Traditional wound dressings have not been able to satisfy the needs of the regenerative medicine biomedical area. With the aim of improving tissue regeneration, nanofiber-based wound dressings fabricated by electrospinning (ES) processes have emerged as a powerful approach. Nowadays, nanofiber-based bioactive dressings are mainly developed with a combination of natural and synthetic polymers, such as polycaprolactone (PCL) and chitosan (CHI). Accordingly, herein, PCL/CHI nanofibers have been developed with varying PCL:CHI weight ratios (9:1, 8:2 and 7:3) or CHI viscosities (20, 100 and 600 mPa·s) using a novel alternating current ES (ACES) process. Such nanofibers were thoroughly characterized by determining physicochemical and nanomechanical properties, along with wettability, absorption capacity and hydrolytic plus enzymatic stability. Furthermore, PCL/CHI nanofiber biological safety was validated in terms of cytocompatibility and hemocompatibility (hemolysis < 2%), in addition to a notable antibacterial performance (bacterial reductions of 99.90% for S. aureus and 99.91% for P. aeruginosa). Lastly, the enhanced wound healing activity of PCL/CHI nanofibers was confirmed thanks to their ability to remarkably promote cell proliferation, which make them ideal candidates for long-term applications such as wound dressings.

Department of Physics Faculty of Science Humanities and Education Technical University of Liberec Studentská 1402 2 461 17 Liberec Czech Republic

i Med S Coop Alava Technology Park Albert Einstein 15 nave 15 01510 Vitoria Gasteiz Spain

See more in PubMed

Ibrahim H.M., Klingner A. A review on electrospun polymeric nanofibers: Production parameters and potential applications. Polym. Test. 2020;90:106647. doi: 10.1016/j.polymertesting.2020.106647. DOI

Zhang X., Shi X., Gautrot J.E., Peijs T. Nanoengineered electrospun fibers and their biomedical applications: A review. Nanocomposites. 2021;7:1–34. doi: 10.1080/20550324.2020.1857121. DOI

Rahmati M., Mills D.K., Urbanska A.M., Saeb M.R., Venugopal J.R., Ramakrishna S., Mozafari M. Electrospinning for tissue engineering applications. Prog. Mater. Sci. 2021;117:100721. doi: 10.1016/j.pmatsci.2020.100721. DOI

Zheng Q., Xi Y., Weng Y. Functional electrospun nanofibers: Fabrication, properties, and applications in wound-healing process. RSC Adv. 2024;14:3359–3378. doi: 10.1039/D3RA07075A. PubMed DOI PMC

Zhang X., Wang Y., Gao Z., Mao X., Cheng J., Huang L., Tang J. Advances in wound dressing based on electrospinning nanofibers. J. Appl. Polym. Sci. 2024;141:e54746. doi: 10.1002/app.54746. DOI

Liu X., Xu H., Zhang M., Yu D.-G. Electrospun Medicated Nanofibers for Wound Healing: Review. Membranes. 2021;11:770. doi: 10.3390/membranes11100770. PubMed DOI PMC

Rezvani Ghomi E., Niazi M., Ramakrishna S. The evolution of wound dressings: From traditional to smart dressings. Polym. Adv. Technol. 2023;34:520–530. doi: 10.1002/pat.5929. DOI

Schoukens G. Advanced Textiles for Wound Care. Elsevier; Amsterdam, The Netherlands: 2019. Bioactive dressings to promote wound healing; pp. 135–167.

Mogoşanu G.D., Grumezescu A.M. Natural and synthetic polymers for wounds and burns dressing. Int. J. Pharm. 2014;463:127–136. doi: 10.1016/j.ijpharm.2013.12.015. PubMed DOI

Gobi R., Ravichandiran P., Babu R.S., Yoo D.J. Biopolymer and Synthetic Polymer-Based Nanocomposites in Wound Dressing Applications: A Review. Polymers. 2021;13:1962. doi: 10.3390/polym13121962. PubMed DOI PMC

Joseph B., Augustine R., Kalarikkal N., Thomas S., Seantier B., Grohens Y. Recent advances in electrospun polycaprolactone based scaffolds for wound healing and skin bioengineering applications. Mater. Today Commun. 2019;19:319–335. doi: 10.1016/j.mtcomm.2019.02.009. DOI

