Abstract
In this research, a novel drug-loaded nanofibrous membrane composed of polyvinyl alcohol/gellan gum (PVA/GG) on polycaprolactone (PCL) as a scaffold to deliver pentoxifylline (PTX) was fabricated for wound healing. The morphology and mean fiber diameter of scaffolds were characterized. Mechanical properties, wettability, degradation rate, and drug delivery were evaluated for each fibrous scaffold. The cytotoxicity evaluation of the samples was conducted using human dermal fibroblasts (HDFs). The results confirmed that PVA/GG with the ratio of 50:50 has an optimum fibers’ diameter ranging between 86 and 110 nm, over 76% of porosity, and a desired mechanical properties for skin tissue engineering. Ultimate tensile strength (UTS) and elastic modulus of the PTX-loaded scaffold (PVA/GG 50:50) decreased compared with the non-loaded one. Adding 20 mg/ml PTX to the scaffold caused a considerable increase in the samples’ degradation. Furthermore, the PTX-loaded scaffold showed a higher wettability and roughness in comparison with the one without PTX. The PTX was released from the fibrous membrane up to 120 h. HDFs’ viability and adhesion were significantly higher for drug-loaded scaffolds compared with the control group. In summary, the nanofibrous composite scaffold made of PTX-PVA-GG/PCL could be used as a suitable wound dressing for speeding up wound regeneration.
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Nilforoushzadeh MA et al (2017) Regenerative medicine applications in wound care. Curr Stem Cell Res Ther 12(8):658–674
Li Y et al (2015) Bacterial cellulose–hyaluronan nanocomposite biomaterials as wound dressings for severe skin injury repair. J Mater Chem B 3(17):3498–3507
Gajiwala K, Gajiwala AL (2004) Evaluation of lyophilized, gamma-irradiated amnion as a biological dressing. Cell Tissue Bank 5(2):73–80
Lee SH, Jeong SK, Ahn SK (2006) An update of the defensive barrier function of skin. Yonsei Med J 47(3):293–306
Flanagan M (2000) The physiology of wound healing. J Wound Care 9(6):299–300
Atiyeh BS, Hayek SN, Gunn SW (2005) New technologies for burn wound closure and healing—review of the literature. Burns 31(8):944–956
Mabrouk M, Beherei HH, Das DB (2020) Recent progress in the fabrication techniques of 3D scaffolds for tissue engineering. Mater Sci Eng C 110:110716
Saudi A et al (2019) Promoting neural cell proliferation and differentiation by incorporating lignin into electrospun poly (vinyl alcohol) and poly (glycerol sebacate) fibers. Mater Sci Eng, C 104:110005
Abel SB, Ballarin FM, Abraham GA (2020) Combination of electrospinning with other techniques for the fabrication of 3D polymeric and composite nanofibrous scaffolds with improved cellular interactions. Nanotechnology 31(17):172002
Bigham A et al (2019) Electrophoretically deposited mesoporous magnesium silicate with ordered nanopores as an antibiotic-loaded coating on surface-modified titanium. Mater Sci Eng C 96:765–775
Saudi A, Zebarjad SM, Alipour H, Katoueizadeh E, Alizadeh A, Rafienia M 2022) A study on the role of multi-walled carbon nanotubes on the properties of electrospun poly (caprolactone)/poly (glycerol sebacate) scaffold for nerve tissue applications. Mater Chem Phys 125868
Gugulothu D, Barhoum A, Nerella R, Ajmer R, Bechlany M (2018) Fabrication of nanofibers: electrospinning and non-electrospinning techniques. Handb Nanofibers 1–34
