
  38. Shi L, Ding P, Wang Y, Zhang Y, Ossipov D, Hilborn J. Self‐healing polymeric hydrogel formed by metal–ligand coordination assembly: design, fabrication, and biomedical applications. Macromol Rapid Commun. 2019;40(7):1800837. doi: 10.1002/marc.201800837
  39. Gopinathan J, Noh I. Recent trends in bioinks for 3D printing. Biomater Res. 2018;22(1):11. doi: 10.1186/s40824-018-0122-1
  40. Lee SC, Gillispie G, Prim P, Lee SJ. Physical and chemical factors influencing the printability of hydrogel-based extrusion bioinks. Chem Rev. 2020;120(19):10834-10886. doi: 10.1021/acs.chemrev.0c00015
  41. Li H, Wang H, Zhang D, Xu Z, Liu W. A highly tough and stiff supramolecular polymer double network hydrogel. Polymer. 2018;153:193-200. doi: 10.1016/j.polymer.2018.08.029
  42. Wang Z, Ren Y, Zhu Y, et al. A rapidly self‐healing host– guest supramolecular hydrogel with high mechanical strength and excellent biocompatibility. Angew Chem Int Ed. 2018;57(29):9008-9012. doi: 10.1002/anie.201804400
  43. Wu Q, Wei J, Xu B, et al. A robust, highly stretchable supramolecular polymer conductive hydrogel with self-healability and thermo-processability. Sci Rep. 2017;7(1):1-11. doi: 10.1002/anie.201804400
  44. Zhu S, Wang J, Yan H, et al. An injectable supramolecular self-healing bio-hydrogel with high stretchability, extensibility and ductility, and a high swelling ratio. J Mater Chem B. 2017;5(34):7021-7034. doi: 10.1039/C7TB01183K
  45. Lorson T, Jaksch S, Lübtow MM, et al. A thermogelling supramolecular hydrogel with sponge-like morphology as a cytocompatible bioink. Biomacromolecules. 2017;18(7): 2161-2171. doi: 10.1021/acs.biomac.7b00481
  46. Li L, Tian X, Yu X, Dong S. Effects of acute and chronic heavy metal (Cu, Cd, and Zn) exposure on sea cucumbers (Apostichopus japonicus). Biomed Res Int. 2016;2016:4532697. doi: 10.1155/2016/4532697
  47. Hu T, Cui X, Zhu M, et al. 3D-printable supramolecular hydrogels with shear-thinning property: fabricating strength tunable bioink via dual crosslinking. Bioact Mater. 2020;5(4):808-818. doi: 10.1016/j.bioactmat.2020.06.001
  48. Gao F, Xu Z, Liang Q, et al. Osteochondral regeneration with 3D‐printed biodegradable high‐strength supramolecular polymer reinforced‐gelatin hydrogel scaffolds. Adv Sci. 2019;6(15):1900867. doi: 10.1002/advs.201900867
  49. Godoy-Gallardo M, Merino-Gómez M, Mateos-Timoneda MA, Eckhard U, Gil FJ, Perez RA. Advanced binary guanosine and guanosine 5’-monophosphate cell-laden hydrogels for soft tissue reconstruction by 3D bioprinting. ACS Appl Mater Interfaces. 2023;15(25):29729-29742. doi: 10.1021/acsami.2c23277
  50. Yang J, Fatima K, Zhou X, He C. Meticulously engineered three-dimensional-printed scaffold with microarchitecture and controlled peptide release for enhanced bone regeneration. Biomater Trans. 2024;5(1):69. doi: 10.12336/biomatertransl.2024.01.007
  51. Li X, Jian H, Han Q, et al. Three-dimensional (3D) bioprinting of medium toughened dipeptide hydrogel scaffolds with Hofmeister effect. J Colloid Interface Sci. 2023;639:1-6. doi: 10.1016/j.jcis.2023.02.033
  52. Liu X, Song S, Chen Z, et al. Release of O-GlcNAc transferase inhibitor promotes neuronal differentiation of neural stem cells in 3D bioprinted supramolecular hydrogel scaffold for spinal cord injury repair. Acta Biomater. 2022;151:148-162. doi: 10.1016/j.actbio.2022.08.031
  53. Shim J-H, Jang K-M, Hahn SK, et al. Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint. Biofabrication. 2016;8(1):014102. doi: 10.1088/1758-5090/8/1/014102
  54. Chen H, Hou S, Ma H, Li X, Tan Y. Controlled gelation kinetics of cucurbit[7]uril-adamantane crosslinked supramolecular hydrogels with competing guest molecules. Sci Rep. 2016;6(1):20722. doi: 10.1038/srep20722