Azimi B., Maleki H., Zavagna L., De la Ossa J.G., Linari S., Lazzeri A., Danti S. Bio-Based Electrospun Fibers for Wound Healing. J. Funct. Biomater. 2020;11:67. doi: 10.3390/jfb11030067. PubMed DOI PMC

Angel N., Li S., Yan F., Kong L. Recent advances in electrospinning of nanofibers from bio-based carbohydrate polymers and their applications. Trends Food Sci. Technol. 2022;120:308–324. doi: 10.1016/j.tifs.2022.01.003. DOI

Chen S., Tian H., Mao J., Ma F., Zhang M., Chen F., Yang P. Preparation and application of chitosan-based medical electrospun nanofibers. Int. J. Biol. Macromol. 2023;226:410–422. doi: 10.1016/j.ijbiomac.2022.12.056. PubMed DOI

Ibrahim M.A., Alhalafi M.H., Emam E.-A.M., Ibrahim H., Mosaad R.M. A Review of Chitosan and Chitosan Nanofiber: Preparation, Characterization, and Its Potential Applications. Polymers. 2023;15:2820. doi: 10.3390/polym15132820. PubMed DOI PMC

Valachová K., El Meligy M.A., Šoltés L. Hyaluronic acid and chitosan-based electrospun wound dressings: Problems and solutions. Int. J. Biol. Macromol. 2022;206:74–91. doi: 10.1016/j.ijbiomac.2022.02.117. PubMed DOI

Shalumon K.T., Anulekha K.H., Girish C.M., Prasanth R., Nair S.V., Jayakumar R. Single step electrospinning of chitosan/poly(caprolactone) nanofibers using formic acid/acetone solvent mixture. Carbohydr. Polym. 2010;80:413–419. doi: 10.1016/j.carbpol.2009.11.039. DOI

Van der Schueren L., Steyaert I., De Schoenmaker B., De Clerck K. Polycaprolactone/chitosan blend nanofibres electrospun from an acetic acid/formic acid solvent system. Carbohydr. Polym. 2012;88:1221–1226. doi: 10.1016/j.carbpol.2012.01.085. DOI

Xue J., Wu T., Dai Y., Xia Y. Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications. Chem. Rev. 2019;119:5298–5415. doi: 10.1021/acs.chemrev.8b00593. PubMed DOI PMC

Sivan M., Madheswaran D., Hauzerova S., Novotny V., Hedvicakova V., Jencova V., Kostakova E.K., Schindler M., Lukas D. AC electrospinning: Impact of high voltage and solvent on the electrospinnability and productivity of polycaprolactone electrospun nanofibrous scaffolds. Mater. Today Chem. 2022;26:101025. doi: 10.1016/j.mtchem.2022.101025. DOI

Sivan M., Madheswaran D., Valtera J., Kostakova E.K., Lukas D. Alternating current electrospinning: The impacts of various high-voltage signal shapes and frequencies on the spinnability and productivity of polycaprolactone nanofibers. Mater. Des. 2022;213:110308. doi: 10.1016/j.matdes.2021.110308. DOI

Farkas B., Balogh A., Farkas A., Marosi G., Nagy Z.K. Frequency and waveform dependence of alternating current electrospinning and their uses for drug dissolution enhancement. Int. J. Pharm. 2020;586:119593. doi: 10.1016/j.ijpharm.2020.119593. PubMed DOI

Balogh A., Cselkó R., Démuth B., Verreck G., Mensch J., Marosi G., Nagy Z.K. Alternating current electrospinning for preparation of fibrous drug delivery systems. Int. J. Pharm. 2015;495:75–80. doi: 10.1016/j.ijpharm.2015.08.069. PubMed DOI

Farkas B., Balogh A., Cselkó R., Molnár K., Farkas A., Borbás E., Marosi G., Nagy Z.K. Corona alternating current electrospinning: A combined approach for increasing the productivity of electrospinning. Int. J. Pharm. 2019;561:219–227. doi: 10.1016/j.ijpharm.2019.03.005. PubMed DOI

Jirkovec R., Holec P., Hauzerova S., Samkova A., Kalous T., Chvojka J. Preparation of a Composite Scaffold from Polycaprolactone and Hydroxyapatite Particles by Means of Alternating Current Electrospinning. ACS Omega. 2021;6:9234–9242. doi: 10.1021/acsomega.1c00644. PubMed DOI PMC

