پانسمان نوین الیافی پلی‌کاپرولاکتون/ژلاتین حاوی ویتامین C و داروی آنتی‌باکتریال جهت درمان زخم‌های پوستی

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه مهندسی بافت، دانشگاه آزاد اسلامی واحد نجف آباد

2 2- گروه بیومتریال، نانو تکنولوژی و مهندسی بافت، دانشکده فناوری‌های نوین علوم پزشکی، دانشگاه علوم پزشکی اصفهان 3- مرکز تحقیقات بیوسنسور، دانشگاه علوم پزشکی اصفهان

3 گروه بیوشیمی، دانشگاه آزاد اسلامی واحد نجف آباد

چکیده

زخم‌های پوستی ناشی از سوختگی، آسیب‌های فیزیکی و بیماری‌هایی مانند دیابت در اثر عفونت و عدم رگ‌زایی مناسب می‌توانند منجر به آسیب‌های قطع عضو و حتی مرگ و میر افراد شوند. در این تحقیق، ترکیب پلیمر‌های پلی‌کاپرولاکتون و ژلاتین جهت الکتروریسی تهیه شده و داروی سیپروفلوکساسین و ویتامین C به‌صورت مجزا بارگذاری شد. ابتدا جهت بررسی ویژگی‌های مورفولوژی از میکروسکوپ الکترونی روبشی استفاده شد و سپس ارزیابی زاویه تماس، میزان تورم، نرخ تخریب و استحکام کششی صورت گرفت. همچنین، پاسخ سلول‌های فیبروبلاست از نظر تکثیر و چسبندگی سلولی بررسی شد. نتایج نشان داد که الیاف زخم پوش فاقد و حاوی دارو یکنواخت بوده و به‌ترتیب دارای قطری برابر با 244±1039/96 و 406±1403/72 نانومتر است. همچنین پانسمان حاوی و فاقد داروها محدوده وسیعی از قابلیت تورم و ماندگاری در بازه زمانی 35 روزه را نشان داد. خواص مکانیکی نمونه‌ها نیز نشان داد، با اضافه شدن داروی سیپروفلوکساسین و ویتامین C و تغییرات موفولوژی ناشی از آن، می‌توان استحکام کششی را تا 3/5 برابر افزایش داد. در بررسی سلول سازگاری زخم پوش مورد نظر مشاهده شد که وجود دارو در سامانه هیچ‌گونه اثر نامطلوبی بر سلول‌ها نداشته و تکثیر، رشد و چسبندگی سلول‌ فیبروبلاست پوستی بر روی سطح نمونه مشاهده ‌شد. ضمناً ترکیب پلیمر‌های ژلاتین و پلی‌کاپرولاکتون بدون نیاز به اتصال عرضی می‌تواند روند تخریب مناسب و رهایش مناسب برای دارو‌های بارگذاری شده را مهیا کند در‌حالی که خواص مکانیکی و انعطاف‌پذیری نیز در حد مطلوب حفظ شود. 

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

A Novel Fibrous Polycaprolactone/Gelatin Wound Dressing Containing Vitamin C and Antibacterial Drug For Wound Healing

نویسندگان [English]

  • Z. Ashuri 1
  • M. Tayibi 1
  • A. Zargar Kharazi 2
  • E. Pourazizi 3
1 Department of Tissue Engineering, Islamic Azad University, Najaf Abad branch,Najafabad, Iran
2 2- Department of Biomaterials, Nanotechnology and Tissue Engineering, Faculty of Modern Medical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran 3- Biosensor Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Biochemistry, Islamic Azad University, Najaf Abad branch, Najafabad, Iran
چکیده [English]

Skin wounds caused by burns, physical injuries, and diseases such as diabetes can lead to amputation and even death of people due to infection and lack of proper angiogenesis. In this research, a wound dressing was made using the electrospinning method from a blend of poly-caprolactone and gelatin polymers which Ciprofloxacin and Vitamin C were loaded in the polymers separately. The morphology of the structure was observed by scanning electron microscope followed by evaluation of hydrophilicity, swelling, degradation rate, tensile strength, and drug release pattern. Fibroblast cell response was also considered using cytotoxicity test method. Results showed that the wound dressing fibers without drugs and containing drugs were uniform with a diameter of 1039.246 ± 96 and 1403± 406 nm, respectively. The wound dressing showed a suitable wide range of swelling ability and durability within 35 days. The tensile strength increased up to 3.5times by addition of ciprofloxacin and vitamin C due to the morphological changes. The presence of drugs in the system did not indicate any adverse effect on the cell's viability, and suitable proliferation and  adhesion of skin fibroblast cells were observed on the surface of the sample.  In addition,  a combination  of gelatin and polycaprolactone polymers could provide an appropriate degradation rate and release pattern without any cross-linking process, while preserving the mechanical properties and flexibility.

