تهیه و مشخصه‌یابی فیلم‌های کامپوزیتی پایه هیالورونیک اسید برای کاربردهای زخم‌پوش

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه بیومواد، پژوهشکده نانو و مواد پیشرفته، پژوهشگاه مواد و انرژی، البرز، ایران

2 گروه محیط زیست و انرژی، پژوهشکده انرژی، پژوهشگاه مواد و انرژی، البرز، ایران

3 گروه نانومواد، پژوهشکده نانو و مواد پیشرفته، پژوهشگاه مواد و انرژی، البرز، ایران

4 گروه پوست، مرکز تحقیقات پوست و سلول های بنیادی، دانشگاه علوم پزشکی تهران، تهران، ایران

چکیده

مقدمه و اهداف: هیالورونیک اسید، به‌دلیل ویژگی‌های زیست‌سازگاری، نگهداشت رطوبت و ترمیم زخم، یکی از مواد پرکاربرد در زخم‌پوش‌ها است؛ اما محدودیت‌هایی نظیر ضعف مکانیکی، پایداری پایین در محیط مرطوب و فقدان خاصیت ضدباکتریایی دارد. در این پژوهش، با هدف ارتقاء کارایی این فیلم‌ها، از ترکیب هیالورونیک اسید با کیتوسان  و به‌کارگیری گلوتارآلدئید و تانیک اسید به‌عنوان عوامل پیوند عرضی استفاده شده است. نوآوری اصلی این تحقیق، استفاده هم‌زمان از دو عامل اصلاح شیمیایی است.
مواد و روش‌ها: فیلم‌های کامپوزیتی هیالورونیک اسید/ کیتوسان با نسبت مشخص ترکیب و با استفاده از گلوتارآلدئید و تانیک اسید اصلاح شدند. آنالیز طیف‌سنجی مادون قرمز تبدیل فوریه برای بررسی برهم‌کنش‌های شیمیایی و ساختار پیوندها، آزمون کشش برای ارزیابی خواص مکانیکی و آزمون‌های زاویه تماس، جذب آب، سمیت سلولی و ضدباکتری، برای بررسی عملکرد زیستی فیلم‌ها انجام شد.
یافته‌ها: طیف‌سنجی مادون قرمز تبدیل فوریه بیانگر تشکیل پیوندهای جدید و ساختار شبکه‌ای پایدار در اثر اصلاح شیمیایی بود. نمونه‌های اصلاح‌شده مدول یانگ 2-1/5 MPa، تنش کششی MPa 2 و زاویه تماس 45 درجه از خود نشان دادند که نشانگر افزایش استحکام و آب‌دوستی است. درصد جذب آب بالا (733 درصد) و بقای سلولی 85–90 درصد در غلظت بهینه گلوتارآلدئید، دلالت بر زیست‌سازگاری مطلوب دارد. با‌این‌حال، خواص ضدباکتریایی قابل‌توجهی مشاهده نشد.
نتیجه‌گیری: نتایج این تحقیق نشان می‌دهد که استفاده ترکیبی از کیتوسان و عوامل پیوند عرضی گلوتارآلدئید و تانیک اسید، منجر به بهبود چشمگیر خواص مکانیکی، آب‌دوستی و زیست‌سازگاری فیلم‌های هیالورونیک اسید شده و آن‌ها را به گزینه‌ای مناسب برای کاربرد در زخم‌پوش‌ها تبدیل کرده است. برای افزایش اثربخشی ضدباکتریایی، پیشنهاد می‌شود از نانوذرات با خاصیت ضدباکتری استفاده شود.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

Preparation and Characterization of Hyaluronic Acid-based Composite Films for Wound Dressing Applications

نویسندگان [English]

  • Farhad Ahmadi 1
  • Seyed Mojtaba Hosseini Fard 2
  • Mohammad Reza Vaezi Jazeh 3
  • Leila Mohammadi 3
  • Mohammad Ali Nilforoushzadeh 4
1 Biomaterials Group, Nano and Advanced Materials Research Institute, Materials and Energy Research Center, Alborz, Iran
2 Environmental and Energy Group, Energy Research Institute, Materials and Energy Research Center, Alborz, Iran
3 Nanomaterials Group, Nano and Advanced Materials Research Institute, Materials and Energy Research Center, Alborz, Iran
4 Dermatology Group, Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
چکیده [English]