Pokorny P., Kostakova E., Sanetrnik F., Mikes P., Chvojka J., Kalous T., Bilek M., Pejchar K., Valtera J., Lukas D. Effective AC needleless and collectorless electrospinning for yarn production. Phys. Chem. Chem. Phys. 2014;16:26816–26822. doi: 10.1039/C4CP04346D. PubMed DOI

Anisiei A., Oancea F., Marin L. Electrospinning of chitosan-based nanofibers: From design to prospective applications. Rev. Chem. Eng. 2023;39:31–70. doi: 10.1515/revce-2021-0003. DOI

Tamilarasi G.P., Sabarees G., Manikandan K., Gouthaman S., Alagarsamy V., Solomon V.R. Advances in electrospun chitosan nanofiber biomaterials for biomedical applications. Mater. Adv. 2023;4:3114–3139. doi: 10.1039/D3MA00010A. DOI

Oviedo M., Montoya Y., Agudelo W., García-García A., Bustamante J. Effect of Molecular Weight and Nanoarchitecture of Chitosan and Polycaprolactone Electrospun Membranes on Physicochemical and Hemocompatible Properties for Possible Wound Dressing. Polymers. 2021;13:4320. doi: 10.3390/polym13244320. PubMed DOI PMC

Sohi A.N., Naderi-Manesh H., Soleimani M., Mirzaei S., Delbari M., Dodel M. Influence of Chitosan Molecular Weight and Poly(ethylene oxide): Chitosan Proportion on Fabrication of Chitosan Based Electrospun Nanofibers. Polym. Sci. Ser. A. 2018;60:471–482. doi: 10.1134/S0965545X18040077. DOI

Prasad T., Shabeena E.A., Vinod D., Kumary T.V., Anil Kumar P.R. Characterization and in vitro evaluation of electrospun chitosan/polycaprolactone blend fibrous mat for skin tissue engineering. J. Mater. Sci. Mater. Med. 2015;26:28. doi: 10.1007/s10856-014-5352-8. PubMed DOI

Steyaert I., Van der Schueren L., Rahier H., de Clerck K. An Alternative Solvent System for Blend Electrospinning of Polycaprolactone/Chitosan Nanofibres. Macromol. Symp. 2012;321–322:71–75. doi: 10.1002/masy.201251111. DOI

Roozbahani F., Sultana N., Fauzi Ismail A., Nouparvar H. Effects of Chitosan Alkali Pretreatment on the Preparation of Electrospun PCL/Chitosan Blend Nanofibrous Scaffolds for Tissue Engineering Application. J. Nanomater. 2013;2013:641502. doi: 10.1155/2013/641502. DOI

Test Methods for Primary Wound Dressings. Part 1: Aspects of Absorbency. ISO; Geneva, Switzerland: 2002.

Gefen A., Alves P., Beeckman D., Cullen B., Lázaro-Martínez J.L., Lev-Tov H., Najafi B., Santamaria N., Sharpe A., Swanson T., et al. How Should Clinical Wound Care and Management Translate to Effective Engineering Standard Testing Requirements from Foam Dressings? Mapping the Existing Gaps and Needs. Adv. Wound Care. 2024;13:34–52. doi: 10.1089/wound.2021.0173. PubMed DOI PMC

Biological Evaluation of Medical Devices—Tests for In Vitro Cytotoxicity. International Organization for Standarization; Geneva, Switzerland: 2009.

Nalezinková M. In vitro hemocompatibility testing of medical devices. Thromb. Res. 2020;195:146–150. doi: 10.1016/j.thromres.2020.07.027. PubMed DOI

Shanmugam P.S.T., Sampath T., Jagadeeswaran I., Krithaksha V., Bhalerao V.P., Thamizharasan S. Biocompatibility Protocols for Medical Devices and Materials. Elsevier; Amsterdam, The Netherlands: 2023. Hemocompatibility; pp. 91–125.