کلیدواژه‌ها [English]

  • Gelatin
  • Poly-caprolactone
  • Wound dressing
  • Drug release
  • Ascorbic acid
  • Ciprofloxacin
  1. Shevchenko R V, James SL, James SE. A review of tissue-engineered skin bioconstructs available for skin reconstruction. J R Soc Interface. 2010; 7(43):229–58. https://doi.org/10.1098/rsif.2009.0403
  2. Yu R, Zhang H, Guo B. Conductive biomaterials as bioactive wound dressing for wound healing and skin tissue engineering. Nano-micro Lett. 2022;14:1–46. https://doi.org/10.1007/s40820-021-00751-y
  3. Groeber F, Holeiter M, Hampel M, Hinderer S, Schenke-Layland K. Skin tissue engineering—in vivo and in vitro applications. Adv Drug Deliv Rev. 2011; 63(4–5):352–66. https://doi.org/10.1016/j.addr. 2011.01.005
  4. Rieger KA, Birch NP, Schiffman JD. Designing electrospun nanofiber mats to promote wound healing–a review. J Mater Chem B. 2013;1(36): 4531–41. https://doi.org/10.1039/C3TB20795A
  5. Siddiqui N, Asawa S, Birru B, Baadhe R, Rao S. PCL-based composite scaffold matrices for tissue engineering applications. Mol Biotechnol. 2018;60 (7): 506–32. http://doi.org/10.1007/s12033-018-0084-5
  6. Rai R, Tallawi M, Grigore A, Boccaccini AR. Synthesis, properties and biomedical applications of poly (glycerol sebacate)(PGS): a review. Prog Polym Sci. 2012; 37(8): 1051–78. https://doi.org/10.1016/j. progpolymsci.2012.02.001
  7. Powell HM, Boyce ST. Fiber density of electrospun gelatin scaffolds regulates morphogenesis of dermal-epidermal skin substitutes. J Biomed Mater Res - Part A. 2008;84(4):1078–86. https://doi.org/10.1002/jbm. a.31498
  8. Marchesan S, Qu Y, Waddington LJ, Easton CD, Glattauer V, Lithgow TJ, et al. Self-assembly of ciprofloxacin and a tripeptide into an antimicrobial nanostructured hydrogel. Biomaterials. 2013;34(14): 3678–87. https://doi.org/10.1016/j.biomaterials.2013. 01.096
  9. Heydari P, Varshosaz J, Zargar Kharazi A, Karbasi S. Preparation and evaluation of poly glycerol sebacate/poly hydroxy butyrate core‐shell electrospun nanofibers with sequentially release of ciprofloxacin and simvastatin in wound dressings. Polym Adv Technol. 2018. https://doi.org/10.1002/pat.4286
  10. Lu KW, Khachemoune A. Skin substitutes for the management of mohs micrographic surgery wounds: a systematic review. Arch Dermatol Res. 2023;315 (1): 17–31. http:/doi.org/10.1007/s00403-022-02327-1
  11. Daher GS, Choi KY, Wells JW, Goyal N. A systematic review of oral nutritional supplement and wound healing. Ann Otol Rhinol Laryngol. 2022;131 (12): 1358–68. https://doi.org/10.1177/00034894211069437
  12. Bechara N, Flood VM, Gunton JE. A systematic review on the role of vitamin C in tissue healing. Antioxidants. 2022;11(8):1605. https://doi.org/10.3390/antiox11081605
  13. Voss GT, Gularte MS, Vogt AG, Giongo JL, Vaucher RA, Echenique JVZ, et al. Polysaccharide-based film loaded with vitamin C and propolis: A promising device to accelerate diabetic wound healing. Int J Pharm. 2018 Dec;552(1–2):340–51. https://doi.org/10.1016/j.ijpharm.2018.10.009
  14. Moores J. Vitamin C: a wound healing perspective. Br J Community Nurs. 2013;18(Sup12):S6–11. http://doi .org/10.12968/bjcn.2013.18.sup12.s6
  15. Mohammed BM, Fisher BJ, Kraskauskas D, Ward S, Wayne JS, Brophy DF, et al. Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J. 2016;13(4):572–84. https://doi.org/10.1111/ iwj.12484
