Abstract
In the presented study, thymol-containing wound dressing films were prepared in the presence of polysaccharide gellan gum, carboxymethyl cellulose and hyaluronic acid polymers by solvent casting technique. The structure of the obtained films was characterized by Fourier transform infrared attenuated total reflection spectroscopy and scanning electron microscopy analysis. The swelling ratios of the thymol-containing films were adequate to supply a moist environment (∼ 829%, for 24 h measurement) and underwent a hydrolytic degradation (∼ 55%, for 21 days measurement). The water vapor transmission rates were moderate for sufficient moisture (∼ 2376 g/m2/day). According to the findings, the addition of thymol to the polymeric films increased the elongation at break value. The cumulative release amounts of thymol were increased from 4.42 ± 0.40 mg thymol/g film to 6.25 ± 0.39 mg thymol/g film by increasing thymol concentration in the formulation. In vitro biocompatibility and wound healing tests were also performed against the L929 fibroblast cell line. The findings demonstrated that the migration and proliferation of L929 fibroblast cells were greatly improved by the formulation of non-toxic polysaccharide-based 5% (w) thymol-containing film (GCH-5), and therefore it could be a potential wound dressing material for the clinical use.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Abdallah EM, Morsi MA, Asnag GM, Tarabiah AE (2022) Structural, optical, thermal, and dielectric properties of carboxymethyl cellulose/sodium alginate blend/lithium titanium oxide nanoparticles: biocomposites for lithium-ion batteries applications. Int J Energy Res 46:10741–10757. https://doi.org/10.1016/j.jpcs.2018.10.009
Ahmady AR, Razmjooee K, Saber-Samandari S, Toghraie D (2022) Fabrication of chitosan-gelatin films incorporated with thymol-loaded alginate microparticles for controlled drug delivery, antibacterial activity and wound healing: in-vitro and in-vivo studies. Int J Biol Macromol 223:567–582. https://doi.org/10.1016/j.ijbiomac.2022.10.249
Amanat S, Taymouri S, Varshosaz J, Minaiyan M, Talebi A (2020) Carboxymethyl cellulose-based wafer enriched with resveratrol-loaded nanoparticles for enhanced wound healing. Drug Deliv Transl Res 10:1241–1254. https://doi.org/10.1007/s13346-020-00711-w
Aycan D, Selmi B, Kelel E, Yildirim T, Alemdar N (2019) Conductive polymeric film loaded with ibuprofen as a wound dressing material. Eur Polym J 121:109308. https://doi.org/10.1016/j.eurpolymj.2019.109308
Bankoti K, Rameshbabu AP, Datta S, Maity PP, Goswami P, Datta P, Ghosh SK, Mitra A, Dhara S (2017) Accelerated healing of full thickness dermal wounds by macroporous waterborne polyurethane-chitosan hydrogel scaffolds. Mater Sci Eng C 81:133–143. https://doi.org/10.1016/j.msec.2017.07.018
Bayer IS (2020) Hyaluronic acid and controlled release: a review. Molecules 25(11):2649. https://doi.org/10.3390/molecules25112649
Buyana B, Aderibigbe BA, Nditheh DT, Fonkui YT, Kumar P (2020) Alginate-pluronic topical gels loaded with thymol, norfloxacin and ZnO nanoparticels as potential wound dressings. J Drug Deliv Sci Technol 60:101960. https://doi.org/10.1016/j.jddst.2020.101960
Chen Y, Qiu Y, Chen W, Wei Q (2020a) Electrospun thymol-loaded porous cellulose acetate fibers with potential biomedical applications. Mater Sci Eng C https://doi.org/10.1016/j.msec.2019.110536
Chen Y, Mensah A, Wang Q, Li D, Qiu Y, Wei Q (2020b) Hierarchical porous nanofibers containing thymol/beta-cyclodextrin: physico-chemical characterization and potential biomedical applications. Mater Sci Eng C https://doi.org/10.1016/j.msec.2020.111155
Du J, Fu F, Shi X, Yin Z (2015) Controlled release of a model protein drug ovalbumin ftom thiolated hyaluronic acid matrix. J Drug Deliv Sci Technol 30:74–81. https://doi.org/10.1016/j.jddst.2015.09.015