Saudi A, Zebarjad SM, Salehi H, Katoueizadeh E, Alizadeh A (2022) Assessing physicochemical, mechanical, and in vitro biological properties of polycaprolactone/poly (glycerol sebacate)/hydroxyapatite composite scaffold for nerve tissue engineering. Mater Chem Phys 275:125224
Huang Z-M, Zhang Y-Z, Kotaki M, Ramakrishna S (2003) A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos Sci Technol 63(15):2223–2253
Vashisth P, Pruthi PA, Singh RP, Pruthi V (2014) Process optimization for fabrication of gellan based electrospun nanofibers. Carbohyd Polym 109:16–21
Sattary M, Kefayat A, Bigham A, Rafienia M (2020) Polycaprolactone/gelatin/hydroxyapatite nanocomposite scaffold seeded with Stem cells from human exfoliated deciduous teeth to enhance bone repair: in vitro and in vivo studies. Mater Technol 37:1–14
Saudi A, Rafienia M, Zargar Kharazi A, Salehi H, Zarrabi A, Karevan M (2019) Design and fabrication of poly (glycerol sebacate)-based fibers for neural tissue engineering: synthesis, electrospinning, and characterization. Polym Adv Technol 30(6):1427–1440
Baghbadorani MA, Bigham A, Rafienia M, Salehi H (2021) A ternary nanocomposite fibrous scaffold composed of poly (ε-caprolactone)/gelatin/gehlenite (Ca2Al2SiO7): Physical, chemical, and biological properties in vitro. Polym Adv Technol 32(2):582–598
Rastegar S, Mehdikhani M, Bigham A, Poorazizi E, Rafienia M (2021) Polyglycerol sebacate/polycaprolactone/carbon quantum dots fibrous scaffold as a multifunctional platform for cardiac tissue engineering. Mater Chem Phys 266:124543
Duan H et al (2013) Engineering of epidermis skin grafts using electrospun nanofibrous gelatin/polycaprolactone membranes. Int J Nanomed 8:2077
Karbowniczek JE, Kaniuk Ł, Berniak K, Gruszczyński A, Stachewicz U (2021) Enhanced cells anchoring to electrospun hybrid scaffolds with PHBV and HA particles for bone tissue regeneration. Front Bioeng Biotech 9:70
Acik G, Altinkok C, Tasdelen MA (2018) Synthesis and characterization of polypropylene-graft-poly (l-lactide) copolymers by CuAAC click chemistry. J Polym Sci Part A Polym Chem 56(22):2595–2601
Acik G, Sey E, Tasdelen M (2018) Polypropylene-based graft copolymers via CuAAC click chemistry. Express Polym Lett 12:418
Joseph B, Augustine R, Kalarikkal N, Thomas S, Seantier B, Grohens Y (2019) Recent advances in electrospun polycaprolactone based scaffolds for wound healing and skin bioengineering applications. Mater Today Commun 19:319–335
Zheng Y et al (2018) Gelatin-based hydrogels blended with gellan as an injectable wound dressing. ACS Omega 3(5):4766–4775
Azam NM, Amin K (2017) The physical and mechanical properties of gellan gum films incorporated manuka honey as wound dressing materials. In: IOP Conference Series: Materials Science and Engineering 209(1):012027.
Vashisth P, Nikhil K, Roy P, Pruthi PA, Singh RP, Pruthi V (2016) A novel gellan–PVA nanofibrous scaffold for skin tissue regeneration: Fabrication and characterization. Carbohyd Polym 136:851–859
Cencetti C et al (2012) Preparation and characterization of antimicrobial wound dressings based on silver, gellan, PVA and borax. Carbohyd Polym 90(3):1362–1370
Matar GH, Andac M (2020) Antibacterial efficiency of silver nanoparticles-loaded locust bean gum/polyvinyl alcohol hydrogels. Polym Bull 1–19
Chronakis IS (2005) Novel nanocomposites and nanoceramics based on polymer nanofibers using electrospinning process—a review. J Mater Process Technol 167(2–3):283–293
Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (1999) Pentoxifylline inhibits TNF-α production from human alveolar macrophages. Am J Respir Crit Care Med 159(2):508–511
Ahmadi M, Khalili H (2016) Potential benefits of pentoxifylline on wound healing. Expert Rev Clin Pharmacol 9(1):129–142
Kornreich B, Enyeart M, Jesty S, Nydam D, Divers T (2010) The effects of pentoxifylline on equine platelet aggregation. J Vet Intern Med 24(5):1196–1202
Amini A, Velaei K, Bayat M, Dadpay M, Nourozian M (2013) The effects of pentoxifylline on the wound healing process in a rat experimental pressure sore model. Anat Sci J 10(1):15–24
Babaei S, Bayat M (2015) Pentoxifylline accelerates wound healing process by modulating gene expression of MMP-1, MMP-3, and TIMP-1 in normoglycemic rats. J Invest Surg 28(4):196–201
Najafi E et al (2018) Topical pentoxifylline for pressure ulcer treatment: a randomized, double-blind, placebo-controlled clinical trial. J Wound Care 27(8):495–502
Hassan I, Dorjay K, Anwar P (2014) Pentoxifylline and its applications in dermatology. Indian Dermatol Online J 5(4):510
Aghajani A, Kazemi T, Enayatifard R, Amiri FT, Narenji M (2020) Investigating the skin penetration and wound healing properties of niosomal pentoxifylline cream. Eur J Pharm Sci 151:105434
Lin H-Y, Yeh C-T (2010) Alginate-crosslinked chitosan scaffolds as pentoxifylline delivery carriers. J Mater Sci Mater Med 21(5):1611–1620
Amini F, Semnani D, Karbasi S, Banitaba SN (2019) A novel bilayer drug-loaded wound dressing of PVDF and PHB/Chitosan nanofibers applicable for post-surgical ulcers. Int J Polym Mater Polym Biomater 68(13):772–777
Toloue EB, Karbasi S, Salehi H, Rafienia M (2019) Potential of an electrospun composite scaffold of poly (3-hydroxybutyrate)-chitosan/alumina nanowires in bone tissue engineering applications. Mater Sci Eng, C 99:1075–1091
Li Z, Wang C (2013) Effects of working parameters on electrospinning. In one-dimensional nanostructures. Springer, pp 15–28
Castkova K et al (2020) Structure–properties relationship of electrospun PVDF fibers. Nanomaterials 10(6):1221
Mehta PP, Pawar VS (2018) Electrospun nanofiber scaffolds: technology and applications. In applications of nanocomposite materials in drug delivery. Elsevier, pp 509–573
Gharibi R, Yeganeh H, Rezapour-Lactoee A, Hassan ZM (2015) Stimulation of wound healing by electroactive, antibacterial, and antioxidant polyurethane/siloxane dressing membranes: in vitro and in vivo evaluations. ACS Appl Mater Interfaces 7(43):24296–24311. https://doi.org/10.1021/acsami.5b08376
Amini S et al (2020) Application of electrospun polycaprolactone fibers embedding lignin nanoparticle for peripheral nerve regeneration: in vitro and in vivo study. Int J Biol Macromol 159:154–173
Zaman HU, Islam J, Khan MA, Khan RA (2011) Physico-mechanical properties of wound dressing material and its biomedical application. J Mech Behav Biomed Mater 4(7):1369–1375
Teixeira MA, Amorim MTP, Felgueiras HP (2020) Poly (vinyl alcohol)-based nanofibrous electrospun scaffolds for tissue engineering applications. Polymers 12(1):7
Gallagher A, Ní Annaidh A, Bruyère K (2012) Dynamic tensile properties of human skin. In: IRCOBI Conference 2012, 12–14 September 2012, Dublin (Ireland), 2012: International Research Council on the Biomechanics of Injury.