Kumirska J., Czerwicka M., Kaczyński Z., Bychowska A., Brzozowski K., Thöming J., Stepnowski P. Application of Spectroscopic Methods for Structural Analysis of Chitin and Chitosan. Mar. Drugs. 2010;8:1567–1636. doi: 10.3390/md8051567. PubMed DOI PMC

Lazaridou M., Nanaki S., Zamboulis A., Papoulia C., Chrissafis K., Klonos P.A., Kyritsis A., Vergkizi-Nikolakaki S., Kostoglou M., Bikiaris D.N. Super absorbent chitosan-based hydrogel sponges as carriers for caspofungin antifungal drug. Int. J. Pharm. 2021;606:120925. doi: 10.1016/j.ijpharm.2021.120925. PubMed DOI

Can-Herrera L.A., Oliva A.I., Dzul-Cervantes M.A.A., Pacheco-Salazar O.F., Cervantes-Uc J.M. Morphological and Mechanical Properties of Electrospun Polycaprolactone Scaffolds: Effect of Applied Voltage. Polymers. 2021;13:662. doi: 10.3390/polym13040662. PubMed DOI PMC

Weißpflog J., Vehlow D., Müller M., Kohn B., Scheler U., Boye S., Schwarz S. Characterization of chitosan with different degree of deacetylation and equal viscosity in dissolved and solid state—Insights by various complimentary methods. Int. J. Biol. Macromol. 2021;171:242–261. doi: 10.1016/j.ijbiomac.2021.01.010. PubMed DOI

Jhala D., Rather H., Vasita R. Polycaprolactone–chitosan nanofibers influence cell morphology to induce early osteogenic differentiation. Biomater. Sci. 2016;4:1584–1595. doi: 10.1039/C6BM00492J. PubMed DOI

Miguel S.P., Figueira D.R., Simões D., Ribeiro M.P., Coutinho P., Ferreira P., Correia I.J. Electrospun polymeric nanofibres as wound dressings: A review. Colloids Surf. B Biointerfaces. 2018;169:60–71. doi: 10.1016/j.colsurfb.2018.05.011. PubMed DOI

Yang S., Li X., Liu P., Zhang M., Wang C., Zhang B. Multifunctional Chitosan/Polycaprolactone Nanofiber Scaffolds with Varied Dual-Drug Release for Wound-Healing Applications. ACS Biomater. Sci. Eng. 2020;6:4666–4676. doi: 10.1021/acsbiomaterials.0c00674. PubMed DOI

Salgado C.L., Sanchez E.M.S., Mano J.F., Moraes A.M. Characterization of chitosan and polycaprolactone membranes designed for wound repair application. J. Mater. Sci. 2012;47:659–667. doi: 10.1007/s10853-011-5836-6. DOI

Miao S., Cao X., Lu M., Liu X. Tailoring micro/nano-materials with special wettability for biomedical devices. Biomed. Technol. 2023;2:15–30. doi: 10.1016/j.bmt.2022.11.005. DOI

Raman A., Jayan J.S., Deeraj B.D.S., Saritha A., Joseph K. Electrospun Nanofibers as Effective Superhydrophobic Surfaces: A Brief review. Surf. Interfaces. 2021;24:101140. doi: 10.1016/j.surfin.2021.101140. DOI

Martins A., Pinho E.D., Faria S., Pashkuleva I., Marques A.P., Reis R.L., Neves N.M. Surface Modification of Electrospun Polycaprolactone Nanofiber Meshes by Plasma Treatment to Enhance Biological Performance. Small. 2009;5:1195–1206. doi: 10.1002/smll.200801648. PubMed DOI

Fadaie M., Mirzaei E., Geramizadeh B., Asvar Z. Incorporation of nanofibrillated chitosan into electrospun PCL nanofibers makes scaffolds with enhanced mechanical and biological properties. Carbohydr. Polym. 2018;199:628–640. doi: 10.1016/j.carbpol.2018.07.061. PubMed DOI

He C., Yu B., Lv Y., Huang Y., Guo J., Li L., Chen M., Zheng Y., Liu M., Guo S., et al. Biomimetic Asymmetric Composite Dressing by Electrospinning with Aligned Nanofibrous and Micropatterned Structures for Severe Burn Wound Healing. ACS Appl. Mater. Interfaces. 2022;14:32799–32812. doi: 10.1021/acsami.2c04323. PubMed DOI