  55. Gao W, Chao H, Zheng Y-C, et al. Ionic carbazole-based water-soluble two-photon photoinitiator and the fabrication of biocompatible 3D hydrogel scaffold. ACS Appl Mater Interf. 2021;13(24):27796-27805. doi: 10.1021/acsami.1c02227
  56. Madl AC, Madl CM, Myung D. Injectable cucurbit [8] uril-based supramolecular gelatin hydrogels for cell encapsulation. ACS Macro Lett. 2020;9(4):619-626. doi: 10.1021/acsmacrolett.0c00184
  57. Zou H, Liu J, Li Y, Li X, Wang X. Cucurbit [8] uril‐based polymers and polymer materials. Small. 2018;14(46):1802234. doi: 10.1002/smll.201802234
  58. Liu YH, Zhang YM, Yu HJ, Liu Y. Cucurbituril‐based biomacromolecular assemblies. Angew Chem. 2021;133(8):3914-3924. doi: 10.1002/anie.202009797
  59. Wang Z, Shui M, Wyman IW, Zhang Q-W, Wang R. Cucurbit [8] uril-based supramolecular hydrogels for biomedical applications. RSC Med Chem. 2021;12(5):722-729. doi: 10.3390/molecules28083566
  60. Meng Z-J, Liu J, Yu Z, et al. Viscoelastic hydrogel microfibers exploiting cucurbit [8] uril host–guest chemistry and microfluidics. ACS Appl Mater Interfaces. 2020;12(15): 17929-17935. doi: 10.1021/acsami.9b21240
  61. Zou L, Braegelman AS, Webber MJ. Dynamic supramolecular hydrogels spanning an unprecedented range of host–guest affinity. ACS Appl Mater Interfaces. 2019;11(6):5695-5700. doi: 10.1021/acsami.8b22151
  62. Madl AC, Myung D. Supramolecular host–guest hydrogels for corneal regeneration. Gels. 2021;7(4):163. doi: 10.3390/gels7040163
  63. Wang Y, Zhang X, Wan K, Zhou N, Wei G, Su Z. Supramolecular peptide nano-assemblies for cancer diagnosis and therapy: from molecular design to material synthesis and function-specific applications. J Nanobiotechnol. 2021;19(1):1-31. doi: 10.1186/s12951-021-00999-x
  64. Wang H, Zhu H, Fu W, et al. A high strength self‐healable antibacterial and anti‐inflammatory supramolecular polymer hydrogel. Macromol Rapid Commun. 2017;38(9):1600695. doi: 10.1002/marc.201600695
  65. Park KM, Roh JH, Sung G, Murray J, Kim K. Self‐healable supramolecular hydrogel formed by nor‐seco‐cucurbit [10] uril as a supramolecular crosslinker. Chem Asian J. 2017;12(13):1461-1464. doi: 10.1002/asia.201700386
  66. Xiao T, Xu L, Zhou L, Sun X-Q, Lin C, Wang L. Dynamic hydrogels mediated by macrocyclic host–guest interactions. J Mater Chem B. 2019;7(10):1526-1540. doi: 10.1039/C8TB02339E
  67. Zhou Y, Zhang Y, Dai Z, Jiang F, Tian J, Zhang W. A super-stretchable, self-healing and injectable supramolecular hydrogel constructed by a host–guest crosslinker. Biomater Sci. 2020;8(12):3359-3369. doi: 10.1039/D0BM00290A
  68. Miller B, Hansrisuk A, Highley CB, Caliari SR. Guest–host supramolecular assembly of injectable hydrogel nanofibers for cell encapsulation. ACS Biomater Sci Eng. 2021;7(9): 4164-4174. doi: 10.1021/acsbiomaterials.1c00275
  69. Dai W, Zhang L, Yu Y, et al. 3D bioprinting of heterogeneous constructs providing tissue-specific microenvironment based on host–guest modulated dynamic hydrogel bioink for osteochondral regeneration. Adv Funct Mater. 2022;32(23):2200710. doi: 10.1002/adfm.202200710
  70. Wei W, Liu W, Kang H, et al. A one-stone-two-birds strategy for osteochondral regeneration based on a 3D printable biomimetic scaffold with kartogenin biochemical stimuli gradient. Adv Healthc Mater. 2023;12(15):2300108. doi: 10.1002/adhm.202300108
  71. Jain M, Nowak BP, Ravoo BJ. Supramolecular hydrogels based on cyclodextrins: progress and perspectives. Chem Nano Mat. 2022;8(5):e202200077. doi: 10.1002/cnma.202200077
