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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Injectable hydrogels of enzyme-catalyzed cross-linked tyramine-modified gelatin for drug delivery

Yuanhan Tang https://orcid.org/0000-0002-4953-6696 A , Junjie Ding A , Xun Zhou A , Xintao Ma A , Yi Zhao A , Qiyu Mu A , Zixu Huang A , Qian Tao https://orcid.org/0000-0002-2212-2434 A * , Fangjie Liu B * and Ling Wang C *
+ Author Affiliations
- Author Affiliations

A School of Chemistry and Materials Science, Ludong University, Yantai, 264025, China.

B School of Food Engineering, Ludong University, Yantai, 264025, China.

C College of Chemistry and Chemical Engineering, Center of Cosmetics, Qilu Normal University, Jinan 250200, China.


Handling Editor: Charlotte Williams

Australian Journal of Chemistry 76(2) 88-99 https://doi.org/10.1071/CH22188
Submitted: 27 August 2022  Accepted: 3 February 2023   Published: 28 February 2023

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing.

Abstract

Enzymatically catalyzed cross-linking is a hydrogel fabrication method that generally is considered to have lower cytotoxicity than traditional chemical cross-linking methods. In order to optimize the properties of injectable hydrogels and expand their applications, an enzyme-catalyzed cross-linked injectable hydrogel was designed. The tyramine-modified gelatin (G-T) was formed into a stable injectable hydrogel by the combination of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) catalysis. 1H NMR spectroscopy was used to demonstrate the successful modification of gelatin by tyramine. The surface morphology of the prepared hydrogels was characterized jointly by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Rheological tests demonstrated the tunable mechanical strength, formation kinetics, shear thinning and good self-recovery properties of the hydrogels. In addition, the hydrogels can be formed into various shapes by injection. The hydrogel network structure is complex and interlaced, as such it is suitable to encapsulate drugs for controlled release. The drug release from the prepared hydrogels followed the Peppas–Sahlin model and belonged to Fickian diffusion. This study constructed injectable hydrogels through the enzyme-catalyzed cross-linking of modified gelatin and applied the hydrogels for drug release, which is expected to expand the application in biomedical fields.

Keywords: drug delivery, enzyme-catalyzed, gelatin, hydrogel rheology, injectable hydrogel, release kinetics, tyramine modification, self‐recovery.


References

[1]  D Yang, Recent advances in hydrogels. Chem Mater 2022, 34, 1987.
         | Recent advances in hydrogels.Crossref | GoogleScholarGoogle Scholar |

[2]  EM Ahmed, Hydrogel: preparation, characterization, and applications: a review. J Adv Res 2015, 6, 105.
         | Hydrogel: preparation, characterization, and applications: a review.Crossref | GoogleScholarGoogle Scholar |

[3]  J Luo, RM Maier, D Yu, B Liu, N Zhu, GL Amy, JC Crittenden, Double-network hydrogel: a potential practical adsorbent for critical metals extraction and recovery from water. Environ Sci Technol 2022, 56, 4715.
         | Double-network hydrogel: a potential practical adsorbent for critical metals extraction and recovery from water.Crossref | GoogleScholarGoogle Scholar |

[4]  X Zhang, Y Tang, P Wang, Y Wang, T Wu, T Li, S Huang, J Zhang, H Wang, S Ma, L Wang, W Xu, A review of recent advances in metal ion hydrogels: mechanism, properties and their biological applications. New J Chem 2022, 46, 13838.
         | A review of recent advances in metal ion hydrogels: mechanism, properties and their biological applications.Crossref | GoogleScholarGoogle Scholar |

[5]  Y Tang, H Wang, S Liu, L Pu, X Hu, J Ding, G Xu, W Xu, S Xiang, Z Yuan, A review of protein hydrogels: protein assembly mechanisms, properties, and biological applications. Colloids Surf B 2022, 220, 112973.
         | A review of protein hydrogels: protein assembly mechanisms, properties, and biological applications.Crossref | GoogleScholarGoogle Scholar |

[6]  Y Xiong, X Zhang, X Ma, W Wang, F Yan, X Zhao, X Chu, W Xu, C Sun, A review of the properties and applications of bioadhesive hydrogels. Polym Chem 2021, 12, 3721.
         | A review of the properties and applications of bioadhesive hydrogels.Crossref | GoogleScholarGoogle Scholar |

[7]  W Xu, Z Zhang, X Zhang, Y Tang, Y Niu, X Chu, S Zhang, C Ren, Peptide hydrogel with antibacterial performance induced by rare Earth metal ions. Langmuir 2021, 37, 12842.
         | Peptide hydrogel with antibacterial performance induced by rare Earth metal ions.Crossref | GoogleScholarGoogle Scholar |