Browning P., White R.J., Rowell T. Comparative evaluation of the functional properties of superabsorbent dressings and their effect on exudate management. J. Wound Care. 2016;25:452–462. doi: 10.12968/jowc.2016.25.8.452. PubMed DOI

Lazaridou M., Moroni S., Klonos P., Kyritsis A., Bikiaris D.N., Lamprou D.A. 3D-printed hydrogels based on amphiphilic chitosan derivative loaded with levofloxacin for wound healing applications. Int. J. Polym. Mater. Polym. Biomater. 2024:1–18. doi: 10.1080/00914037.2024.2314610. DOI

Thomas L.V. Biomedical Product and Materials Evaluation. Elsevier; Amsterdam, The Netherlands: 2022. Evaluation of polymeric biomaterials used as wound care products; pp. 63–94.

Boinovich L., Emelyanenko A.M., Pashinin A.S. Analysis of Long-Term Durability of Superhydrophobic Properties under Continuous Contact with Water. ACS Appl. Mater. Interfaces. 2010;2:1754–1758. doi: 10.1021/am100241s. PubMed DOI

Verho T., Bower C., Andrew P., Franssila S., Ikkala O., Ras R.H.A. Mechanically Durable Superhydrophobic Surfaces. Adv. Mater. 2011;23:673–678. doi: 10.1002/adma.201003129. PubMed DOI

Dias J.R., Sousa A., Augusto A., Bártolo P.J., Granja P.L. Electrospun Polycaprolactone (PCL) Degradation: An In Vitro and In Vivo Study. Polymers. 2022;14:3397. doi: 10.3390/polym14163397. PubMed DOI PMC

Poshina D.N., Raik S.V., Poshin A.N., Skorik Y.A. Accessibility of chitin and chitosan in enzymatic hydrolysis: A review. Polym. Degrad. Stab. 2018;156:269–278. doi: 10.1016/j.polymdegradstab.2018.09.005. DOI

Balusamy B., Senthamizhan A., Uyar T. Electrospun Materials for Tissue Engineering and Biomedical Applications. Elsevier; Amsterdam, The Netherlands: 2017. In vivo safety evaluations of electrospun nanofibers for biomedical applications; pp. 101–113.

Alavi M., Nokhodchi A. Antimicrobial and wound healing activities of electrospun nanofibers based on functionalized carbohydrates and proteins. Cellulose. 2022;29:1331–1347. doi: 10.1007/s10570-021-04412-6. DOI

Serra R., Grande R., Butrico L., Rossi A., Settimio U.F., Caroleo B., Amato B., Gallelli L., De Franciscis S. Chronic wound infections: The role of Pseudomonas aeruginosa and Staphylococcus aureus. Expert Rev. Anti-Infect. Ther. 2015;13:605–613. doi: 10.1586/14787210.2015.1023291. PubMed DOI

Bagheri M., Validi M., Gholipour A., Makvandi P., Sharifi E. Chitosan nanofiber biocomposites for potential wound healing applications: Antioxidant activity with synergic antibacterial effect. Bioeng. Transl. Med. 2022;7:e10254. doi: 10.1002/btm2.10254. PubMed DOI PMC

Olmo J.A.-D., Ruiz-Rubio L., Pérez-Alvarez L., Sáez-Martínez V., Vilas-Vilela J.L. Antibacterial Coatings for Improving the Performance of Biomaterials. Coatings. 2020;10:139. doi: 10.3390/coatings10020139. DOI

Singh S., Young A., McNaught C.-E. The physiology of wound healing. Surgery. 2017;35:473–477. doi: 10.1016/j.mpsur.2017.06.004. DOI

de Oliveira Gonzalez A.C., Costa T.F., Andrade Z.d.A., Medrado A.R.A.P. Wound healing—A literature review. An. Bras. Dermatol. 2016;91:614–620. doi: 10.1590/abd1806-4841.20164741. PubMed DOI PMC

Landén N.X., Li D., Ståhle M. Transition from inflammation to proliferation: A critical step during wound healing. Cell. Mol. Life Sci. 2016;73:3861–3885. doi: 10.1007/s00018-016-2268-0. PubMed DOI PMC

Thermally Stabilised Poly(vinyl alcohol) Nanofibrous Materials Produced by Scalable Electrospinning: Applications in Tissue Engineering