Introduction and Objectives: Hyaluronic acid is widely used in wound dressings due to its biocompatibility, moisture retention, and wound healing properties. However, its poor mechanical strength, limited stability in moist environments, and insufficient antibacterial activity restrict its clinical applications. This study aims to improve the performance of hyaluronic acid -based films by incorporating chitosan and employing glutaraldehyde and tannic acid as dual crosslinking agents. The novelty of this work lies in the simultaneous use of the two chemical modifiers.
Materials and Methods: Composite films were prepared by blending hyaluronic acid and chitosan at a defined ratio and chemically modified using glutaraldehyde and tannic acid. FTIR spectroscopy was used to evaluate chemical interactions and bond formation. Mechanical properties were assessed via tensile testing. Water contact angle, swelling ratio, cytotoxicity, and antibacterial activity were examined to evaluate biological performance.
Results: FTIR analysis confirmed new covalent and hydrogen bonding interactions leading to a stable crosslinked structure. Modified films exhibited a Young’s modulus of 1.5–2 MPa, tensile strength of 2 MPa, and a water contact angle of 45°, indicating enhanced mechanical strength and moderate hydrophilicity. The water absorption capacity reached 733%, and cell viability remained within 85–90% at the optimized glutaraldehyde concentration, confirming good biocompatibility. However, no significant antibacterial activity was observed.
Conclusion: The incorporation of chitosan and dual crosslinking with glutaraldehyde and tannic acid significantly enhanced the mechanical, wetting, and biocompatibility properties of hyaluronic acid-based films, making them promising candidates for wound dressing applications. Further enhancement of antibacterial activity, possibly by incorporating antibacterial nanoparticles, is recommended for broader clinical use.

کلیدواژه‌ها [English]

  • Hyaluronic acid
  • Chitosan
  • Chemical modification
  • Polymeric films
  • Wound dressing