Annaidh AN, Bruyère K, Destrade M, Gilchrist MD, Otténio M (2012) Characterization of the anisotropic mechanical properties of excised human skin. J Mech Behav Biomed Mater 5(1):139–148
Shuwaili AHA, Rasool BKA, Abdulrasool AA (2016) Optimization of elastic transfersomes formulations for transdermal delivery of pentoxifylline. Eur J Pharm Biopharm 102:101–114
Qiang Y, Zhang S, Tan B, Chen S (2018) Evaluation of Ginkgo leaf extract as an eco-friendly corrosion inhibitor of X70 steel in HCl solution. Corros Sci 133:6–16
Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani MH, Ramakrishna S (2010) Bio-functionalized PCL nanofibrous scaffolds for nerve tissue engineering. Mater Sci Eng, C 30(8):1129–1136
Mermoux M, Chabre Y, Rousseau A (1991) FTIR and 13C NMR study of graphite oxide. Carbon 29(3):469–474. https://doi.org/10.1016/0008-6223(91)90216-6
Silva-Correia J et al (2011) Gellan gum-based hydrogels for intervertebral disc tissue-engineering applications. J Tissue Eng Regen Med 5(6):e97–e107
Hu K, Zhuang J, Ding J, Ma Z, Wang F, Zeng X (2017) Influence of biomacromolecule DNA corrosion inhibitor on carbon steel. Corros Sci 125:68–76
Moore DJ, Sills RH, Mendelsohn R (1995) Peroxidation of erythrocytes: FTIR spectroscopy studies of extracted lipids, isolated membranes, and intact cells. Biospectroscopy 1(2):133–140
Lin H-Y, Yeh C-T (2010) Controlled release of pentoxifylline from porous chitosan-pectin scaffolds. Drug Delivery 17(5):313–321
Zhu H, Nyström M (1998) Cleaning results characterized by flux, streaming potential and FTIR measurements. Colloids Surf A Physicochem Eng Asp 138(2):309–321. https://doi.org/10.1016/S0927-7757(97)00072-1
Pawlak A, Mucha M (2003) Thermogravimetric and FTIR studies of chitosan blends. Thermochim Acta 396(1):153–166. https://doi.org/10.1016/S0040-6031(02)00523-3
van Oss CJ (2020) Cell Interactions and surface hydrophilicity: influence of Lewis acid-base and electrostatic forces In cell electrophoresis. CRC Press, pp 219–239
Nuraje N, Khan WS, Lei Y, Ceylan M, Asmatulu R (2013) Superhydrophobic electrospun nanofibers. J Mater Chem A 1(6):1929–1946
Silvestro I et al (2020) Hyaluronic acid reduces bacterial fouling and promotes fibroblasts’ adhesion onto chitosan 2D-wound dressings. Int J Mol Sci 21(6):2070
Raja IS et al. (2022) Predominant factor influencing cellular behaviors on electrospun nanofibrous scaffolds: wettability or surface morphology? Mater Des 110580
Hayes T, Su B (2011) Wound dressings. In electrospinning for tissue regeneration. Elsevier, pp 317–339
Bettencourt AF et al (2010) Biodegradation of acrylic-based resins: A review. Dent Mater 26(5):e171–e180
Kim H-S, Kim H-J (2008) Enhanced hydrolysis resistance of biodegradable polymers and bio-composites. Polym Degrad Stab 93(8):1544–1553
Kumar SSD, Abrahamse H (2020) Advancement of nanobiomaterials to deliver natural compounds for tissue engineering applications. Int J Mol Sci 21(18):6752
Milosevic M et al (2020) Preparation and modeling of three-layered PCL/PLGA/PCL fibrous scaffolds for prolonged drug release. Sci Rep 10(1):1–12
Yan E et al (2020) pH-sensitive core-shell electrospun nanofibers based on polyvinyl alcohol/polycaprolactone as a potential drug delivery system for the chemotherapy against cervical cancer. J Drug Deliv Sci Technol 55:101455
Sun X-Z, Williams GR, Hou X-X, Zhu L-M (2013) Electrospun curcumin-loaded fibers with potential biomedical applications. Carbohyd Polym 94(1):147–153
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The authors gratefully acknowledge the support for this work by the University of Isfahan (financial and scientific) and Tehran University of Medical Sciences (scientific).
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Shahravi, Z., Mehdikhani, M., Amirkhani, M.A. et al. Multifunctional electrospun polyvinyl alcohol/gellan gum/polycaprolactone nanofibrous membrane containing pentoxifylline to accelerate wound healing. Polym. Bull. 80, 2217–2237 (2023). https://doi.org/10.1007/s00289-022-04446-1
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DOI: https://doi.org/10.1007/s00289-022-04446-1