  72. Rey-Rico A, Babicz H, Madry H, Concheiro A, Alvarez-Lorenzo C, Cucchiarini M. Supramolecular polypseudorotaxane gels for controlled delivery of rAAV vectors in human mesenchymal stem cells for regenerative medicine. Int J Pharm. 2017;531(2):492-503. doi: 10.1016/j.ijpharm.2017.05.050
  73. Alvarez-Lorenzo C, Garcia-Gonzalez CA, Concheiro A. Cyclodextrins as versatile building blocks for regenerative medicine. JCR. 2017;268:269-281. doi: 10.1016/j.jconrel.2017.10.038
  74. Xia D, Wang P, Ji X, Khashab NM, Sessler JL, Huang F. Functional supramolecular polymeric networks: the marriage of covalent polymers and macrocycle-based host– guest interactions. Chem Rev. 2020;120(13):6070-6123. doi: 10.1021/acs.chemrev.9b00839
  75. Harada A, Okada M, Li J, Kamachi M. Preparation and characterization of inclusion complexes of poly (propylene glycol) with cyclodextrins. Macromolecules. 1995;28(24):8406-8411. doi: 10.1021/ma00128a060
  76. Simões S, Veiga F, Torres-Labandeira J, et al. Syringeable pluronic–α-cyclodextrin supramolecular gels for sustained delivery of vancomycin. Eur J Pharm Biopharm. 2012;80(1):103-112. doi: 10.1016/j.ejpb.2011.09.017
  77. Li J, Li X, Ni X, Wang X, Li H, Leong KW. Self-assembled supramolecular hydrogels formed by biodegradable PEO–PHB–PEO triblock copolymers and α-cyclodextrin for controlled drug delivery. Biomaterials. 2006;27(22): 4132-4140. doi: 10.1016/j.biomaterials.2006.03.025
  78. Khodaverdi E, Heidari Z, Tabassi SAS, et al. Injectable supramolecular hydrogel from insulin-loaded triblock PCL-PEG-PCL copolymer and γ-cyclodextrin with sustained-release property. AAPS Pharm Sci Tech. 2015;16:140-149. doi: 10.1208/s12249-014-0198-4
  79. Rey-Rico A, Cucchiarini M. Supramolecular cyclodextrin-based hydrogels for controlled gene delivery. Polymers. 2019;11(3):514. doi: 10.3390/polym11030514
  80. Kauscher U, Stuart MCA, Drücker P, Galla H-J, Ravoo BJ.Incorporation of amphiphilic cyclodextrins into liposomes as artificial receptor units. Langmuir. 2013;29(24): 7377-7383. doi: 10.1021/la3045434
  81. Redondo-Gómez C, Abdouni Y, Becer CR, Mata A. Self-assembling hydrogels based on a complementary host–guest peptide amphiphile pair. Biomacromolecules. 2019;20(6):2276-2285. doi: 10.1021/acsbiomaterials.0c00549
  82. Redondo-Gómez C, Padilla-Lopategui S, Azevedo HS, Mata A. Host–guest-mediated epitope presentation on self-assembled peptide amphiphile hydrogels. ACS Biomater Sci Eng. 2020;6(9):4870-4880. doi: 10.1021/acsbiomaterials.0c00549
  83. Nowak BP, Ravoo BJ. Magneto-and photo-responsive hydrogels from the co-assembly of peptides, cyclodextrins, and superparamagnetic nanoparticles. Farad Disc. 2019;219:220-228. doi: 10.1039/C9FD00012G
  84. Wang J, Williamson GS, Yang H. Branched polyrotaxane hydrogels consisting of alpha-cyclodextrin and low-molecular-weight four-arm polyethylene glycol and the utility of their thixotropic property for controlled drug release. Colloids Surf B Biointerfaces. 2018;165:144-149. doi: 10.1016/j.colsurfb.2018.02.032
  85. Dai L, Liu K, Wang L, et al. Injectable and thermosensitive supramolecular hydrogels by inclusion complexation between binary-drug loaded micelles and α-cyclodextrin. Mater Sci Eng C. 2017;76:966-974. doi: 10.1002/adfm.202200710
  86. Zohreband Z, Adeli M, Zebardasti A. Self-healable and flexible supramolecular gelatin/MoS2 hydrogels with molecular recognition properties. Int J Biol Macromol. 2021;182:2048-2055. doi: 10.1016/j.ijbiomac.2021.05.106
  87. Singh A, Zhan J, Ye Z, Elisseeff JH. Modular multifunctional poly (ethylene glycol) hydrogels for stem cell differentiation. Adv Funct Mater. 2013;23(5):575-582. doi: 10.1002/adfm.201201902
  88. Aramoto H, Osaki M, Konishi S, et al. Redox-responsive supramolecular polymeric networks having double-threaded inclusion complexes. Chem Sci. 2020;11(17): 4322-4331. doi: 10.1039/C9SC05589D
