ساخت و مشخصه‌یابی هیدروژل کامپوزیتی فیبروئین ابریشم اصلاح شده/ چارچوب فلزی– آلی مبتنی بر روی با استفاده از واکنش فنتون برای کاربردهای پزشکی

نوع مقاله : مقاله پژوهشی

نویسندگان

دانشکده مهندسی مواد، دانشگاه صنعتی اصفهان، اصفهان، ایران

چکیده

مقدمه و اهداف: هیدروژل‌ها به‌عنوان داربست‌های سه‌بعدی آب‌دوست، نقش مهمی در جذب مایعات زیستی و ایجاد پایداری مکانیکی در فرآیند بازسازی بافت ایفا می‌کنند. هدف این پژوهش، طراحی و سنتز هیدروژل‌های کامپوزیتی جدیدی بر پایه فیبروئین ابریشم اصلاح‌شده با گروه‌های تیول و چارچوب فلزی-آلی (Zn-Bio MOF) حاوی یون روی و لیگاند آدنین، به‌منظور بهبود خواص مکانیکی و زیستی برای کاربردهای مهندسی بافت است.
مواد و روش‌ها: فیبروئین ابریشم خالص استخراج و با افزودن گروه‌های تیول از طریق اتصال ال-سیستئین اصلاح شد. برای تأیید این اصلاحات، طیف‌سنجی مادون‌قرمز تبدیل فوریه انجام شد.Zn-Bio MOF  نیز از طریق فرآیند هیدروترمال با یون روی (II) و لیگاند آدنین سنتز شد. سه نوع هیدروژل کامپوزیتی تهیه شد: (1) هیدروژل بر پایه فیبروئین ابریشم اصلاح‌شده، (2) هیدروژل بر پایه فیبروئین ابریشم اصلاح‌شده ژل‌شده با واکنش فنتون و (3) هیدروژل کامپوزیتی حاوی Zn-Bio MOF در غلظت‌های مختلف. برای مشخصه‌یابی، از میکروسکوپ الکترونی روبشی و پراش پرتو ایکس استفاده شد.
یافته‌ها: نتایج طیف‌سنجی مادون‌قرمز تبدیل فوریه کاهش شدت پیک‌های cm⁻¹ 1650 و cm⁻¹ 3300 و ظهور پیک‌های جدید مربوط به پیوندهای S-S و S-H را تأیید کرد. میانگین قطر نانوذرات Zn-Bio MOF برابر با 0/12±0/39 نانومتر و مساحت سطح ویژه آن 1138/3 مترمربع بر گرم بود. بررسی خواص تورم و تخریب نشان داد که هیدروژل‌های حاوی نانوذرات Zn-Bio MOF دارای مدول فشاری و چقرمگی بالاتر، کاهش وزن حدود 30 درصد طی 72 ساعت، و رفتار تورمی کنترل‌شده بودند.
نتیجه‌گیری: نتایج این پژوهش نشان می‌دهد که هیدروژل‌های کامپوزیتی Zn-Bio MOF به دلیل بهبود خواص مکانیکی و کنترل تورم، پتانسیل بالایی برای استفاده در مهندسی بافت و کاربردهای زیستی دارند.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

Fabrication and Characterization of Modified Silk Fibroin/Zinc-Based Metal-Organic Framework Composite Hydrogel Using Fenton Reaction for Medical Applications

نویسندگان [English]

  • Mohammad Kian Vojdanpak
  • Kiana Mohagheghian
  • Mahshid Kharaziha
Department of Materials Engineering, Isfahan University of Technology, Isfahan, Iran
چکیده [English]

Introduction and Objectives: Hydrogels, as three-dimensional hydrophilic scaffolds, play a crucial role in absorbing biological fluids and providing mechanical stability in the tissue regeneration process. This study aims to design and synthesize novel composite hydrogels based on thiol-modified silk fibroin and a zinc-containing bio-metal-organic framework (Zn-Bio MOF) with an adenine ligand to enhance mechanical and biological properties for tissue engineering applications.
Materials and Methods: Pure silk fibroin was extracted and modified with thiol groups via L-cysteine conjugation. Fourier-transform infrared (FTIR) spectroscopy was conducted to confirm these modifications. The Zn-Bio MOF was synthesized through a hydrothermal process using zinc (II) ions and an adenine ligand. Three types of composite hydrogels were prepared: (1) hydrogel based on thiol-modified silk fibroin, (2) hydrogel based on thiol-modified silk fibroin crosslinked via the Fenton reaction, and (3) composite hydrogel containing Zn-Bio MOF at various concentrations. Material characterization was performed using scanning electron microscopy (SEM) and X-ray diffraction (XRD).
Results: FTIR spectroscopy confirmed the reduction in peak intensities at 1650 cm⁻¹ and 3300 cm⁻¹ and the appearance of new peaks corresponding to S-S and S-H bonds. The average particle size of Zn-Bio MOF was 0.39 ± 0.12 nm, with a specific surface area of 1138.3 m²/g. Swelling and degradation analyses indicated that Zn-Bio MOF-containing hydrogels exhibited improved mechanical properties, including higher compressive modulus and toughness, approximately 30% weight loss over 72 hours, and controlled swelling behavior.
Conclusion: The findings of this study suggest that Zn-Bio MOF composite hydrogels, due to their enhanced mechanical properties and controlled swelling behavior, hold significant potential for tissue engineering and biomedical applications.