مراجع

  1. Jin M, Shi J, Zhu W, Yao H, Wang DA. Polysaccharide-based biomaterials in tissue engineering: a review. Tissue Eng Part B Rev. 2021;27(6):604-26. https://doi.org/10.1089/ten.teb.2020.0208
  2. Petrila LM, Bucatariu F, Mihai M, Teodosiu C. Polyelectrolyte multilayers: An overview on fabrication, properties, and biomedical and environmental applications. Materials. 2021;14(15): 4152. https://doi.org/10.3390/ma14154152
  3. Wang CG, Surat'man NE, Chang JJ, Ong ZL, Li B, Fan X, Loh XJ, Li Z. Polyelectrolyte hydrogels for tissue engineering and regenerative medicine. Chemistry–An Asian J. 2022;17(18):e202200604. https://doi.org/10.1002/asia.202200604
  4. Sivakumar PM, Yetisgin AA, Demir E, Sahin SB, Cetinel S. Polysaccharide-bioceramic composites for bone tissue engineering: A review. Int J Biol Macromol. 2023;126:237. https://doi.org/10.1016/j.ijbiomac.2023.01.174
  5. Kastania G, Campbell J, Mitford J, Volodkin D. Polyelectrolyte multilayer capsule (PEMC)-based scaffolds for tissue engineering. Micromachines. 2020;11(9):797. https://doi.org/10.3390/mi11090797
  6. Niziołek K, Słota D, Sobczak-Kupiec A. Polysaccharide-based composite systems in bone tissue engineering: A review. Materials. 2024;17(17): 4220. https://doi.org/10.3390/ma17174220
  7. Lin Y, Wang X, Liu Q, Fang Y. Preparation and application of chitosan-based polyelectrolyte complex materials: An overview. Paper & Biomaterials. 2022; 7(4). https://doi.org/10.53594/pb.2022.7.4.014
  8. Fourie J, Taute F, du Preez L, De Beer D. Chitosan composite biomaterials for bone tissue engineering—a review. Regen Eng Transl Med. 2022;1-21. https://doi.org/10.1007/s40810-022-00141-1
  9. Zheng Z, Patel M, Patel R. Hyaluronic acid-based materials for bone regeneration: A review. React Funct Polym. 2022;171:105151. https://doi.org/10.1016/j.reactfunctpolym.2022.105151
  10. Savencu I, Iurian S, Porfire A, Bogdan C, Tomuță I. Review of advances in polymeric wound dressing films. React Funct Polym. 2021;168:105059. https://doi.org/10.1016/j.reactfunctpolym.2021.105059
  11. Gonçalves MM, Carneiro J, Justus B, Espinoza JT, Budel JM, Farago PV, Paula JP. Preparation and characterization of a novel antimicrobial film dressing for wound healing application. Braz J Pharm Sci. 2021;56:e18784. https://doi.org/10.1590/s2175-97902021000318784
  12. da Silva TN, Cardoso SA, da Silva FF, de Carvalho Patricio BF, Gonçalves RP, Weissmuller G, El-cheikh MC, Carneiro K, Barradas TN. Chitosan-based films filled with nanoencapsulated essential oil: Physical-chemical characterization and enhanced wound healing activity. Int J Biol Macromol. 2024;261: 129049. https://doi.org/10.1016/j.ijbiomac.2023.12.099
  13. Kuddushi M, Shah AA, Ayranci C, Zhang X. Recent advances in novel materials and techniques for developing transparent wound dressings. J Mater Chem B. 2023;11(27):6201-24. https://doi.org/10.1039/d3tb00547b
  14. Borbolla-Jiménez FV, Peña-Corona SI, Farah SJ, Jiménez-Valdés MT, Pineda-Pérez E, Romero-Montero A, Del Prado-Audelo ML, Bernal-Chávez SA, Magaña JJ, Leyva-Gómez G. Films for wound healing fabricated using a solvent casting technique. Pharmaceutics. 2023;15(7):1914. https://doi.org/10.3390/pharmaceutics15071914
  15. Saraiva MM, Campelo MD, Camara Neto JF, Lima AB, Silva GD, Dias AT, Ricardo NM, Kaplan DL, Ribeiro ME. Alginate/polyvinyl alcohol films for wound healing: Advantages and challenges. J Biomed Mater Res Part B Appl Biomater. 2023;111(1):220-33. https://doi.org/10.1002/jbm.b.34993
  16. Koshy JT, Vasudevan D, Sangeetha D, Prabu AA. Biopolymer based multifunctional films loaded with anthocyanin rich floral extract and ZnO nanoparticles for smart packaging and wound healing applications. Polymers. 2023;15(10):2372. https://doi.org/10.3390/polym15102372
  17. Savencu I, Iurian S, Porfire A, Bogdan C, Tomuță I. Review of advances in polymeric wound dressing films. React Funct Polym. 2021;168:105059. https://doi.org/10.1016/j.reactfunctpolym.2021.105059