  89. Arisaka Y, Tonegawa A, Tamura A, Yui N. Terminally cross‐linking polyrotaxane hydrogels applicable for cellular microenvironments. J Appl Polym Sci. 2021;138(3):49706. doi: 10.1002/app.49706
  90. Arisaka Y, Yui N. Polyrotaxane-based biointerfaces with dynamic biomaterial functions. J Mater Chem B. 2019;7(13):2123-2129. doi: 10.1039/C9TB00256A
  91. Cho IS, Ooya T. Cell‐encapsulating hydrogel puzzle: polyrotaxane‐based self‐healing hydrogels. Chem A Eur J. 2020;26(4):913-920. doi: 10.1002/chem.201904446
  92. Uekama K, Hirayama F, Irie T. Cyclodextrin drug carrier systems. Chem Rev. 1998;98(5):2045-2076. doi: 10.1021/cr970025p
  93. Li Z, Yin H, Zhang Z, Liu KL, Li J. Supramolecular anchoring of DNA polyplexes in cyclodextrin-based polypseudorotaxane hydrogels for sustained gene delivery. Biomacromolecules. 2012;13(10):3162-3172. doi: 10.1021/bm300936x
  94. Segredo-Morales E, Martin-Pastor M, Salas A, et al. Mobility of water and polymer species and rheological properties of supramolecular polypseudorotaxane gels suitable for bone regeneration. Bioconjug Chem. 2018;29(2):503-516. doi: 10.1021/acs.bioconjchem.7b00823
  95. Ohshita N, Motoyama K, Iohara D, et al. Polypseudorotaxane-based supramolecular hydrogels consisting of cyclodextrins and Pluronics as stabilizing agents for antibody drugs. Carbohydr Polym. 2021;256:117419. doi: 10.1016/j.carbpol.2020.117419
  96. Jian H, Wang M, Dong Q, et al. Dipeptide self-assembled hydrogels with tunable mechanical properties and degradability for 3D bioprinting. ACS Appl Materi Inter. 2019;11(50):46419-46426. doi: 10.1021/acsami.9b13905
  97. Farsheed AC, Thomas AJ, Pogostin BH, Hartgerink JD. 3D printing of self‐assembling nanofibrous multidomain peptide hydrogels. Adv Materi. 2023;35(11):2210378. doi: 10.1002/adma.202210378
  98. Chu B, He J-m, Wang Z, et al. Proangiogenic peptide nanofiber hydrogel/3D printed scaffold for dermal regeneration. Chem Eng J. 2021;424:128146. doi: 10.1016/j.cej.2020.128146
  99. Li Y, Wang F, Cui H. Peptide‐based supramolecular hydrogels for delivery of biologics. Bioeng Transl Med. 2016;1(3): 306-322. doi: 10.1002/btm2.10041
  100. Jagrosse ML, Agredo P, Abraham BL, Toriki ES, Nilsson BL. Supramolecular phenylalanine-derived hydrogels for the sustained release of functional proteins. ACS Biomater Sci Eng. 2023;9(2):784-796. doi: 10.1021/acsbiomaterials.2c01299
  101. Rajbhandary A, Raymond DM, Nilsson BL. Self-assembly, hydrogelation, and nanotube formation by cation-modified phenylalanine derivatives. Langmuir. 2017;33(23): 5803-5813. doi: 10.1021/acs.langmuir.7b00686
  102. Misra R, Tang Y, Chen Y, et al. Exploiting minimalistic backbone engineered γ‐phenylalanine for the formation of supramolecular co‐polymer. Macromol Rapid Commun. 2022;43(19):2200223. doi: 10.1002/marc.202200223
  103. Li W, Hu X, Chen J, Wei Z, Song C, Huang R. N-(9- Fluorenylmethoxycarbonyl)-L-phenylalanine/nano-hydroxyapatite hybrid supramolecular hydrogels as drug delivery vehicles with antibacterial property and cytocompatibility. J Mater Sci: Mater Med. 2020;31:1-9. doi: 10.1007/s10856-020-06410-9
  104. Dang-i AY, Kousar A, Liu J, et al. Mechanically stable C2-phenylalanine hybrid hydrogels for manipulating cell adhesion. ACS Appl Mater Interfaces. 2019;11(32): 28657-28664. doi: 10.1021/acsami.9b08655
  105. Chakraborty P, Ghosh M, Schnaider L, et al. Composite of peptide‐supramolecular polymer and covalent polymer comprises a new multifunctional, bio‐inspired soft material. Macromol Rapid Commun. 2019;40(18):1900175. doi: 10.1002/marc.201900175