کلیدواژه‌ها [English]

  • Silk
  • Metal-organic framework
  • Zinc
  • Fenton reaction
  • Hydrogel
  1. Kaur H, Gogoi B, Sharma I, Das DK, Azad MA, Pramanik D Das, et al. Hydrogels as a Potential Biomaterial for Multimodal Therapeutic Applications. Mol Pharm. 2024;21(10):4827–48. https://doi.org/10. 1021/acs.molpharmaceut.4c00595
  2. Wagh P, Nawani DN, Vaidya DV. Hydrogels: a versatile biomaterial revolutionizing science and applications. In: Futuristic trends in biotechnology. Volume 3, Book 10 [Internet]. Iterative International Publisher, Selfypage Developers Pvt Ltd; 2024. p. 27–35. https://www.iipseries.org/viewpaper.php?pid=1027&pt=hydrogels-a-versatile-biomaterial-revolutionizing-science-and-applications
  3. Madappura AP, Madduri S. A comprehensive review of silk-fibroin hydrogels for cell and drug delivery applications in tissue engineering and regenerative Comput Struct Biotechnol J. 2023;21:4868–86. https://linkinghub.elsevier.com/retrieve/pii/S2001037023003689
  4. Zheng H, Zuo B. Functional silk fibroin hydrogels: preparation, properties and applications. J Mater Chem B. 2021;9(5):1238–58. http://xlink.rsc.org/ ?DOI=D0TB02099K
  5. Qi Z, Tao X, Tan G, Tian B, Zhang L, Kundu SC, et al. Electro-responsive silk fibroin microneedles for controlled release of insulin. Int J Biol Macromol. 2023; 242: 124684. https://linkinghub.elsevier.com/ retrieve/pii/S0141813023015787
  6. Liang J, Zhang X, Chen Z, Li S, Yan C. Thiol–Ene Click Reaction Initiated Rapid Gelation of PEGDA/Silk Fibroin Hydrogels. Polymers (Basel). 2019;11(12):2102. https://www.mdpi.com/2073-4360/11/12/2102
  7. Zhang W, Liu C, Liu Z, Zhao C, Zhu J, Ren J, et al. A Cell Selective Fluoride-Activated MOF Biomimetic Platform for Prodrug Synthesis and Enhanced Synergistic Cancer Therapy. 2022;16(12):20975–20984. https://doi.org/10.1021/acsnano.2c08604
  8. Bahrani S, Hashemi SA, Mousavi SM, Azhdari R. Zinc-based metal–organic frameworks as nontoxic and biodegradable platforms for biomedical applications: review study. Drug Metab Rev [Internet]. 2019;51(3): 356–77. https://www.tandfonline.com/doi/full/10.1080/ 03602532.2019.1632887
  9. Jasim SA, Amin HIM, Rajabizadeh A, Nobre MAL, Borhani F, Jalil AT, et al. Synthesis characterization of Zn-based MOF and their application in degradation of water contaminants. Water Sci Technol. 2022; 86(9): 2303–35. https://doi.org/10.2166/wst.2022.318
  10. Moharramnejad M, Ehsani A, Salmani S, Shahi M, Malekshah RE, Robatjazi ZS, et al. Zinc-based metal-organic frameworks: synthesis and recent progress in biomedical application. J Inorg Organomet Polym Mater. 2022;32(9):3339–54. https://link.springer.com/10.1007/s10904-022-02385-y
  11. Dong JP, Shi ZZ, Li B, Wang LY. Synthesis of a novel 2D zinc( ii ) metal–organic framework for photocatalytic degradation of organic dyes in water. Dalt Trans. 2019;48(47):17626–32. https://doi.org/10.1039/C9DT03727F
  12. Saboorizadeh B, Zare-Dorabei R, Safavi M, Safarifard V. Applications of Metal–Organic Frameworks (MOFs) in Drug Delivery, Biosensing, and Therapy: A Comprehensive Review. Langmuir. 2024;40(43):22477–503. https://pubs.acs.org/doi/10. 1021/acs.langmuir.4c02795
  13. Khafaga DSR, El-Morsy MT, Faried H, Diab AH, Shehab S, Saleh AM, et al. Metal-organic frameworks in drug delivery: engineering versatile platforms for therapeutic applications. RSC Adv. 2024; 14(41):30201–29. https://doi.org/10.1039/D4RA04441J