  18. Moholkar DN, Sadalage PS, Peixoto D, Paiva-Santos AC, Pawar KD. Recent advances in biopolymer-based formulations for wound healing applications. Eur Polym J. 2021;160:110784. https://doi.org/10.1016/j.eurpolymj.2021.110784
  19. de Souza RF, de Souza FC, Bierhalz AC, Pires AL, Moraes ÂM. Biopolymer-based films and membranes as wound dressings. In: Biopolymer Membranes and Films. Elsevier. 2020;165-94. https://doi.org/10.1016/B978-0-12-817227-2.00009-6
  20. MohammadKarimi S, Ershad-Langroudi A, Alizadegan Surface analysis and water contact angle of modified natural biopolymers. In: Handbook of Natural Polymers, Volume 2. Elsevier. 2024;473-500. https://doi.org/10.1016/B978-0-12-819471-7.00022-0
  21. Kumar A, Mishra RK, Verma K, Aldosari SM, Maity CK, Verma S, Patel R, Thakur VK. A comprehensive review of various biopolymer composites and their applications: from biocompatibility to self-healing. Mater Today Sustain. 2023;23:100431. https://doi.org/10.1016/j.mtsust.2023.100431
  22. Priya S, Choudhari M, Tomar Y, Desai VM, Innani S, Dubey SK, Singhvi G. Exploring polysaccharide-based bio-adhesive topical film as a potential platform for wound dressing application: A review. Carbohydr Polym. 2023;121:121655. https://doi.org/10.1016/j.carbpol.2023.121655
  23. Kozłowska J, Skopińska-Wiśniewska J, Kaczmarek-Szczepańska B, Grabska-Zielińska S, Makurat-Kasprolewicz B, Michno A, Ronowska A, Wekwejt M. Gelatin and gelatin/starch-based films modified with sorbitol for wound healing. J Mech Behav Biomed Mater. 2023;148:106205. https://doi.org/10.1016/j.jmbbm.2023.106205
  24. Kumar M, Mahmood S, Chopra S, Bhatia A. Biopolymer based nanoparticles and their therapeutic potential in wound healing–A review. Int J Biol Macromol. 2024;131:131335. https://doi.org/10.1016/j.ijbiomac.2024.01.070
  25. Gobi R, Ravichandiran P, Babu RS, Yoo DJ. Biopolymer and synthetic polymer-based nanocomposites in wound dressing applications: a review. Polymers. 2021;13(12):1962. https://doi.org/10.3390/polym13121962
  26. Savencu I, Iurian S, Porfire A, Bogdan C, Tomuță I. Review of advances in polymeric wound dressing films. React Funct Polym. 2021;168:105059. https://doi.org/10.1016/j.reactfunctpolym.2021.105059
  27. Abourehab MA, Rajendran RR, Singh A, Pramanik S, Shrivastav P, Ansari MJ, Manne R, Amaral LS, Deepak A. Alginate as a promising biopolymer in drug delivery and wound healing: A review of the state-of-the-art. Int J Mol Sci. 2022;23(16):9035. https://doi.org/10.3390/ijms23169035
  28. Alkhursani SA, Ghobashy MM, Al-Gahtany SA, Meganid AS, Abd El-Halim SM, Ahmad Z, Khan FS, Atia GA, Cavalu S. Application of nano-inspired scaffolds-based biopolymer hydrogel for bone and periodontal tissue regeneration. Polymers. 2022;14 (18):3791. https://doi.org/10.3390/polym14183791
  29. Chen Y, Song H, Wu M, Lu Y, Guan X. Application of protein-polysaccharide complex system in the delivery of active ingredients. Prog Chem. 2022;34 (10):2267. https://doi.org/10.53560/pc.2022.34.10.2267
  30. Bai Q, Gao Q, Hu F, Zheng C, Chen W, Sun N, Liu J, Zhang Y, Wu X, Lu T. Chitosan and hyaluronic-based hydrogels could promote the infected wound healing. Int J Biol Macromol. 2023;232:123271. https://doi.org/10.1016/j.ijbiomac.2023.03.045
  31. Alsaikhan F, Farhood B. Recent advances on chitosan/hyaluronic acid-based stimuli-responsive hydrogels and composites for cancer treatment: A comprehensive review. Int J Biol Macromol. 2024; 135:135893. https://doi.org/10.1016/j.ijbiomac.2024.01.106
  32. Shariatinia Z, Jalali AM. Chitosan-based hydrogels: Preparation, properties and applications. Int J Biol Macromol. 2018;115:194-220. https://doi.org/10.1016/j.ijbiomac.2018.03.103
  33. Kapusta O, Jarosz A, Stadnik K, Giannakoudakis DA, Barczyński B, Barczak M. Antimicrobial natural hydrogels in biomedicine: Properties, applications, and challenges—A concise review. Int J Mol Sci. 2023;24(3):2191. https://doi.org/10.3390/ijms24032191
  34. Luo Y, Tan J, Zhou Y, Guo Y, Liao X, He L, Li D, Li X, Liu Y. From crosslinking strategies to biomedical applications of hyaluronic acid-based hydrogels: A review. Int J Biol Macromol. 2023;231:123308. https://doi.org/10.1016/j.ijbiomac.2023.03.111