  106. Misra R, Sharma A, Shiras A, Gopi HN. Backbone engineered γ-peptide amphitropic gels for immobilization of semiconductor quantum dots and 2D cell culture. Langmuir. 2017;33(31):7762-7768. doi: 10.1021/acs.langmuir.7b01283
  107. Wu C, Li R, Yin Y, Wang J, Zhang L, Zhong W. Redox-responsive supramolecular hydrogel based on 10-hydroxy camptothecin-peptide covalent conjugates with high loading capacity for drug delivery. Mater Sci Eng C. 2017;76: 196-202. doi: 10.1016/j.msec.2017.03.103
  108. Ren C, Gao Y, Liu J, et al. Anticancer supramolecular hydrogel of D/L-peptide with enhanced stability and bioactivity. J Biomed Nanotechnol. 2018;14(6):1125-1134. doi: 10.1166/jbn.2018.2564
  109. Wei K, Chen X, Zhao P, et al. Stretchable and bioadhesive supramolecular hydrogels activated by a one-stone–two-bird postgelation functionalization method. ACS Appl Mater Interfaces. 2019;11(18):16328-16335. doi: 10.1021/acsami.9b03029
  110. Zhang Y, Zhang H, Zou Q, Xing R, Jiao T, Yan X. An injectable dipeptide–fullerene supramolecular hydrogel for photodynamic antibacterial therapy. J Mater Chem B. 2018;6(44):7335-7342. doi: 10.1039/C8TB01487F
  111. Clarke DE, Parmenter CD, Scherman OA. Tunable pentapeptide self‐assembled β‐sheet hydrogels. Angew Chem Int Ed. 2018;57(26):7709-7713. doi: 10.1002/anie.201801001
  112. Diaferia C, Netti F, Ghosh M, et al. Bi-functional peptide-based 3D hydrogel-scaffolds. Soft Matter. 2020;16(30): 7006-7017. doi: 10.1039/D0SM00825G
  113. Dorishetty P, Dutta NK, Choudhury NR. Bioprintable tough hydrogels for tissue engineering applications. Adv Colloid Interface Sci. 2020;281:102163. doi: 10.1016/j.cis.2020.102163
  114. Chakraborty P, Oved H, Bychenko D, et al. Nanoengineered peptide‐based antimicrobial conductive supramolecular biomaterial for cardiac tissue engineering. Adv Mater. 2021;33(26):2008715. doi: 10.1002/adma.202008715
  115. Falcone N, Shao T, Andoy NMO, et al. Multi-component peptide hydrogels–a systematic study incorporating biomolecules for the exploration of diverse, tuneable biomaterials. Biomater Sci. 2020;8(20):5601-5614. doi: 10.1039/D0BM01104E
  116. Fichman G, Schneider JP. Utilizing Frémy’s salt to increase the mechanical rigidity of supramolecular peptide-based gel networks. Fbioe. 2021;8:594258. doi: 10.3389/fbioe.2020.594258
  117. Chowdhuri S, Saha A, Pramanik B, et al. Smart thixotropic hydrogels by disulfide-linked short peptides for effective three-dimensional cell proliferation. Langmuir. 2020;36(50):15450-15462. doi: 10.1021/acs.langmuir.0c03324
  118. Mañas-Torres MC, Gila-Vilchez C, Vazquez-Perez FJ, et al. Injectable magnetic-responsive short-peptide supramolecular hydrogels: ex vivo and in vivo evaluation. ACS Appl Mater Interfaces. 2021;13(42):49692-49704. doi: 10.1021/acsami.1c13972
  119. Vrehen AF, Rutten MGTA, Dankers PYW. Development of a fully synthetic corneal stromal construct via supramolecular hydrogel engineering. Adv Healthc Mater. 2023;12(32):2301392. doi: 10.1002/adhm.202301392
  120. Zhou K, Ding R, Tao X, et al. Peptide-dendrimer-reinforced bioinks for 3D bioprinting of heterogeneous and biomimetic in vitro models. Acta Biomater. 2023;169:243-255. doi: 10.1016/j.actbio.2023.08.008
  121. Chiesa I, Ligorio C, Bonatti AF, et al. Modeling the three-dimensional bioprinting process of β-sheet self-assembling peptide hydrogel scaffolds. Fmedt. 2020;2:571626. doi: 10.3389/fmedt.2020.571626
  122. Aronsson C, Jury M, Naeimipour S, et al. Dynamic peptide-folding mediated biofunctionalization and modulation of hydrogels for 4D bioprinting. Biofabrication. 2020;12(3):035031. doi: 10.1088/1758-5090/ab9490
  123. Zhao Y, Xing Y, Wang M, et al. Supramolecular hydrogel based on an osteogenic growth peptide promotes bone defect repair. ACS Omega. 2022;7(13):11395-11404. doi: 10.1021/acsomega.2c00501