[8]  Y Tang, X Zhang, X Li, C Ma, X Chu, L Wang, W Xu, A review on recent advances of protein-polymer hydrogels. Eur Polym J 2022, 162, 110881.
         | A review on recent advances of protein-polymer hydrogels.Crossref | GoogleScholarGoogle Scholar |

[9]  Z Li, W Xu, X Wang, W Jiang, X Ma, F Wang, C Zhang, C Ren, Fabrication of PVA/PAAm IPN hydrogel with high adhesion and enhanced mechanical properties for body sensors and antibacterial activity. Eur Polym J 2021, 146, 110253.
         | Fabrication of PVA/PAAm IPN hydrogel with high adhesion and enhanced mechanical properties for body sensors and antibacterial activity.Crossref | GoogleScholarGoogle Scholar |

[10]  W Xu, Y Hong, A Song, J Hao, Peptide-assembled hydrogels for pH-controllable drug release. Colloids Surf B 2020, 185, 110567.
         | Peptide-assembled hydrogels for pH-controllable drug release.Crossref | GoogleScholarGoogle Scholar |

[11]  S Huang, X Kong, Y Xiong, X Zhang, H Chen, W Jiang, Y Niu, W Xu, C Ren, An overview of dynamic covalent bonds in polymer material and their applications. Eur Polym J 2020, 141, 110094.
         | An overview of dynamic covalent bonds in polymer material and their applications.Crossref | GoogleScholarGoogle Scholar |

[12]  Z Li, X Meng, W Xu, S Zhang, J Ouyang, Z Zhang, Y Liu, Y Niu, S Ma, Z Xue, A Song, S Zhang, C Ren, Single network double cross-linker (SNDCL) hydrogels with excellent stretchability, self-recovery, adhesion strength, and conductivity for human motion monitoring. Soft Matter 2020, 16, 7323.
         | Single network double cross-linker (SNDCL) hydrogels with excellent stretchability, self-recovery, adhesion strength, and conductivity for human motion monitoring.Crossref | GoogleScholarGoogle Scholar |

[13]  W Du, Z Zhao, X Zhang, Sodium alginate crosslinker engineered UCST hydrogel towards superior mechanical properties and controllable dye removal. Carbohydr Polym 2022, 285, 119232.
         | Sodium alginate crosslinker engineered UCST hydrogel towards superior mechanical properties and controllable dye removal.Crossref | GoogleScholarGoogle Scholar |

[14]  J Berger, M Reist, JM Mayer, O Felt, NA Peppas, R Gurny, Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm 2004, 57, 19.
         | Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications.Crossref | GoogleScholarGoogle Scholar |

[15]  D Sun, H Wang, J Liu, X Wang, H Guo, L Xue, L Li, J Li, B Zhang, Y Xue, S Li, Y Liu, An enzyme cross-linked hydrogel as a minimally invasive arterial tissue sealing and anti-adhesion barrier. Nano Today 2022, 44, 101467.
         | An enzyme cross-linked hydrogel as a minimally invasive arterial tissue sealing and anti-adhesion barrier.Crossref | GoogleScholarGoogle Scholar |

[16]  G He, H Lei, W Sun, J Gu, W Yu, D Zhang, H Chen, Y Li, M Qin, B Xue, W Wang, Y Cao, Strong and reversible covalent double network hydrogel based on force-coupled enzymatic reactions. Angew Chem Int Ed 2022, 61, e202201765.
         | Strong and reversible covalent double network hydrogel based on force-coupled enzymatic reactions.Crossref | GoogleScholarGoogle Scholar |

[17]  B Elham, M Hosseini, M Mohajer, S Hassanzadeh, S Saghati, J Hilborn, M Khanmohammadi, Enzymatic crosslinked hydrogels for biomedical application. Polym Sci Ser A 2022, 63, S1.
         | Enzymatic crosslinked hydrogels for biomedical application.Crossref | GoogleScholarGoogle Scholar |

[18]  M Khanmohammadi, MB Dastjerdi, A Ai, A Ahmadi, A Godarzi, A Rahimi, J Ai, Horseradish peroxidase-catalyzed hydrogelation for biomedical applications. Biomater Sci 2018, 6, 1286.
         | Horseradish peroxidase-catalyzed hydrogelation for biomedical applications.Crossref | GoogleScholarGoogle Scholar |

[19]  Z Peng, Y She, L Chen, Synthesis of poly(glutamic acid)-tyramine hydrogel by enzyme-mediated gelation for controlled release of proteins. J Biomater Sci Polym Ed 2015, 26, 111.
         | Synthesis of poly(glutamic acid)-tyramine hydrogel by enzyme-mediated gelation for controlled release of proteins.Crossref | GoogleScholarGoogle Scholar |