  14. Qiao M, Xu Z, Pei X, Liu Y, Wang J, Chen J, et al. Nano SIM@ZIF-8 modified injectable High-intensity biohydrogel with bidirectional regulation of osteogenesis and Anti-adipogenesis for bone repair. Chem Eng J. 2022;434:134583. https://linkinghub.elsevier.com/ retrieve/pii/S1385894722000912
  15. Li X, Meng Z, Guan L, Liu A, Li L, Nešić MD, et al. Glucose-Responsive hydrogel optimizing Fenton reaction to eradicate multidrug-resistant bacteria for infected diabetic wound healing. Chem Eng J. 2024; 487:150545. https://linkinghub.elsevier.com/retrieve/ pii/S1385894724020321
  16. Choi J, Hastürk O, Mu X, Sahoo JK, Kaplan D. Silk Hydrogels with Controllable Formation of Dityrosine, 3,4-Dihydroxyphenylalanine, and 3,4-Dihydroxyphenylalanine–Fe3+ Complexes through Chitosan Particle-Assisted Fenton Reactions. Biomacromolecules. 2021;22. https://doi.org/10.1021/ acs.biomac.0c01539
  17. Choi J, McGill M, Raia NR, Hasturk O, Kaplan DL. Silk Hydrogels Crosslinked by the Fenton Reaction. Adv Healthc Mater. 2019; 8(17):e1900644. https:// doi.org/10.1002/adhm.201900644
  18. Barros JAG, Fechine GJM, Alcantara MR, Catalani LH. Poly(N-vinyl-2-pyrrolidone) hydrogels produced by Fenton reaction. Polymer (Guildf). 2006;47(26): 8414–9. https://linkinghub.elsevier.com/retrieve/pii/ S0032386106012134
  19. Qin G, Rivkin A, Lapidot S, Hu X, Preis I, Arinus SB, et al. Recombinant exon-encoded resilins for elastomeric biomaterials. Biomaterials. 2011;32(35): 9231–43. https://linkinghub.elsevier.com/retrieve/pii/ S0142961211006752
  20. Sun L, Zhang S, Zhang J, Wang N, Liu W, Wang W. Fenton reaction-initiated formation of biocompatible injectable hydrogels for cell encapsulation. J Mater Chem B. 2013;1(32):3932. https://doi.org/10.1039/ C3TB20553C
  21. Teimouri A, Ghorbanian L, Najafi Chermahini A, Emadi R. Fabrication and characterization of silk/forsterite composites for tissue engineering applications. Ceram Int. 2014;40(5):6405–11. https://linkinghub.elsevier.com/retrieve/pii/S0272884213016672
  22. Talusig JM, Murphy AR. Synthesis and Characterization of Highly Thiolated Silk Fibroin. Macromol Chem Phys. 2023;225(4): https://onlinelibrary.wiley.com/doi/10.1002/macp.202300340
  23. Nogueira F, Granadeiro L, Mouro C, Gouveia IC. Antimicrobial and antioxidant surface modification toward a new silk-fibroin (SF)-l-Cysteine material for skin disease management. Appl Surf Sci.2016;364:552–9. https://linkinghub.elsevier.com/retrieve/pii/S0169433215031797
  24. Florczak A, Jastrzebska K, Bialas W, Mackiewicz A, Dams-Kozlowska H. Optimization of spider silk sphere formation processing conditions to obtain carriers with controlled characteristics. J Biomed Mater Res A. 2018;106(12):3211–21. https://doi.org/ 10.1002/jbm.a.36516
  25. Yang Q, Xu Q, Jiang HL. Metal–organic frameworks meet metal nanoparticles: synergistic effect for enhanced catalysis. Chem Soc Rev. 2017;46(15): 4774–808. http://dx.doi.org/10.1039/C6CS00724D
  26. Lucena GN, Alves RC, Abuçafy MP, Chiavacci LA, da Silva IC, Pavan FR, et al. Zn-based porous coordination solid as diclofenac sodium carrier. J Solid State Chem. 2018;260:67–72. https://www. sciencedirect.com/science/article/pii/S0022459618300203
  27. Lu H, Tian H, Wang C, Xu S. Designing and controlling the morphology of spherical molecularly imprinted polymers. Mater Adv. 2020;1(7):2182–201. https://xlink.rsc.org/?DOI=D0MA00415D