  124. Yan M, Lewis P, Shah R. Tailoring nanostructure and bioactivity of 3D-printable hydrogels with self-assemble peptides amphiphile (PA) for promoting bile duct formation. Biofabrication. 2018;10(3):035010. doi: 10.1088/1758-5090/aac902
  125. Sather NA, Sai H, Sasselli IR, et al. 3D printing of supramolecular polymer hydrogels with hierarchical structure. Small. 2021;17(5):2005743. doi: 10.1002/smll.202005743
  126. Das AK, Gavel PK. Low molecular weight self-assembling peptide-based materials for cell culture, antimicrobial, anti-inflammatory, wound healing, anticancer, drug delivery, bioimaging and 3D bioprinting applications. Soft Matter. 2020;16(44):10065-10095. doi: 10.1039/D0SM01136C
  127. Cai L, Liu S, Guo J, Jia Y-G. Polypeptide-based self-healing hydrogels: design and biomedical applications. Acta Biomater. 2020;113:84-100. doi: 10.1016/j.actbio.2020.07.001
  128. Li C, Faulkner‐Jones A, Dun AR, et al. Rapid formation of a supramolecular polypeptide–DNA hydrogel for in situ three‐dimensional multilayer bioprinting. Angew Chem Int Ed. 2015;54(13):3957-3961. doi: 10.1002/anie.201411383
  129. Zhang J, Lu N, Peng H, et al. Multi-triggered and enzyme-mimicking graphene oxide/polyvinyl alcohol/G-quartet supramolecular hydrogels. Nanoscale. 2020;12(8): 5186-5195. doi: 10.1039/C9NR10779G
  130. Yang B, Zhao Z, Pan Y, et al. Shear-thinning and designable responsive supramolecular DNA hydrogels based on chemically branched DNA. ACS Appl Mater Interfaces. 2021;13(41):48414-48422. doi: 10.1021/acsami.1c15494
  131. Wu J, Liyarita BR, Zhu H, Liu M, Hu X, Shao F. Self-assembly of dendritic DNA into a hydrogel: application in three-dimensional cell culture. ACS Appl Mater Interfaces. 2021;13(42):49705-49712. doi: 10.1021/acsami.1c14445
  132. Sousa V, Amaral AJ, Castanheira EJ, et al. Self-supporting hyaluronic acid-functionalized G-quadruplex-based perfusable multicomponent hydrogels embedded in photo-crosslinkable matrices for bioapplications. Biomacromolecules. 2023;24(7):3380-3396. doi: 10.1021/acs.biomac.3c00433
  133. Tang Q, Plank TN, Zhu T, et al. Self-assembly of metallo-nucleoside hydrogels for injectable materials that promote wound closure. ACS Appl Mater Interfaces. 2019;11(22):19743-19750. doi: 10.1021/acsami.9b02265
  134. Shen CY, Wang J, Li GF, et al. Boosting cartilage repair with silk fibroin-DNA hydrogel-based cartilage organoid precursor. Bioact Mater. May 2024;35:429-444. doi: 10.1016/j.bioactmat.2024.02.016
  135. Shi J, Shi Z, Dong Y, Wu F, Liu D. Responsive DNA-based supramolecular hydrogels. ACS Appl Bio Mater. 2020;3(5):2827-2837. doi: 10.1021/acsabm.0c00081
  136. Shao Y, Jia H, Cao T, Liu D. Supramolecular hydrogels based on DNA self-assembly. Acc Chem Res. 2017;50(4):659-668. doi: 10.1021/acs.accounts.6b00524
  137. Wei Y, Wang K, Luo S, et al. Programmable DNA hydrogels as artificial extracellular matrix. Small. 2022;18(36):2107640. doi: 10.1002/smll.202107640
  138. Budharaju H, Zennifer A, Sethuraman S, Paul A, Sundaramurthi D. Designer DNA biomolecules as a defined biomaterial for 3D bioprinting applications. Mater Horiz. 2022;9(4):1141-1166. doi: 10.1039/D1MH01632F
  139. Wang D, Duan J, Liu J, et al. Stimuli-responsive self-degradable DNA hydrogels: design, synthesis, and applications. Adv Healthc Mater. 2023;12(16):2203031. doi: 10.1002/adhm.202203031
  140. Tang M, Zhong Z, Ke C. Advanced supramolecular design for direct ink writing of soft materials. Chem Soc Rev. 2023;52(5):1614-1649. doi: 10.1039/D2CS01011A
  141. Miao Y, Chen Y, Luo J, et al. Black phosphorus nanosheets-enabled DNA hydrogel integrating 3D-printed scaffold for promoting vascularized bone regeneration. Bioact Mater. 2023;21:97-109. doi: 10.1016/j.bioactmat.2022.08.005