Evranos B, Aycan D, Alemdar N (2019) Production of ciprofloxacin loaded chitosan/gelatin/bone ash wound dressing with improved mechanical properties. Carbohydr Polym 222:115007. https://doi.org/10.1016/j.carbpol.2019.115007
Farshi P, Salarian R, Rabiee M, Alizadeh S, Gholipourmalekabadi SA, Rabiee N (2022) Design, preparation, and characterization of silk fibroin/carboxymethyl cellulose wound dressing for skin tissue regeneration applications. Polym Eng Sci 62(9):2741–2749. https://doi.org/10.1002/pen.26057
Gaspar-Pintililescu A, Stanciuc AM, Craciunescu O (2019) Natural composite dressings based on collagen, gelatin and plant bioactive compounds for wound healing: a review. Int J Biol Macromol 138:854–865. https://doi.org/10.1016/j.ijbiomac.2019.07.155
Hajian M, Mahmoodi M, Imani R (2017) In vitro assessment of poly (vinyl alcohol) film incorporating aloe vera for potential application as a wound dressing. J Macromol Sci Phys 56:435–450. https://doi.org/10.1080/00222348.2017.1330183
Jiji S, Udhayakumar S, Rose C, Muralidharan C, Kadirvelu K (2019) Thymol enriched bacterial cellulose hydrogel as effective material for third degree burn wound repair. Int J Biol Macromol 122:452–460. https://doi.org/10.1016/j.ijbiomac.2018.10.192
Kanikireddy V, Varaprasad K, Jayaramudu T, Karthikeyan C, Sadiku R (2020) Carboxymethyl cellulose-based materials for infection control and wound healing: a review. Int J Biol Macromol 164:973–975. https://doi.org/10.1016/j.ijbiomac.2020.07.160
Karthika JS, Vishalakshi B (2015) Novel stimuli responsive gellan gum-graft-poly(DMAEMA) hydrogel as adsorbent for anionic dye. Int J Biol Macromol 81:648–655. https://doi.org/10.1016/j.ijbiomac.2015.08.064
Kavoosi G, Dadfar SMM, Purfard AM (2013) Mechanical, physical, antioxidant, and antimicrobial properties of gelatin films incorporated with thymol for potential use as nano wound dressing. J Food Sci 78(2):E244–E250. https://doi.org/10.1111/1750-3841.12015
Kavoosi G, Bordbar Z, Dadfar, SM, Dadfar SMM (2017) Preparation and characterization of a novel gelatin-poly(vinyl alcohol) hydrogel film loaded with Zataria multiflora essential oil for antibacterial–antioxidant wound-dressing applications. J Appl Polym Sci 134(39): 45351. https://doi.org/10.1002/app.45351
Kocaaga B, Kurkcuoglu O, Tatlier M, Batirel S, Guner FS (2019) Low-methoxyl pectin–zeolite hydrogels controlling drug release promote in vitro wound healing. J Appl Polym Sci 136(24):47640. https://doi.org/10.1002/app.47640
Koosehgol S, Ebrahimian-Hosseinabadi M, Alizadeh M, Zamanian A (2017) Preparation and characterization of in situ chitosan/polyethylene glycol fumarate/thymol hydrogel as an effective wound dressing. Mater Sci Eng C 79:66–75. https://doi.org/10.1016/j.msec.2017.05.001
Koyyada A, Orsu P (2021) Nanofibrous scaffolds of carboxymethyl guargum potentiated with reduced graphene oxide for in vitro and in vivo wound healing applications. Int J Pharm 607:121035. https://doi.org/10.1016/j.ijpharm.2021.121035
Li S, Li L, Guo C, Qin H, Yu X (2017) A promising wound dressing material with excellent cytocompatibility and proangiogenesis action for wound healing: strontium loaded silk fibroin/sodium alginate (SF/SA) blend films. Int J Biol Macromol 104:969–978. https://doi.org/10.1016/j.ijbiomac.2017.07.020
Lin YH, Lee S, Lin FH, Wu GX, Wu CS, Kuo SM (2021) Enhancement of rotator cuff healing with farnesol-ımpregnated gellan gum/hyaluronic acid hydrogel membranes in a rabit model. Pharmaceutics 13(7):944. https://doi.org/10.3390/pharmaceutics13070944
Liu J, Ismail NA, Yusoff M, Razali MH (2022) Physicochemical properties and antibacterial activity of gellan gum ıncorporating zinc oxide/carbon nanotubes bionanocomposite film for wound healing. Bioinorg Chem Appl. https://doi.org/10.1155/2022/3158404
Mahmood H, Khan IU, Asif M, Khan RU, Asghar S, Khalid I, Khalid SH, Irfan M, Rehman F, Shahzad Y, Yousaf AM, Younus A, Niazi ZR, Asim M (2021) In vitro and in vivo evaluation of gellan gum hydrogel films: assessing the co impact of therapeutic oils and ofloxacin on wound healing. Int J Biol Macromol 166:483–495. https://doi.org/10.1016/j.ijbiomac.2020.10.206