[20]  IM Oliveira, C Gonçalves, ME Shin, S Lee, RL Reis, G Khang, JM Oliveira, Enzymatically crosslinked tyramine-gellan gum hydrogels as drug delivery system for rheumatoid arthritis treatment. Drug Deliv Transl Res 2021, 11, 1288.
         | Enzymatically crosslinked tyramine-gellan gum hydrogels as drug delivery system for rheumatoid arthritis treatment.Crossref | GoogleScholarGoogle Scholar |

[21]  BD Zheng, J Ye, YC Yang, YY Huang, MT Xiao, Self-healing polysaccharide-based injectable hydrogels with antibacterial activity for wound healing. Carbohydr Polym 2022, 275, 118770.
         | Self-healing polysaccharide-based injectable hydrogels with antibacterial activity for wound healing.Crossref | GoogleScholarGoogle Scholar |

[22]  C Zhou, X Zhao, Y Xiong, Y Tang, X Ma, Q Tao, C Sun, W Xu, A review of etching methods of MXene and applications of MXene conductive hydrogels. Eur Polym J 2022, 167, 111063.
         | A review of etching methods of MXene and applications of MXene conductive hydrogels.Crossref | GoogleScholarGoogle Scholar |

[23]  Y Yan, Y Li, Z Zhang, X Wang, Y Niu, S Zhang, W Xu, C Ren, Advances of peptides for antibacterial applications. Colloids Surf B 2021, 202, 111682.
         | Advances of peptides for antibacterial applications.Crossref | GoogleScholarGoogle Scholar |

[24]  X Ma, X Zhou, J Ding, B Huang, P Wang, Y Zhao, Q Mu, S Zhang, C Ren, W Xu, Hydrogels for underwater adhesion: adhesion mechanism, design strategies and applications. J Mater Chem A 2022, 10, 11823.
         | Hydrogels for underwater adhesion: adhesion mechanism, design strategies and applications.Crossref | GoogleScholarGoogle Scholar |

[25]  Y Zhao, S Song, X Ren, J Zhang, Q Lin, Y Zhao, Supramolecular adhesive hydrogels for tissue engineering applications. Chem Rev 2022, 122, 5604.
         | Supramolecular adhesive hydrogels for tissue engineering applications.Crossref | GoogleScholarGoogle Scholar |

[26]  J Zhou, H Zhang, MS Fareed, Y He, Y Lu, C Yang, Z Wang, J Su, P Wang, W Yan, K Wang, An injectable peptide hydrogel constructed of natural antimicrobial peptide J-1 and ADP shows anti-infection, hemostasis, and antiadhesion efficacy. ACS Nano 2022, 16, 7636.
         | An injectable peptide hydrogel constructed of natural antimicrobial peptide J-1 and ADP shows anti-infection, hemostasis, and antiadhesion efficacy.Crossref | GoogleScholarGoogle Scholar |

[27]  LR Khoury, M Slawinski, DR Collison, I Popa, Cation-induced shape programming and morphing in protein-based hydrogels. Sci Adv 2020, 6, eaba6112.
         | Cation-induced shape programming and morphing in protein-based hydrogels.Crossref | GoogleScholarGoogle Scholar |

[28]  W Qiu, Q Wang, M Li, N Li, X Wang, J Yu, F Li, D Wu, 3D hybrid scaffold with aligned nanofiber yarns embedded in injectable hydrogels for monitoring and repairing chronic wounds. Compos B Eng 2022, 234, 109688.
         | 3D hybrid scaffold with aligned nanofiber yarns embedded in injectable hydrogels for monitoring and repairing chronic wounds.Crossref | GoogleScholarGoogle Scholar |

[29]  Y Li, R Fu, Z Duan, C Zhu, D Fan, Injectable hydrogel based on defect-rich multi-nanozymes for diabetic wound healing via an oxygen self-supplying cascade reaction. Small 2022, 18, 2200165.
         | Injectable hydrogel based on defect-rich multi-nanozymes for diabetic wound healing via an oxygen self-supplying cascade reaction.Crossref | GoogleScholarGoogle Scholar |

[30]  Y Lei, Y Wang, J Shen, Z Cai, C Zhao, H Chen, X Luo, N Hu, W Cui, W Huang, Injectable hydrogel microspheres with self-renewable hydration layers alleviate osteoarthritis. Sci Adv 2022, 8, eabl6449.
         | Injectable hydrogel microspheres with self-renewable hydration layers alleviate osteoarthritis.Crossref | GoogleScholarGoogle Scholar |

[31]  JM Alonso, J Andrade Del Olmo, R Perez Gonzalez, V Saez-Martinez, Injectable hydrogels: from laboratory to industrialization. Polymers 2021, 13, 650.
         | Injectable hydrogels: from laboratory to industrialization.Crossref | GoogleScholarGoogle Scholar |