  142. Li J, Lai Y, Li M, et al. Repair of infected bone defect with clindamycin-tetrahedral DNA nanostructure complex-loaded 3D bioprinted hybrid scaffold. Chem Eng J. 2022;435:134855. doi: 10.1016/j.cej.2022.134855
  143. Wu W, Zhang Z, Xiong T, et al. Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic alternative for control of non-infectious uveitis. Acta Biomater. 2017;61:157-168. doi: 10.1016/j.actbio.2017.05.024
  144. Chen Z, Xing L, Fan Q, et al. Drug-bearing supramolecular filament hydrogels as anti-inflammatory agents. Theranostics. 2017;7(7):2003. doi: 10.7150/thno.19404
  145. Liu X, Chen X, Chua MX, Li Z, Loh XJ, Wu YL. Injectable supramolecular hydrogels as delivery agents of Bcl‐2 conversion gene for the effective shrinkage of therapeutic resistance tumors. Adv Healthc Mater. 2017;6(11):1700159. doi: 10.1002/adhm.201700159
  146. Liu Z, Xu G, Wang C, Li C, Yao P. Shear-responsive injectable supramolecular hydrogel releasing doxorubicin loaded micelles with pH-sensitivity for local tumor chemotherapy. Int J Pharm. 2017;530(1-2):53-62. doi: 10.1016/j.ijpharm.2017.07.063
  147. Bakker MH, van Rooij E, Dankers PY. Controlled release of RNAi molecules by tunable supramolecular hydrogel carriers. Chem Asian J. 2018;13(22):3501-3508. doi: 10.1002/asia.201800582
  148. Liu X, Chen X, Chua MX, Li Z, Loh XJ, Wu Y-L. Injectable supramolecular hydrogels as delivery agents of Bcl-2 conversion gene for the effective shrinkage of therapeutic resistance tumors. Adv Healthc Mater. 2017;6(11):1700159. doi: 10.1002/adhm.201700159
  149. d’Aquino AI, Maikawa CL, Nguyen LT, et al. Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management. Cell Rep Med. 2023;4(11): 101292. doi: 10.1016/j.xcrm.2023.101292
  150. Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov. 2004;3(12):1023-1035. doi: 10.1038/nrd1576
  151. Ma D, Zhang L-M. Novel biosensing platform based on self-assembled supramolecular hydrogel. Mater Sci Eng C. 2013;33(5):2632-2638. doi: 10.1016/j.msec.2013.02.023
  152. Li J, Kuang Y, Gao Y, Du X, Shi J, Xu B. D-amino acids boost the selectivity and confer supramolecular hydrogels of a nonsteroidal anti-inflammatory drug (NSAID). J Am Chem Soc. 2013;135(2):542-545. doi: 10.1021/ja310019x
  153. Li X, Li J, Gao Y, Kuang Y, Shi J, Xu B. Molecular nanofibers of olsalazine form supramolecular hydrogels for reductive release of an anti-inflammatory agent. J Am Chem Soc. 2010;132(50):17707-17709. doi: 10.1021/ja109269v
  154. Xuan X, Zhou Y, Chen A, et al. Silver crosslinked injectable bFGF-eluting supramolecular hydrogels speed up infected wound healing. J Mater Chem B. 2020;8(7): 1359-1370. doi: 10.1039/C9TB02331C
  155. Zhao W, Li Y, Zhang X, et al. Photo-responsive supramolecular hyaluronic acid hydrogels for accelerated wound healing. JCR. 2020;323:24-35. doi: 10.1016/j.jconrel.2020.04.014
  156. Niu Y, Guo T, Yuan X, Zhao Y, Ren L. An injectable supramolecular hydrogel hybridized with silver nanoparticles for antibacterial application. Soft Matter. 2018;14(7):1227-1234. doi: 10.1039/C7SM02251D
  157. Zheng Y, Yuan W, Liu H, Huang S, Bian L, Guo R. Injectable supramolecular gelatin hydrogel loading of resveratrol and histatin-1 for burn wound therapy. Biomater Sci. 2020;8(17):4810-4820. doi: 10.1039/D0BM00391C
  158. Zhai Z, Xu K, Mei L, et al. Co-assembled supramolecular hydrogels of cell adhesive peptide and alginate for rapid hemostasis and efficacious wound healing. Soft Matter. 2019;15(42):8603-8610. doi: 10.1039/C9SM01296F
  159. Preman NK, ES SP, Prabhu A, et al. Bioresponsive supramolecular hydrogels for hemostasis, infection control and accelerated dermal wound healing. J Mater Chem B. 2020;8(37):8585-8598. doi: 10.1039/D0TB01468K