Meng X, Lu Y, Gao Y, Cheng S, Tian F, Xiao Y, Li F (2021) Chitosan/alginate/hyaluronic acid polyelectrolyte composite sponges crosslinked with genipin for wound dressing application. Int J Biol Macromol 182:512–523. https://doi.org/10.1016/j.ijbiomac.2021.04.044
Mert H, Özkahraman B, Damar H (2020) A novel wound dressing material: pullulan grafted copolymer hydrogel via UV copolymerization and crosslinking. J Drug Deliv Sci Technol 60:101962. https://doi.org/10.1016/j.jddst.2020.101962
Michalska-Sionkowska M, Walczak M, Sionkowska A (2017) Antimicrobial activity of collagen material with thymol addition for potential applications as wound dressings. Polym Test 63:360–366. https://doi.org/10.1016/j.polymertesting.2017.08.036
Mohy Eldin MS, El-Sherif HM, Soliman EA, Elzatahry AA, Omer AM (2011) Polyacrylamide-grafted carboxymethyl cellulose: smart pH-sensitive hydrogel for protein concentration. J Appl Polym Sci 122:469–479. https://doi.org/10.1002/app.33283
Nangia A, Hung CT (1989) Design of a new hydrocolloid dressing. Burns 15:385–388. https://doi.org/10.1016/0305-4179(89)90104-6
Nikjoo D, van der Zwaan I, Brülls M, Tehler U, Frenning G (2021) Hyaluronic acid hydrogels for controlled pulmonary drug delivery: a particle engineering approach. Pharmaceutics 13:1878. https://doi.org/10.3390/pharmaceutics13111878
Özbaş Z, Özkahraman B, Bayrak G, Kılıç Süloğlu A, Perçin I, Boran F, Tamahkar E (2021) Poly(vinyl alcohol)/(hyaluronic acid-g-kappa-carrageenan) hydrogel as antibiotic-releasing wound dressing. Chem Pap 75:6591–6600. https://doi.org/10.1007/s11696-021-01824-3
Özbaş Z, Özkahraman B, Akgüner ZP, Bal-Öztürk A (2022) Evaluation of modified pectin/alginate buccal patches with enhanced mucoadhesive properties for drug release systems: in vitro and ex-vivo study. J Drug Deliv Sci Technol 67:102991. https://doi.org/10.1016/j.jddst.2021.102991
Özen N, Özbaş Z, İzbudak B, Emik S, Özkahraman B, Bal-Öztürk A (2022) Boric acid-impregnated silk fibroin/gelatin/hyaluronic acid-based films for improving the wound healing process. J Appl Polym Sci 139(9):51715. https://doi.org/10.1002/app.51715
Özkahraman B, Özbaş Z (2020) Removal of Al(III) ions using gellan gum-acrylic acid double network hydrogel. J Polym Environ 28:689–698. https://doi.org/10.1007/s10924-019-01636-3
Özkahraman B, Özbaş Z, Bayrak G, Tamahkar E, Perçin I, Kılıç-Süloğlu A, Boran F (2022a) Characterization and antibacterial activity of gelatin-gellan gum bilayer wound dressing. Int J Polym Mater Polym Biomater 71(16):1240–1251. https://doi.org/10.1080/00914037.2021.1960341
Özkahraman B, Özbaş Z, Yaşayan G, Akgüner ZP, Yarımcan F, Alarçin E, Bal-Öztürk A (2022b) Development of mucoadhesive modified kappa-carrageenan/pectin patches for controlled delivery of drug in the buccal cavity. J Biomed Mater Res B Appl Biomater 110(4):787–798. https://doi.org/10.1002/jbm.b.34958
Özkahraman B, Torkay G, Özbaş Z, Bal-Öztürk A (2023) The effect of vitamin C in the formulation of pectin/thiolated alginate buccal adhesive patches: in vitro and ex vivo evaluation. Int J Adhes Adhes 120:103276. https://doi.org/10.1016/j.ijadhadh.2022.103276
Pires ALR, de Azevedo Motta L, Dias AM, de Sousa HC, Moraes ÂM, Braga ME (2018) Towards wound dressings with improved properties: effects of poly (dimethylsiloxane) on chitosan-alginate films loaded with thymol and beta-carotene. Mater Sci Eng C 93:595–605. https://doi.org/10.1016/j.msec.2018.08.005
Queen D, Gaylor JD, Evans J, Courtney J, Reid W (1987) The preclinical evaluation of the water vapor transmission rate through burn wound dressings. Biomaterials 8:367–371. https://doi.org/10.1016/0142-9612(87)90007-X
Rahman SR, Augustine R, Zahid AA, Ahmed R, Tariq M, Hasan A (2019) Reduced graphene oxide incorporated GelMA hydrogel promotes angiogenesis for wound healing applications. Int J Nanomed 14:9603–9617. https://doi.org/10.2147/IJN.S367492