  16. Andreu V, Mendoza G, Arruebo M, Irusta S. Smart dressings based on nanostructured fibers containing natural origin antimicrobial, anti-inflammatory, and regenerative compounds. Materials (Basel). 2015;8(8): 5154–93. https://doi.org/10.3390/ma8085154
  17. Rancan F, Contardi M, Jurisch J, Blume-Peytavi U, Vogt A, Bayer IS, et al. Evaluation of drug delivery and efficacy of ciprofloxacin-loaded povidone foils and nanofiber mats in a wound-infection model based on ex vivo human skin. Pharmaceutics. 2019;11(10): 527. https://doi.org/10.3390/pharmaceutics11100527
  18. George L, Bavya MC, Rohan KV, Srivastava R. A therapeutic polyelectrolyte–vitamin C nanoparticulate system in polyvinyl alcohol–alginate hydrogel: An approach to treat skin and soft tissue infections caused by Staphylococcus aureus. Colloids Surf B Biointerfaces. 2017;160:315–24. https://doi.org/10. 1016/j.colsurfb.2017.09.030
  19. Shin YC, Shin D, Lee EJ, Lee JH, Kim JE, Song SH, et al. Hyaluronic acid/PLGA core/shell fiber matrices loaded with EGCG beneficial to diabetic wound healing. Adv Healthc Mater. 2016;5(23):3035–45. https://doi.org/10.1016/j.colsurfb.2017.09.030
  20. Liu S, Yu J, Li H, Wang K, Wu G, Wang B, et al. Controllable drug release behavior of polylactic acid (PLA) surgical suture coating with ciprofloxacin (CPFX)—polycaprolactone (PCL)/polyglycolide (PGA). Polymers (Basel). 2020;12(2):288. https://doi.org/10. 3390/polym12020288
  21. Kearns V, MacIntosh AC, Crawford A, Hatton P V. Silk-based biomaterials for tissue engineering. Top tissue Eng. 2008;4:1–19.
  22. Karizmeh MS, Poursamar SA, Kefayat A, Farahbakhsh Z, Rafienia M. An in vitro and in vivo study of PCL/chitosan electrospun mat on polyurethane/propolis foam as a bilayer wound dressing. Biomater Adv. 2022; 135:112667. https://doi.org/10.1016/j.msec.2022.112667
  23. Kharaziha M, Nikkhah M, Shin S ryon, Annabi N. Biomaterials PGS : Gelatin nano fi brous scaffolds with tunable mechanical and structural properties for engineering cardiac tissues. 2013;34. https://doi.org/ 10.1016/j.biomaterials.2013.04.045
  24. George L, Bavya MC, Rohan KV, Srivastava R. A therapeutic polyelectrolyte–vitamin C nanoparticulate system in polyvinyl alcohol–alginate hydrogel: An approach to treat skin and soft tissue infections caused by Staphylococcus aureus. Colloids Surf B Biointerfaces 2017; 160: 315–24. https://doi.org/10. 1016/j.colsurfb.2017.09.030
  25. Vogt L, Rivera LR, Liverani L, Piegat A, El Fray M, Boccaccini AR. Poly (ε-caprolactone)/poly (glycerol sebacate) electrospun scaffolds for cardiac tissue engineering using benign solvents. Mater Sci Eng C. 2019;103:109712. https://doi.org/10.1016/j.msec.2019. 04.091
  26. Depan D, Misra RDK. Hybrid nanoscale architecture of wound dressing with super hydrophilic, antimicrobial, and ultralow fouling attributes. J Biomed Nanotechnol. 2015; 11(2): 306–18. https://doi.org/10.1016/j.msec.2019. 04.091
  27. Wang W, Caetano G, Ambler WS, Blaker JJ, Frade MA, Mandal P, et al. Enhancing the hydrophilicity and cell attachment of 3D printed PCL/graphene scaffolds for bone tissue engineering. Materials (Basel). 2016; 9(12): 992. https://doi.org/10.3390/ma 9120992
  28. Chen H, Lan G, Ran L, Xiao Y, Yu K, Lu B, et al. A novel wound dressing based on a Konjac glucomannan/silver nanoparticle composite sponge effectively kills bacteria and accelerates wound healing. Carbohydr Polym. 2018;183:70–80. https:// doi.org/10.3390/ma9120992