  35. Wekwejt M, Małek M, Ronowska A, Michno A, Pałubicka A, Zasada L, Klimek A, Kaczmarek-Szczepańska B. Hyaluronic acid/tannic acid films for wound healing application. Int J Biol Macromol. 2024;254:128101. https://doi.org/10.1016/j.ijbiomac.2023.12.157
  36. Zhu L, Ouyang F, Fu X, Wang Y, Li T, Wen M, Zha G, Yang X. Tannic acid modified keratin/sodium alginate/carboxymethyl chitosan biocomposite hydrogels with good mechanical properties and swelling behavior. Sci Rep. 2024;14(1):12864. https://doi.org/10.1038/s41598-024-36114-5
  37. Lewandowska K, Sionkowska A, Grabska S, Michalska M. Characterisation of chitosan/hyaluronic acid blend films modified by collagen. Prog Chem Appl Chitin Deriv. 2017;22:125-34. https://doi.org/10.1515/pca-2017-0012
  38. Sionkowska A, Michalska-Sionkowska M, Walczak M. Preparation and characterization of collagen/ hyaluronic acid/chitosan film crosslinked with dialdehyde starch. Int J Biol Macromol. 2020;149: 290-5. https://doi.org/10.1016/j.ijbiomac.2020.02.145
  39. Sionkowska A, Grabska S, Lewandowska K, Michalska M. The miscibility of collagen/hyaluronic acid/chitosan blends investigated in dilute solutions and solids. J Mol Liq. 2016;220:726-30. https://doi.org/10.1016/j.molliq.2016.05.091
  40. Pavoni JM, dos Santos NZ, May IC, Pollo LD, Tessaro IC. Impact of acid type and glutaraldehyde crosslinking in the physicochemical and mechanical properties and biodegradability of chitosan films. Polym Bull. 2021;78: 981-1000. https://doi.org/10.1007/s00289-020-03394-0
  41. Wardhono EY, Pinem MP, Susilo S, Siom BJ, Sudrajad A, Pramono A, Meliana Y, Guénin E. Modification of physio-mechanical properties of chitosan-based films via physical treatment approach. Polymers. 2022;14(23):5216. https://doi.org/10.3390/polym14235216
  42. Baldwin A, Booth BW. Biomedical applications of tannic acid. J Biomater Appl. 2022;36(8):1503-23. https://doi.org/10.1177/08853282221077914
  43. Maiz-Fernández S, Pérez-Álvarez L, Silván U, Vilas-Vilela JL, Lanceros-Méndez S. Dynamic and self-healable chitosan/hyaluronic acid-based in situ-forming hydrogels. Gels. 2022;8(8):477. https://doi.org/10.3390/gels8080477
  44. Alkabli J. Recent advances in the development of chitosan/hyaluronic acid-based hybrid materials for skin protection, regeneration, and healing: A review. Int J Biol Macromol. 2024;135357. https://doi.org/10.1016/j.ijbiomac.2024.09.006
  45. Ding YW, Wang ZY, Ren ZW, Zhang XW, Wei DX. Advances in modified hyaluronic acid-based hydrogels for skin wound healing. Biomater Sci. 2022;10(13):3393-409. https://doi.org/10.1039/d2bm00383d
  46. Wang Y, Wang Z, Lu W, Hu Y. Review on chitosan-based antibacterial hydrogels: preparation, mechanisms, and applications. Int J Biol Macromol. 2024;255:128080. https://doi.org/10.1016/j.ijbiomac.2023.12.033
  47. Lv S, Zhang S, Zuo J, Liang S, Yang J, Wang J, Wei D. Progress in preparation and properties of chitosan-based hydrogels. Int J Biol Macromol. 2023;242:124915. https://doi.org/10.1016/j.ijbiomac.2023.04.045
  48. Grabska-Zielińska S. Cross-linking agents in three-component materials dedicated to biomedical applications: A review. Polymers. 2024;16(18):2679. https://doi.org/10.3390/polym16182679
  49. Yan M, An X, Duan S, et al. A comparative study on cross-linking of fibrillar gel prepared by tilapia collagen and hyaluronic acid with EDC/NHS and genipin. Int J Biol Macromol. 2022;213:639-50. https://doi.org/10.1016/j.ijbiomac.2022.06.081
  50. Drozdova M, Vodyakova M, Tolstova T, et al. Composite hydrogels based on cross-linked chitosan and low molecular weight hyaluronic acid for tissue engineering. Polymers. 2023;15(10):2371. https://doi.org/10.3390/polym15102371
  51. Grabska-Zielińska S. Cross-linking agents in three-component materials dedicated to biomedical applications: A review. Polymers. 2024;16(18):2679. https://doi.org/10.3390/polym16182679

 

 

مواد پیشرفته در مهندسی
دوره 44، شماره 4
(شماره پیاپی 51)
1404
صفحه 55-73

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