Rojas-Grau MA, Avena-Bustillos RJ, Olsen C, Friedman M, Henika PR, Martin-Belloso O, Pan Z, McHugh TH (2007) Effects of plant essential oils and oil compounds on mechanical, barrier and antimicrobial properties of alginate–apple puree edible films. J Food Eng 81:634–641. https://doi.org/10.1016/j.jfoodeng.2007.01.007
Sala FD, Longobardo G, Fabozzi A, Gennaro M, Borzacchiello A (2022) Hyaluronic acid-based wound dressing with antimicrobial properties for wound healing application. Appl Sci 12(6):3091. https://doi.org/10.3390/app12063091
Samadian H, Maleki H, Allahyari Z, Jaymand M (2020) Natural polymers-based light-induced hydrogels: promising biomaterials for biomedical applications. Coord Chem Rev 420:213432. https://doi.org/10.1016/j.ccr.2020.213432
Shahravi Z, Mehdikhani M, Amirkhani MA, Sisakht MM, Farsaei S (2023) Multifunctional electrospun polyvinyl alcohol/gellan gum/polycaprolactone nanofibrous membrane containing pentoxifylline to accelerate wound healing. Polym Bull 80:2217–2237. https://doi.org/10.1007/s00289-022-04446-1
Shen S, Chen X, Shen Z, Chen H (2021) Marine polysaccharide for wound dressing applications: an overview. Pharmaceutics 13:1666. https://doi.org/10.3390/pharmaceutics13101666
Sheorain J, Mehra M, Thakur R, Grewal S, Kumari S (2019) In vitro anti-inflammatory and antioxidant potential of thymol loaded bipolymeric (tragacanth gum/chitosan) nanocarrier. Int J Biol Macromol 125:1069–1074. https://doi.org/10.1016/j.ijbiomac.2018.12.095
Stathopoulou MEK, Banti CN, Kourkoumelis N, Hatzidimitriou AG, Kalampounias AG, Hadjikakou SK (2018) Silver complex of salicylic acid and its hydrogel-cream in wound healing chemotherapy. J Inorg Biochem 181:41–55. https://doi.org/10.1016/j.jinorgbio.2018.01.004
Üstündağ Okur N, Hökenek N, Okur ME, Ayla Ş, Yoltaş A, Siafaka PI, Cehver E (2019) An alternative approach to wound healing field; new composite films from natural polymers for mupirocin dermal delivery. Saudi Pharm J 27(5):738–752. https://doi.org/10.1016/j.jsps.2019.04.010
Walczak M, Michalska-Sionkowska M, Kaczmarek B, Sionkowska A (2020) Surface and antibacterial properties of thin films based on collagen and thymol. Mater Today Commun 22:100949. https://doi.org/10.1016/j.mtcomm.2020.100949
Wang W, Ummartyotin S, Narain R (2023) Advances and challenges on hydrogels for wound dressing. Curr Opin Biomed Eng 26:100443. https://doi.org/10.1016/j.cobme.2022.100443
Yaşayan G, Karaca G, Akgüner ZP, Bal-Öztürk A (2021) Chitosan/collagen composite films as wound dressings encapsulating allantoin and lidocaine hydrochloride. Int J Polym Mater Polym Biomater 70(9):623–635. https://doi.org/10.1080/00914037.2020.1740993
Yue Y, Gong X, Jiao W, Li Y, Yin X, Si Y, Yu J, Ding B (2021) In-situ electrospinning of thymol-loaded polyurethane fibrous membranes for waterproof, breathable, and antibacterial wound dressing application. J Colloid Interface Sci 592:310–318. https://doi.org/10.1016/j.jcis.2021.02.048
Acknowledgments
The authors are grateful for the support of Assoc. Prof. Ayça Bal Öztürk with mechanical tests.
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This work was supported by the Çankırı Karatekin University Scientific Research Projects Coordination Office (Grant Number: MF211221L23).
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All authors contributed to the study’s conception and design. Formal analysis and investigation: G.A. and B.Ö., Data collection and analysis: G.A. and B.Ö., Writing-first draft preparation: B.Ö. and Z.Ö., Writing-review and editing: Z.Ö., Supervision: Z.Ö.
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Acar, G., Özkahraman, B. & Özbaş, Z. Thymol incorporated gellan gum/carboxymethyl cellulose/hyaluronic acid films for wound dressings applications. Cellulose 30, 9517–9528 (2023). https://doi.org/10.1007/s10570-023-05451-x
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DOI: https://doi.org/10.1007/s10570-023-05451-x