  29. Ye P, Wei S, Luo C, Wang Q, Li A, Wei F. Long-term effect against methicillin-resistant staphylococcus aureus of emodin released from coaxial electrospinning nanofiber membranes with a biphasic profile. Biomolecules. 2020;10(3):362. https://doi.org/10.3390/ biom10030362
  30. Elsayed RE, Madkour TM, Azzam RA. Tailored-design of electrospun nanofiber cellulose acetate/poly(lactic acid) dressing mats loaded with a newly synthesized sulfonamide analog exhibiting superior wound healing. Int J Biol Macromol. 2020 Dec;164:1984–99. https://doi.org/10.1016/j.ijbiomac. 2020.07.316
  31. Salehi M, Niyakan M, Ehterami A, Haghi-Daredeh S, Nazarnezhad S, Abbaszadeh-Goudarzi G, et al. Porous electrospun poly(ε-caprolactone)/gelatin nanofibrous mat containing cinnamon for wound healing application: in vitro and in vivo study. Biomed Eng Lett. 2020 Feb 18;10(1):149–61. http://doi.org/10.1007/s13534-019-00138-4
  32. El Fawal G, Hong H, Mo X, Wang H. Fabrication of scaffold based on gelatin and polycaprolactone (PCL) for wound dressing application. J Drug Deliv Sci Technol. 2021;63:102501. https://doi.org/10.1016/j.jddst. 2021.102501
  33. Gil-Castell O, Badia JD, Ontoria-Oviedo I, Castellano D, Sepúlveda P, Ribes-Greus A. Polycaprolactone/gelatin-based scaffolds with tailored performance: in vitro and in vivo validation. Mater Sci Eng C. 2020;107:110296. https://doi.org/10. 1016/ j.msec.2019.110296
  34. Figueira DR, Miguel SP, de Sa KD, Correia IJ. Production and characterization of polycaprolactone-hyaluronic acid/chitosan-zein electrospun bilayer nanofibrous membrane for tissue regeneration. Int J Biol Macromol. 2016;93:1100–10. https://doi.org/10. 1016/j.ijbiomac.2016.09.080
  35. Tayebi M, Parham S, Abbastabbar Ahangar H, Zargar Kharazi A. Preparation and evaluation of bioactive bilayer composite membrane PHB/β‐TCP with ciprofloxacin and vitamin D3 delivery for regenerative damaged tissue in periodontal disease. J Appl Polym Sci. 2022;139(3):51507. https://doi.org/10.1002/app.51507
  36. Kong Y, Tang X, Zhao Y, Chen X, Yao K, Zhang L, et al. Degradable tough chitosan dressing for skin wound recovery. Nanotechnol Rev. 2020;9(1):1576–85. https://doi.org/10.1515/ntrev-2020-0105
  37. Shirazaki P, Varshosaz J, Kharazi AZ. Electrospun Gelatin/poly(Glycerol Sebacate) Membrane with Controlled Release of Antibiotics for Wound Dressing. Adv Biomed Res [Internet]. 2017 Aug 28;6:105. http://doi:10.4103/abr.abr_197_16
  38. Moreno L, Wang C, Lamaka S V, Zheludkevich ML, Rodríguez-Hernández J, Arrabal R, et al. Ciprofloxacin Release and Corrosion Behaviour of a Hybrid PEO/PCL Coating on Mg3Zn0.4Ca Alloy. Vol. 14, J Funct Biomater. 2023. https://doi.org/ 10.3390/jfb14020065
  39. Vivcharenko V, Wojcik M, Przekora A. Cellular response to vitamin C-enriched chitosan/agarose film with potential application as artificial skin substitute for chronic wound treatment. Cells. 2020;9(5):1185. http://doi/ 10.3390/cells9051185
  40. Khaloo Kermani P, Zargar Kharazi A. A promising antibacterial wound dressing made of electrospun poly (glycerol sebacate)(PGS)/gelatin with local delivery of ascorbic acid and pantothenic acid. J Polym Environ. 2023;31(6):2504–18. http://doi.org/ 10.1007/s10924-022-02715-8

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