[32]  Z Zhao, G Li, H Ruan, K Chen, Z Cai, G Lu, R Li, L Deng, M Cai, W Cui, Capturing magnesium Ions via microfluidic hydrogel microspheres for promoting cancellous bone regeneration. ACS Nano 2021, 15, 13041.
         | Capturing magnesium Ions via microfluidic hydrogel microspheres for promoting cancellous bone regeneration.Crossref | GoogleScholarGoogle Scholar |

[33]  X Chen, B Tan, S Wang, R Tang, Z Bao, G Chen, S Chen, W Tang, Z Wang, C Long, WW Lu, D Yang, L Bian, S Peng, Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions. Biomaterials 2021, 274, 120895.
         | Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions.Crossref | GoogleScholarGoogle Scholar |

[34]  IM Oliveira, MR Carvalho, DC Fernandes, CM Abreu, FR Maia, H Pereira, D Caballero, SC Kundu, RL Reis, JM Oliveira, Modulation of inflammation by anti-TNF α mAb-dendrimer nanoparticles loaded in tyramine-modified gellan gum hydrogels in a cartilage-on-a-chip model. J Mater Chem B 2021, 9, 4211.
         | Modulation of inflammation by anti-TNF α mAb-dendrimer nanoparticles loaded in tyramine-modified gellan gum hydrogels in a cartilage-on-a-chip model.Crossref | GoogleScholarGoogle Scholar |

[35]  Z Guo, M Yao, H Sun, M Shi, X Dong, S He, B Guo, F Yao, H Zhang, J Li, Tyramine-enhanced zwitterion hyaluronan hydrogel coating for anti-fouling and anti-thrombosis. Sci China Technol Sci 2022, 65, 1828.
         | Tyramine-enhanced zwitterion hyaluronan hydrogel coating for anti-fouling and anti-thrombosis.Crossref | GoogleScholarGoogle Scholar |

[36]  B Bi, H Liu, W Kang, R Zhuo, X Jiang, An injectable enzymatically crosslinked tyramine-modified carboxymethyl chitin hydrogel for biomedical applications. Colloids Surf B 2019, 175, 614.
         | An injectable enzymatically crosslinked tyramine-modified carboxymethyl chitin hydrogel for biomedical applications.Crossref | GoogleScholarGoogle Scholar |

[37]  T Fukuoka, H Uyama, S Kobayashi, Polymerization of polyfunctional macromolecules: synthesis of a new class of high molecular weight poly(amino acid)s by oxidative coupling of phenol-containing precursor polymers. Biomacromolecules 2004, 5, 977.
         | Polymerization of polyfunctional macromolecules: synthesis of a new class of high molecular weight poly(amino acid)s by oxidative coupling of phenol-containing precursor polymers.Crossref | GoogleScholarGoogle Scholar |

[38]  Z Zhou, G Li, N Wang, F Guo, L Guo, X Liu, Synthesis of temperature/pH dual-sensitive supramolecular micelles from β-cyclodextrin-poly(N-isopropylacrylamide) star polymer for drug delivery. Colloids Surf B 2018, 172, 136.
         | Synthesis of temperature/pH dual-sensitive supramolecular micelles from β-cyclodextrin-poly(N-isopropylacrylamide) star polymer for drug delivery.Crossref | GoogleScholarGoogle Scholar |

[39]  Y Zhang, M Huo, J Zhou, A Zou, W Li, C Yao, S Xie, DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J 2010, 12, 263.
         | DDSolver: an add-in program for modeling and comparison of drug dissolution profiles.Crossref | GoogleScholarGoogle Scholar |

[40]  C Sethy, CN Kundu, 5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: implication of DNA repair inhibition. Biomed Pharmacother 2021, 137, 111285.
         | 5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: implication of DNA repair inhibition.Crossref | GoogleScholarGoogle Scholar |

[41]  Q Tao, J Zhong, R Wang, Y Huang, Ionic and enzymatic multiple-crosslinked nanogels for drug delivery. Polymers 2021, 13, 3565.
         | Ionic and enzymatic multiple-crosslinked nanogels for drug delivery.Crossref | GoogleScholarGoogle Scholar |

[42]  S Ghafouri-Fard, A Abak, F Tondro Anamag, H Shoorei, F Fattahi, SA Javadinia, A Basiri, M Taheri, 5-Fluorouracil: a narrative review on the role of regulatory mechanisms in driving resistance to this chemotherapeutic agent. Front Oncol 2021, 11, 658636.
         | 5-Fluorouracil: a narrative review on the role of regulatory mechanisms in driving resistance to this chemotherapeutic agent.Crossref | GoogleScholarGoogle Scholar |

[43]  NA Peppas, JJ Sahlin, A simple equation for the description of solute release. III. Coupling of diffusion and relaxation. Int J Pharm 1989, 57, 169.
         | A simple equation for the description of solute release. III. Coupling of diffusion and relaxation.Crossref | GoogleScholarGoogle Scholar |