  28. Khoshhal S, Ghoreyshi AA, Jahanshahi M, Mohammadi M. Study of the temperature and solvent content effects on the structure of Cu–BTC metal organic framework for hydrogen storage. RSC Adv. 2015;5(31):24758–68. http://dx.doi.org/10.1039/C5RA01890K
  29. Mikšík F, Miyazaki T, Thu K. Adsorption Isotherm Modelling of Water on Nano-Tailored Mesoporous Silica Based on Distribution Function. Energies [Internet]. 2020;13(16):4247. https://www.mdpi.com/ 1996-1073/13/16/4247
  30. Yamada T. Iron-Catalyzed C–H Alkylamination of Tyrosine Derivatives. Org Lett. 2024;26(25): 5358–63. https://pubs.acs.org/doi/10.1021/acs.orglett.4c01764
  31. Gao Y, Peng K, Mitragotri S. Covalently Crosslinked Hydrogels via Step‐Growth Reactions: Crosslinking Chemistries, Polymers, and Clinical Impact. Adv Mater. 2021;33(25). https://onlinelibrary.wiley.com/ doi/10.1002/adma.202006362
  32. Zhang X, Bao H, Donley C, Liang J, Yang S, Xu S. Thiolation and characterization of regenerated Bombyx mori silk fibroin films with reduced glutathione. BMC Chem. 2019;13(1):62. https://bmcchem.biomedcentral.com/articles/10.1186/s13065-019-0583-x
  33. Kohar R, Ghosh M, Sawale JA, Singh A, Rangra NK, Bhatia R. Insights into Translational and Biomedical Applications of Hydrogels as Versatile Drug Delivery Systems. AAPS PharmSciTech. 2024; 25(1):17. https://link.springer.com/10.1208/s12249-024-02731-y
  34. Zirehpour A, Rahimpour A, Khoshhal S, Firouzjaei MD, Ghoreyshi AA. The impact of MOF feasibility to improve the desalination performance and antifouling properties of FO membranes. RSC Adv. 2016;6(74): 70174–85. https://xlink.rsc.org/?DOI=C6RA14591D
  35. Collins MN, Birkinshaw C. Morphology of crosslinked hyaluronic acid porous hydrogels. J Appl Polym Sci. 2011;120(2):1040–9. https://onlinelibrary.wiley.com/doi/ 10.1002/app.33241
  36. Song J, Gerecht S. Hydrogels to Recapture Extracellular Matrix Cues That Regulate Vascularization. Arterioscler Thromb Vasc Biol. 2023;43(8). https://www.ahajournals. org/doi/10.1161/ATVBAHA.122.318235
  37. Li Q, Ma W, Ma H, Shang H, Qiao N, Sun X. Synthesis and Characterization of Temperature‐/pH‐Responsive Hydrogels for Drug Delivery. ChemistrySelect. 2023; 8(3). https://chemistry-europe.onlinelibrary.wiley.com/ doi/10.1002/slct.202204270
  38. Zareie C, Seifi A, Bahramian AR. Double networks hybrid hydrogels of silica nanoparticles/polyacrylamide: Network stiffness, viscoelastic, mechanical and adhesion properties. J Dispers Sci Technol. 2024;1–11. https://www.tandfonline.com/doi/full/10.1080/01932691.2024.2342434
  39. Wang Q, Zhang Y, Ma Y, Wang M, Pan G. Nano-crosslinked dynamic hydrogels for biomedical applications. Mater Today Bio. 2023;20:100640. https://linkinghub.elsevier.com/retrieve/pii/S259000642300100X
  40. Su D, Jiang L, Chen X, Dong J, Shao Z. Enhancing the gelation and bioactivity of injectable silk fibroin hydrogel with laponite nanoplatelets. ACS Appl Mater Interfaces. 2016;8(15):9619–28. https://doi. org/10.1021/acsami.6b00891
  41. Haghighattalab M, Kajbafzadeh A, Baghani M, Gharehnazifam Z, Jobani BM, Baniassadi M. Silk Fibroin Hydrogel Reinforced With Magnetic Nanoparticles as an Intelligent Drug Delivery System for Sustained Drug Release. Front Bioeng Biotechnol. 2022;10. https://www.frontiersin.org/ articles/10.3389/fbioe.2022.891166/full

 

 

 

 

ارتقاء امنیت وب با وف ایرانی