  160. Wang W, Zeng Z, Xiang L, et al. Injectable self-healing hydrogel via biological environment-adaptive supramolecular assembly for gastric perforation healing. ACS Nano. 2021;15(6):9913-9923. doi: 10.1021/acsnano.1c01199
  161. Li Y, Zhu C, Dong Y, Liu D. Supramolecular hydrogels: mechanical strengthening with dynamics. Polymer. 2020;210:122993. doi: 10.1016/j.polymer.2020.122993
  162. Kim J-H, Park K, Nam HY, Lee S, Kim K, Kwon IC. Polymers for bioimaging. Prog Polym Sci. 2007;32(8-9): 1031-1053. doi: 10.1016/j.progpolymsci.2007.05.016
  163. Zhu Q, Qiu F, Zhu B, Zhu X. Hyperbranched polymers for bioimaging. Rsc Adv. 2013;3(7):2071-2083. doi: 10.1039/C2RA22210H
  164. Mehwish N, Dou X, Zhao Y, Feng C-L. Supramolecular fluorescent hydrogelators as bio-imaging probes. Mater Horiz. 2019;6(1):14-44. doi: 10.1039/C8MH01130C
  165. Gao F, Yang X, Song W. Bioinspired supramolecular hydrogel from design to applications. Small Methods. 2023:2300753. doi: 10.1002/smtd.202300753
  166. Völlmecke K, Afroz R, Bierbach S, et al. Hydrogel-based biosensors. Gels. 2022;8(12):768. doi: 10.3390/gels8120768
  167. Li F, Lyu D, Liu S, Guo W. DNA hydrogels and microgels for biosensing and biomedical applications. Adv Mater. 2020;32(3):1806538. doi: 10.1002/adma.201806538
  168. Lin X, Zhao X, Xu C, Wang L, Xia Y. Progress in the mechanical enhancement of hydrogels: fabrication strategies and underlying mechanisms. J Polym Sci. 2022;60(17): 2525-2542. doi: 10.1002/pol.20220154
  169. Omar J, Ponsford D, Dreiss CA, Lee TC, Loh XJ. Supramolecular hydrogels: design strategies and contemporary biomedical applications. Chem Asian J. 2022;17(9):e202200081. doi: 10.1002/asia.202200081
  170. Zou L, Su B, Addonizio CJ, Pramudya I, Webber MJ. Temperature-responsive supramolecular hydrogels by ternary complex formation with subsequent photo-crosslinking to alter network dynamics. Biomacromolecules. 2019;20(12):4512-4521.doi: 10.1021/acs.biomac.9b01267
  171. Yang B, Liang C, Chen D, et al. A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair. Bioact Mater. 2022;15:103-119. doi: 10.1016/j.bioactmat.2021.11.032
  172. Zhai X, Ma Y, Hou C, et al. 3D-printed high strength bioactive supramolecular polymer/clay nanocomposite hydrogel scaffold for bone regeneration. ACS Biomater Sci Eng. 2017;3(6):1109-1118. doi: 10.1021/acsbiomaterials.7b00224
  173. Jeong SH, Kim M, Kim TY, Kim H, Ju JH, Hahn SK. Supramolecular injectable hyaluronate hydrogels for cartilage tissue regeneration. ACS Appl Bio Mater. 2020;3(8):5040-5047. doi: 10.1021/acsabm.0c00537
  174. Andriamiseza F, Peters S, Roux C, Dietrich N, Coudret C, Fitremann J. Wet spinning and 3D printing of supramolecular hydrogels in acid-base and dynamic conditions. Colloids Surf A Physicochem Eng Asp. 2023;673:131765. doi: 10.1016/j.colsurfa.2023.131765
  175. Zhang X, Fan J, Lee C-S, Kim S, Chen C, Lee M. Supramolecular hydrogels based on nanoclay and guanidine-rich chitosan: injectable and moldable osteoinductive carriers. ACS Appl Bio Mater Interf. 2020;12(14):16088-16096. doi: 10.1021/acsami.0c01241
  176. Qin Z, Yu X, Wu H, Li J, Lv H, Yang X. Nonswellable and tough supramolecular hydrogel based on strong micelle crosslinkings. Biomacromolecules. 2019;20(9): 3399-3407. doi: 10.1021/acs.biomac.9b00666
  177. Li N, Liu C, Chen W. Facile access to guar gum based supramolecular hydrogels with rapid self-healing ability and multistimuli responsive gel–sol transitions. J Agric Food Chem. 2018;67(2):746-752. doi: 10.1021/acs.jafc.8b05130
Share
Back to top
International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing