ADVANCES IN ELECTROSPUN NANOFIBERS FOR SCAR REMOVAL AND TISSUE REGENERATION

Abstract

Nanotechnology has emerged as a promising approach for wound healing and scar removal, offering unique solutions to promote tissue regeneration and reduce scarring. Electrospun nanofibers have gained significant attention owing to their ability to mimic the extracellular matrix and provide an ideal environment for cell adhesion, proliferation, and differentiation. This comprehensive review explores recent advances in electrospinning-related nanotechnology for scar management, focusing on fabrication techniques, therapeutic applications, and safety considerations. Various electrospinning methods, including needle-based, needleless, melt, emulsion, and solution electrospinning, have been discussed, highlighting their advantages and limitations. The incorporation of therapeutic agents such as drugs, growth factors, and stem cells into electrospun nanofibers has been shown to promote wound healing and reduce scar formation. However, the biocompatibility and safety of these nanomaterials remain concerns, necessitating rigorous research to ensure their long-term safety and efficacy. The potential toxicity, biodistribution, immune response, and regulatory aspects of nanotechnology-based scar treatment have been critically examined. Despite these challenges, the future prospects of electrospun nanotechnology in scar management are promising, with the potential to revolutionize wound care and improve patient outcomes. Further research and development in this field are essential for transforming these innovative approaches into clinical practice.

Keywords

• Electrospun nanofibers
• Wound healing
• Scar management
• Nanotechnology
• Tissue regeneration

YARA İZİ GİDERME VE DOKU REJENERASYONU İÇİN ELEKTROSPUN NANOFİBERLERDEKİ GELİŞMELER

Abstract

Nanoteknoloji, doku rejenerasyonunu teşvik etmek ve yara izlerini azaltmak için benzersiz çözümler sunarak yara iyileşmesi ve yara izlerinin giderilmesi için umut verici bir yaklaşım olarak ortaya çıkmıştır. Elektrospunnanofiberler, hücre dışı matrisi taklit etme ve hücre yapışması, çoğalması ve farklılaşması için ideal bir ortam sağlama yetenekleri nedeniyle büyük ilgi görmüştür. Bu kapsamlı inceleme, yara izi yönetimi için elektroeğirme ile ilgili nanoteknolojideki son gelişmeleri araştırmakta, üretim tekniklerine, terapötik uygulamalara ve güvenlik hususlarına odaklanmaktadır. İğne tabanlı, iğnesiz, eriyik, emülsiyon ve çözelti elektrospinningdahil olmak üzere çeşitli elektrospinning yöntemleri, avantajları ve sınırlamaları vurgulanarak tartışılmıştır. İlaçlar, büyüme faktörleri ve kök hücreler gibi terapötik ajanların elektroeğirilmişnanolifleredahil edilmesinin yara iyileşmesini desteklediği ve yara izi oluşumunu azalttığı gösterilmiştir. Bununla birlikte, bu nanomalzemelerinbiyouyumluluğu ve güvenliği, uzun vadeli güvenlik ve etkinliklerini sağlamak için titiz araştırmalar gerektiren endişeler olmaya devam etmektedir. Nanoteknoloji temelli yara izi tedavisinin potansiyel toksisitesi, biyo-dağılımı, bağışıklık tepkisi ve düzenleyici yönleri eleştirel bir şekilde incelenmiştir. Bu zorluklara rağmen, yara yönetiminde elektrospunnanoteknolojinin gelecekteki beklentileri, yara bakımında devrim yaratma ve hasta sonuçlarını iyileştirme potansiyeli ile umut vericidir. Bu alanda daha fazla araştırma ve geliştirme yapılması, yara izi tedavisi için elzemdir.

Keywords

• Elektrospun nanofiberler
• Yara iyileşmesi
• Yara izi yönetimi
• Nanoteknoloji
• Doku rejenerasyonu

References

1. Haleem A, Javaid M, Singh RP, Rab S, Suman R. Applications of nanotechnology in medical field: a brief review. Global Health Journal 2023. https://doi. org/10. 1016/j. glohj. 2023. 02. 008.
2. Mackool RJ, Gittes GK, Longaker MT. Scarless healing. The fetal wound. Clin Plast Surg 1998;25:357–65.
3. Su C, Chen J, Xie X, Gao Z, Guan Z, Mo X, et al. Functionalized Electrospun Double-Layer Nanofibrous Scaffold for Wound Healing and Scar Inhibition. ACS Omega 2022;7:30137–48. https://doi. org/10. 1021/acsomega. 2c03222.
4. Barhoum A, Bechelany M, Hamdy Makhlouf AS. Handbook of Nanofibers. 2019. https://doi. org/10. 1007/978-3-319-53655-2.
5. Cavo M, Serio F, Kale NR, D’Amone E, Gigli G, del Mercato LL. Electrospun nanofibers in cancer research: from engineering of in vitro 3D cancer models to therapy. Biomater Sci 2020;8:4887–905. https://doi. org/10. 1039/D0BM00390E.
6. Pandey VK, Ajmal G, Upadhyay SN, Mishra PK. Nano-fibrous scaffold with curcumin for anti-scar wound healing. Int J Pharm 2020;589:119858. https://doi. org/10. 1016/j. ijpharm. 2020. 119858.
7. Contreras-Cáceres R, Cabeza L, Perazzoli G, Díaz A, López-Romero JM, Melguizo C, et al. Electrospun Nanofibers: Recent Applications in Drug Delivery and Cancer Therapy. Nanomaterials 2019;9:656. https://doi. org/10. 3390/nano9040656.
8. Contreras-Cáceres R, Cabeza L, Perazzoli G, Díaz A, López-Romero JM, Melguizo C, et al. Electrospun Nanofibers: Recent Applications in Drug Delivery and Cancer Therapy. Nanomaterials 2019;9:656. https://doi. org/10. 3390/nano9040656.

9. Takeo M, Lee W, Ito M. Wound healing and skin regeneration. Cold Spring Harb Perspect Med 2015;5:a023267. https://doi. org/10. 1101/cshperspect. a023267.
10. Tören E, Mazari A. Nano Transdermal Delivery Systems of Herbal Extracts for Dermatological Therapeutics and Skin Care. Open Journal of Nano 2024;9:77–105. https://doi. org/10. 56171/ojn. 1485463.
11. Tören E, Buzgo M, Mazari A, Khan M. Recent advances in biopolymer based electrospun nanomaterials for drug delivery systems. Polymers for Advanced Technologies 2024;35. https://doi. org/10. 1002/pat. 6309.
12. Martin P, Leibovich SJ. Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol 2005;15:599–607. https://doi. org/10. 1016/j. tcb. 2005. 09. 002.
13. Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med 2014;6:265sr6. https://doi. org/10. 1126/scitranslmed. 3009337.
14. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008;453:314–21. https://doi. org/10. 1038/nature07039.
15. Hinz B. The myofibroblast: paradigm for a mechanically active cell. J Biomech 2010;43:146–55. https://doi. org/10. 1016/j. jbiomech. 2009. 09. 020.
16. Wipff P-J, Rifkin DB, Meister J-J, Hinz B. Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. J Cell Biol 2007;179:1311–23. https://doi. org/10. 1083/jcb. 200704042.
17. Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol 2007;25:9–18. https://doi. org/10. 1016/j. clindermatol. 2006. 09. 007.
18. Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res 2012;49:35–43. https://doi. org/10. 1159/000339613.
19. Krafts KP. Tissue repair: The hidden drama. Organogenesis 2010;6:225–33. https://doi. org/10. 4161/org. 6. 4. 12555.
20. Enoch S, Leaper D. Basic science of wound healing. Surgery (Oxford) 2006;23:31–7. https://doi. org/10. 1016/j. mpsur. 2007. 11. 005.
21. Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 2007;127:514–25. https://doi. org/10. 1038/sj. jid. 5700701.
22. Gosain A, DiPietro LA. Aging and wound healing. World J Surg 2004;28:321–6. https://doi. org/10. 1007/s00268-003-7397-6.
23. Mathieu D, Linke J-C, Wattel F. Non-Healing Wounds. Handbook on Hyperbaric Medicine, 2006, p. 401–28. https://doi. org/10. 1007/1-4020-4448-8_20.
24. Schilling JA. Wound healing. Surg Clin North Am 1976;56:859–74. https://doi. org/10. 1016/s0039-6109(16)40983-7.
25. Broughton G, Janis JE, Attinger CE. Wound healing: an overview. Plast Reconstr Surg 2006;117:1e-S-32e-S. https://doi. org/10. 1097/01. prs. 0000222562. 60260. f9.
26. Darby IA, Laverdet B, Bonté F, Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol 2014;7:301–11. https://doi. org/10. 2147/CCID. S50046.
27. Caley MP, Martins VLC, O’Toole EA. Metalloproteinases and Wound Healing. Adv Wound Care (New Rochelle) 2015;4:225–34. https://doi. org/10. 1089/wound. 2014. 0581.
28. White WL, Brody GS, Glaser AA, Marangoni RD, Beckwith TG, Must JS, et al. Tensiometric studies of unwounded and wounded skin: results using a standardized testing method. Ann Surg 1971;173:19–25. https://doi. org/10. 1097/00000658-197101000-00003.
29. Corr DT, Gallant-Behm CL, Shrive NG, Hart DA. Biomechanical behavior of scar tissue and uninjured skin in a porcine model. Wound Repair Regen 2009;17:250–9. https://doi. org/10. 1111/j. 1524-475X. 2009. 00463. x.
30. Lim X, Tateya I, Tateya T, Muñoz-Del-Río A, Bless DM. Immediate inflammatory response and scar formation in wounded vocal folds. Ann Otol Rhinol Laryngol 2006;115:921–9. https://doi. org/10. 1177/000348940611501212.
31. Guo S, DiPietro LA. Factors Affecting Wound Healing. J Dent Res 2010;89:219–29. https://doi. org/10. 1177/0022034509359125.
32. Anderson K, Hamm RL. Factors That Impair Wound Healing. J Am Coll Clin Wound Spec 2014;4:84–91. https://doi. org/10. 1016/j. jccw. 2014. 03. 001.
33. Wilkinson HN, Hardman MJ. Wound healing: cellular mechanisms and pathological outcomes. Open Biol 2020;10:200223. https://doi. org/10. 1098/rsob. 200223.
34. Mirastschijski U, Sander JT, Zier U, Rennekampff HO, Weyand B, Vogt PM. The cost of post-burn scarring. Ann Burns Fire Disasters 2015;28:215–22.
35. Barnes LA, Marshall CD, Leavitt T, Hu MS, Moore AL, Gonzalez JG, et al. Mechanical Forces in Cutaneous Wound Healing: Emerging Therapies to Minimize Scar Formation. Adv Wound Care (New Rochelle) 2018;7:47–56. https://doi. org/10. 1089/wound. 2016. 0709.
36. Marshall CD, Hu MS, Leavitt T, Barnes LA, Lorenz HP, Longaker MT. Cutaneous Scarring: Basic Science, Current Treatments, and Future Directions. Adv Wound Care (New Rochelle) 2018;7:29–45. https://doi. org/10. 1089/wound. 2016. 0696.
37. van Zuijlen PPM, Ruurda JJB, van Veen HA, van Marle J, van Trier AJM, Groenevelt F, et al. Collagen morphology in human skin and scar tissue: no adaptations in response to mechanical loading at joints. Burns 2003;29:423–31. https://doi. org/10. 1016/s0305-4179(03)00052-4.
38. Kiani MT, Higgins CA, Almquist BD. The Hair Follicle: An Underutilized Source of Cells and Materials for Regenerative Medicine. ACS Biomater Sci Eng 2018;4:1193–207. https://doi. org/10. 1021/acsbiomaterials. 7b00072.
39. Fu X-B, Sun T-Z, Li X-K, Sheng Z-Y. Morphological and distribution characteristics of sweat glands in hypertrophic scar and their possible effects on sweat gland regeneration. Chin Med J (Engl) 2005;118:186–91.
40. Mulholland EJ. Electrospun Biomaterials in the Treatment and Prevention of Scars in Skin Wound Healing. Frontiers in Bioengineering and Biotechnology 2020;8.
41. Carswell L, Borger J. Hypertrophic Scarring Keloids. StatPearls, Treasure Island (FL): StatPearls Publishing; 2023.
42. Connolly D, Vu HL, Mariwalla K, Saedi N. Acne Scarring—Pathogenesis, Evaluation, and Treatment Options. J Clin Aesthet Dermatol 2017;10:12–23.
43. Boen M, Jacob C. A Review and Update of Treatment Options Using the Acne Scar Classification System. Dermatologic Surgery 2019;45:1. https://doi. org/10. 1097/DSS. 0000000000001765.
44. Jacob CI, Dover JS, Kaminer MS. Acne scarring: a classification system and review of treatment options. J Am Acad Dermatol 2001;45:109–17. https://doi. org/10. 1067/mjd. 2001. 113451.
45. Abdel Hay R, Shalaby K, Zaher H, Hafez V, Chi C-C, Dimitri S, et al. Interventions for acne scars. Cochrane Database Syst Rev 2016;4:CD011946. https://doi. org/10. 1002/14651858. CD011946. pub2.
46. Levy LL, Zeichner JA. Management of acne scarring, part II: a comparative review of non-laser-based, minimally invasive approaches. Am J Clin Dermatol 2012;13:331–40. https://doi. org/10. 2165/11631410-000000000-00000.
47. Barikbin B, Akbari Z, Yousefi M, Dowlati Y. Blunt Blade Subcision: An Evolution in the Treatment of Atrophic Acne Scars. Dermatol Surg 2017;43 Suppl 1:S57–63. https://doi. org/10. 1097/DSS. 0000000000000650.
48. Alam M, Han S, Pongprutthipan M, Disphanurat W, Kakar R, Nodzenski M, et al. Efficacy of a needling device for the treatment of acne scars: a randomized clinical trial. JAMA Dermatol 2014;150:844–9. https://doi. org/10. 1001/jamadermatol. 2013. 8687.
49. Cachafeiro T, Escobar G, Maldonado G, Cestari T, Corleta O. Comparison of Nonablative Fractional Erbium Laser 1,340 nm and Microneedling for the Treatment of Atrophic Acne Scars: A Randomized Clinical Trial. Dermatol Surg 2016;42:232–41. https://doi. org/10. 1097/DSS. 0000000000000597.
50. Callaghan DJ. Review on the treatment of scars. Plastic and Aesthetic Research 2020;7:66. https://doi. org/10. 20517/2347-9264. 2020. 166.
51. O’Brien L, Jones DJ. Silicone gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev 2013;2013:CD003826. https://doi. org/10. 1002/14651858. CD003826. pub3.
52. Morelli Coppola M, Salzillo R, Segreto F, Persichetti P. Triamcinolone acetonide intralesional injection for the treatment of keloid scars: patient selection and perspectives. Clin Cosmet Investig Dermatol 2018;11:387–96. https://doi. org/10. 2147/CCID. S133672.
53. Tidwell WJ, Owen CE, Kulp-Shorten C, Maity A, McCall M, Brown TS. Fractionated Er:YAG laser versus fully ablative Er:YAG laser for scar revision: Results of a split scar, double blinded, prospective trial. Lasers Surg Med 2016;48:837–43. https://doi. org/10. 1002/lsm. 22562.
54. Cohen JL. Minimizing skin cancer surgical scars using ablative fractional Er:YAG laser treatment. J Drugs Dermatol 2013;12:1171–3.
55. Gokalp H. Evaluation of nonablative fractional laser treatment in scar reduction. Lasers Med Sci 2017;32:1629–35. https://doi. org/10. 1007/s10103-017-2303-x.
56. González N, Goldberg DJ. Update on the Treatment of Scars. J Drugs Dermatol 2019;18:550–5.
57. Li K, Nicoli F, Cui C, Xi WJ, Al-Mousawi A, Zhang Z, et al. Treatment of hypertrophic scars and keloids using an intralesional 1470 nm bare-fibre diode laser: a novel efficient minimally-invasive technique. Sci Rep 2020;10:21694. https://doi. org/10. 1038/s41598-020-78738-9.
58. Mustoe TA, Cooter RD, Gold MH, Hobbs FDR, Ramelet A-A, Shakespeare PG, et al. International clinical recommendations on scar management. Plast Reconstr Surg 2002;110:560–71. https://doi. org/10. 1097/00006534-200208000-00031.
59. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med 2011;17:113–25. https://doi. org/10. 2119/molmed. 2009. 00153.
60. Monstrey S, Middelkoop E, Vranckx JJ, Bassetto F, Ziegler UE, Meaume S, et al. Updated scar management practical guidelines: non-invasive and invasive measures. J Plast Reconstr Aesthet Surg 2014;67:1017–25. https://doi. org/10. 1016/j. bjps. 2014. 04. 011.
61. Zouboulis CC. Cryosurgery in dermatology. Eur J Dermatol 1998;8:466–74.
62. Rabello FB, Souza CD, Júnior JAF. Update on hypertrophic scar treatment. Clinics (Sao Paulo) 2014;69:565–73. https://doi. org/10. 6061/clinics/2014(08)11.
63. Shaffer JJ, Taylor SC, Cook-Bolden F. Keloidal scars: a review with a critical look at therapeutic options. J Am Acad Dermatol 2002;46:S63-97. https://doi. org/10. 1067/mjd. 2002. 120788.
64. Hession MT, Graber EM. Atrophic Acne Scarring. J Clin Aesthet Dermatol 2015;8:50–8.
65. Magnani LR, Schweiger ES. Fractional CO2 lasers for the treatment of atrophic acne scars: a review of the literature. J Cosmet Laser Ther 2014;16:48–56. https://doi. org/10. 3109/14764172. 2013. 854639.
66. Senthil T, Anandhan S. Fabrication of styrene–acrylonitrile random copolymer nanofiber membranes from N,N-dimethyl formamide by electrospinning. Journal of Elastomers & Plastics 2015;47:327–46. https://doi. org/10. 1177/0095244313514987.
67. Sharma GK, James NR, Sharma GK, James NR. Electrospinning: The Technique and Applications. Recent Developments in Nanofibers Research, IntechOpen; 2022. https://doi. org/10. 5772/intechopen. 105804.
68. Kalaoglu-Altan OI, Baskan H, Meireman T, Basnett P, Azimi B, Fusco A, et al. Silver Nanoparticle-Coated Polyhydroxyalkanoate Based Electrospun Fibers for Wound Dressing Applications. Materials (Basel) 2021;14:4907. https://doi. org/10. 3390/ma14174907.
69. Wang C, Wang J, Zeng L, Qiao Z, Liu X, Liu H, et al. Fabrication of Electrospun Polymer Nanofibers with Diverse Morphologies. Molecules 2019;24:834. https://doi. org/10. 3390/molecules24050834.
70. Xie J, Macewan M, Schwartz A, Xia Y. Electrospun nanofibers for neural tissue engineering. Nanoscale 2010;2:35–44. https://doi. org/10. 1039/b9nr00243j.
71. Xue J, Wu T, Dai Y, Xia Y. Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications. Chem Rev 2019;119:5298–415. https://doi. org/10. 1021/acs. chemrev. 8b00593.
72. Ahmadi Bonakdar M, Rodrigue D. Electrospinning: Processes, Structures, and Materials. Macromol 2024;4:58–103. https://doi. org/10. 3390/macromol4010004.
73. Moghe A, Gupta B. Co‐axial Electrospinning for Nanofiber Structures: Preparation and Applications. Polymer Reviews - POLYM REV 2008;48:353–77. https://doi. org/10. 1080/15583720802022257.
74. Khan J, Khan A, Khan MQ, Khan H. Applications of co-axial electrospinning in the biomedical field. Next Materials 2024;3:100138. https://doi. org/10. 1016/j. nxmate. 2024. 100138.
75. Wei Q, Xu F, Xu X, Geng X, Ye L, Zhang A, et al. The multifunctional wound dressing with core–shell structured fibers prepared by coaxial electrospinning. Front Mater Sci 2016;10:113–21. https://doi. org/10. 1007/s11706-016-0339-7.
76. He H, Wu M, Zhu J, Yang Y, Ge R, Yu D. Engineered Spindles of Little Molecules Around Electrospun Nanofibers for Biphasic Drug Release. Advanced Fiber Materials 2021;4. https://doi. org/10. 1007/s42765-021-00112-9.
77. Abadi B, Goshtasbi N, Bolourian S, Tahsili J, Adeli-Sardou M, Forootanfar H. Electrospun hybrid nanofibers: Fabrication, characterization, and biomedical applications. Front Bioeng Biotechnol 2022;10:986975. https://doi. org/10. 3389/fbioe. 2022. 986975.
78. Li F, Zhao Y, Song Y, Li F, Zhao Y, Song Y. Core-Shell Nanofibers: Nano Channel and Capsule by Coaxial Electrospinning. Nanofibers, IntechOpen; 2010. https://doi. org/10. 5772/8166.
79. Al-Abduljabbar A, Farooq I. Electrospun Polymer Nanofibers: Processing, Properties, and Applications. Polymers 2023;15:65. https://doi. org/10. 3390/polym15010065.
80. Bachs-Herrera A, Yousefzade O, del Valle LJ, Puiggali J. Melt Electrospinning of Polymers: Blends, Nanocomposites, Additives and Applications. Applied Sciences 2021;11:1808. https://doi. org/10. 3390/app11041808.
81. Xu H, Yamamoto M, Yamane H. Melt electrospinning: Electrodynamics and spinnability. Polymer 2017;132. https://doi. org/10. 1016/j. polymer. 2017. 11. 006.
82. Zhang C, Feng F, ZHANG H. Emulsion electrospinning: Fundamentals, food applications and prospects. Trends in Food Science & Technology 2018;80. https://doi. org/10. 1016/j. tifs. 2018. 08. 005.
83. Nikmaram N, Roohinejad S, Hashemi S, Koubaa M, J. Barba F, Abbaspourrad A, et al. Emulsion-based systems for fabrication of electrospun nanofibers: food, pharmaceutical and biomedical applications. RSC Advances 2017;7:28951–64. https://doi. org/10. 1039/C7RA00179G.
84. CeCe R, Jining L, Islam M, Korvink JG, Sharma B. An Overview of the Electrospinning of Polymeric Nanofibers for Biomedical Applications Related to Drug Delivery. Advanced Engineering Materials 2024;26:2301297. https://doi. org/10. 1002/adem. 202301297.
85. Salas C. Solution electrospinning of nanofibers, 2017, p. 73–108. https://doi. org/10. 1016/B978-0-08-100907-9. 00004-0.
86. Alghoraibi I, Alomari S. Different Methods for Nanofiber Design and Fabrication. In: Barhoum A, Bechelany M, Makhlouf A, editors. Handbook of Nanofibers, Cham: Springer International Publishing; 2018, p. 1–46. https://doi. org/10. 1007/978-3-319-42789-8_11-2.
87. Aderibigbe BA, Buyana B. Alginate in Wound Dressings. Pharmaceutics 2018;10:42. https://doi. org/10. 3390/pharmaceutics10020042.
88. Nie H, He A, Zheng J, Xu S, Li J, Han CC. Effects of Chain Conformation and Entanglement on the Electrospinning of Pure Alginate. Biomacromolecules 2008;9:1362–5. https://doi. org/10. 1021/bm701349j.
89. Tören E, Mazari A. Needless electrospun collagen/hyaluronic acid nanofibers for skin moisturization: Research. Polymers for Advanced Technologies 2024;35. https://doi. org/10. 1002/pat. 6434.
90. Nallathambi G. Calcium alginate/PVA blended nano fibre matrix for wound dressing. Indian Journal of Fibre and Textile Research 2012;37:127–32.
91. Field CK, Kerstein MD. Overview of wound healing in a moist environment. The American Journal of Surgery 1994;167:S2–6. https://doi. org/10. 1016/0002-9610(94)90002-7.
92. Ignatova M, Starbova K, Markova N, Manolova N, Rashkov I. Electrospun nano-fibre mats with antibacterial properties from quaternised chitosan and poly(vinyl alcohol). Carbohydrate Research 2006;341:2098–107. https://doi. org/10. 1016/j. carres. 2006. 05. 006.
93. Shete AS, Yadav AV, Murthy SM. Chitosan and chitosan chlorhydrate based various approaches for enhancement of dissolution rate of carvedilol. DARU J Pharm Sci 2012;20:93. https://doi. org/10. 1186/2008-2231-20-93.
94. Gu X, Li Y, Cao R, Liu S, Fu C, Feng S, et al. Novel electrospun poly(lactic acid)/poly(butylene carbonate)/graphene oxide nanofiber membranes for antibacterial applications. AIP Advances 2019;9:065315. https://doi. org/10. 1063/1. 5100109.
95. Ju HW, Lee OJ, Lee JM, Moon BM, Park HJ, Park YR, et al. Wound healing effect of electrospun silk fibroin nanomatrix in burn-model. Int J Biol Macromol 2016;85:29–39. https://doi. org/10. 1016/j. ijbiomac. 2015. 12. 055.
96. Zhou T, Wang N, Xue Y, Ding T, Liu X, Mo X, et al. Electrospun tilapia collagen nanofibers accelerating wound healing via inducing keratinocytes proliferation and differentiation. Colloids and Surfaces B: Biointerfaces 2016;143:415–22. https://doi. org/10. 1016/j. colsurfb. 2016. 03. 052.
97. Pal P, Dadhich P, Srivas PK, Das B, Maulik D, Dhara S. Bilayered nanofibrous 3D hierarchy as skin rudiment by emulsion electrospinning for burn wound management. Biomater Sci 2017;5:1786–99. https://doi. org/10. 1039/C7BM00174F.
98. Kellar RS, Diller RB, Tabor AJ, Dominguez DD, Audet RG, Bardsley TA, et al. Improved Wound Closure Rates and Mechanical Properties Resembling Native Skin in Murine Diabetic Wounds Treated with a Tropoelastin and Collagen Wound Healing Device. J Diabetes Clin Res 2020;Volume 2:86–99. https://doi. org/10. 33696/diabetes. 1. 024.
99. Zhang K, Bai X, Yuan Z, Cao X, Jiao X, Li Y, et al. Layered nanofiber sponge with an improved capacity for promoting blood coagulation and wound healing. Biomaterials 2019;204:70–9. https://doi. org/10. 1016/j. biomaterials. 2019. 03. 008.
100. Xie B, Zhu W, Ding P, Chen M, Li J, Lei L, et al. Nanofiber scaffolds attenuate collagen synthesis of human dermal fibroblasts through TGF-β1/TSG-6 pathway*. J Phys Mater 2019;2:044001. https://doi. org/10. 1088/2515-7639/ab2563.
101. Yu H, Chen X, Cai J, Ye D, Wu Y, Fan L, et al. Novel porous three-dimensional nanofibrous scaffolds for accelerating wound healing. Chemical Engineering Journal 2019;369:253–62. https://doi. org/10. 1016/j. cej. 2019. 03. 091.
102. Kim HN, Hong Y, Kim MS, Kim SM, Suh K-Y. Effect of orientation and density of nanotopography in dermal wound healing. Biomaterials 2012;33:8782–92. https://doi. org/10. 1016/j. biomaterials. 2012. 08. 038.
103. Sun L, Gao W, Fu X, Shi M, Xie W, Zhang W, et al. Enhanced wound healing in diabetic rats by nanofibrous scaffolds mimicking the basketweave pattern of collagen fibrils in native skin. Biomater Sci 2018;6:340–9. https://doi. org/10. 1039/C7BM00545H.
104. Dubský M, Kubinová Š, Širc J, Voska L, Zajíček R, Zajícová A, et al. Nanofibers prepared by needleless electrospinning technology as scaffolds for wound healing. J Mater Sci: Mater Med 2012;23:931–41. https://doi. org/10. 1007/s10856-012-4577-7.
105. Chantre CO, Campbell PH, Golecki HM, Buganza AT, Capulli AK, Deravi LF, et al. Production-scale fibronectin nanofibers promote wound closure and tissue repair in a dermal mouse model. Biomaterials 2018;166:96–108. https://doi. org/10. 1016/j. biomaterials. 2018. 03. 006.
106. Hsu F-Y, Hung Y-S, Liou H-M, Shen C-H. Electrospun hyaluronate–collagen nanofibrous matrix and the effects of varying the concentration of hyaluronate on the characteristics of foreskin fibroblast cells. Acta Biomaterialia 2010;6:2140–7. https://doi. org/10. 1016/j. actbio. 2009. 12. 023.
107. Chen J-P, Chang G-Y, Chen J-K. Electrospun collagen/chitosan nanofibrous membrane as wound dressing. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2008;313–314:183–8. https://doi. org/10. 1016/j. colsurfa. 2007. 04. 129.
108. Choi JS, Leong KW, Yoo HS. In vivo wound healing of diabetic ulcers using electrospun nanofibers immobilized with human epidermal growth factor (EGF). Biomaterials 2008;29:587–96. https://doi. org/10. 1016/j. biomaterials. 2007. 10. 012.
109. Choi JS, Choi SH, Yoo HS. Coaxial electrospun nanofibers for treatment of diabetic ulcers with binary release of multiple growth factors. J Mater Chem 2011;21:5258–67. https://doi. org/10. 1039/C0JM03706K.
110. Garcia-Orue I, Gainza G, Gutierrez FB, Aguirre JJ, Evora C, Pedraz JL, et al. Novel nanofibrous dressings containing rhEGF and Aloe vera for wound healing applications. International Journal of Pharmaceutics 2017;523:556–66. https://doi. org/10. 1016/j. ijpharm. 2016. 11. 006.
111. Lai H-J, Kuan C-H, Wu H-C, Tsai J-C, Chen T-M, Hsieh D-J, et al. Tailored design of electrospun composite nanofibers with staged release of multiple angiogenic growth factors for chronic wound healing. Acta Biomaterialia 2014;10:4156–66. https://doi. org/10. 1016/j. actbio. 2014. 05. 001.
112. Xie Z, Paras CB, Weng H, Punnakitikashem P, Su L-C, Vu K, et al. Dual growth factor releasing multi-functional nanofibers for wound healing. Acta Biomaterialia 2013;9:9351–9. https://doi. org/10. 1016/j. actbio. 2013. 07. 030.
113. Yuan Z, Zhao J, Chen Y, Yang Z, Cui W, Zheng Q. Regulating Inflammation Using Acid-Responsive Electrospun Fibrous Scaffolds for Skin Scarless Healing. Mediators of Inflammation 2014;2014:858045. https://doi. org/10. 1155/2014/858045.
114. Mohiti-Asli M, Saha S, Murphy S v. , Gracz H, Pourdeyhimi B, Atala A, et al. Ibuprofen loaded PLA nanofibrous scaffolds increase proliferation of human skin cells in vitro and promote healing of full thickness incision wounds in vivo. Journal of Biomedical Materials Research Part B: Applied Biomaterials 2017;105:327–39. https://doi. org/10. 1002/jbm. b. 33520.
115. Ren X, Han Y, Wang J, Jiang Y, Yi Z, Xu H, et al. An aligned porous electrospun fibrous membrane with controlled drug delivery – An efficient strategy to accelerate diabetic wound healing with improved angiogenesis. Acta Biomaterialia 2018;70:140–53. https://doi. org/10. 1016/j. actbio. 2018. 02. 010.
116. Liu X, Lin T, Gao Y, Xu Z, Huang C, Yao G, et al. Antimicrobial electrospun nanofibers of cellulose acetate and polyester urethane composite for wound dressing. Journal of Biomedical Materials Research Part B: Applied Biomaterials 2012;100B:1556–65. https://doi. org/10. 1002/jbm. b. 32724.
117. Poormasjedi-Meibod M-S, Salimi Elizei S, Leung V, Baradar Jalili R, Ko F, Ghahary A. Kynurenine Modulates MMP-1 and Type-I Collagen Expression Via Aryl Hydrocarbon Receptor Activation in Dermal Fibroblasts. Journal of Cellular Physiology 2016;231:2749–60. https://doi. org/10. 1002/jcp. 25383.
118. Vargas EAT, do Vale Baracho NC, de Brito J, de Queiroz AAA. Hyperbranched polyglycerol electrospun nanofibers for wound dressing applications. Acta Biomaterialia 2010;6:1069–78. https://doi. org/10. 1016/j. actbio. 2009. 09. 018.
119. Jung S-M, Min SK, Lee HC, Kwon YS, Jung MH, Shin HS. Spirulina-PCL Nanofiber Wound Dressing to Improve Cutaneous Wound Healing by Enhancing Antioxidative Mechanism. Journal of Nanomaterials 2016;2016:6135727. https://doi. org/10. 1155/2016/6135727.
120. Tören E, Mazari A, Buzgo M. Exploring the efficacy of AHA–BHA infused nanofiber skin masks as a topical treatment for acne vulgaris. Journal of Applied Polymer Science 2024;141. https://doi. org/10. 1002/app. 55203.
121. Paiva-Santos AC, Mascarenhas-Melo F, Coimbra SC, Pawar KD, Peixoto D, Chá-Chá R, et al. Nanotechnology-based formulations toward the improved topical delivery of anti-acne active ingredients. Expert Opinion on Drug Delivery 2021;18:1435–54. https://doi. org/10. 1080/17425247. 2021. 1951218.
122. Lin T-K, Zhong L, Santiago JL. Anti-Inflammatory and Skin Barrier Repair Effects of Topical Application of Some Plant Oils. Int J Mol Sci 2017;19:70. https://doi. org/10. 3390/ijms19010070.
123. Crucho CIC, Barros MT. Polymeric nanoparticles: A study on the preparation variables and characterization methods. Materials Science and Engineering: C 2017;80:771–84. https://doi. org/10. 1016/j. msec. 2017. 06. 004.
124. Mauricio MD, Guerra-Ojeda S, Marchio P, Valles SL, Aldasoro M, Escribano-Lopez I, et al. Nanoparticles in Medicine: A Focus on Vascular Oxidative Stress. Oxidative Medicine and Cellular Longevity 2018;2018:e6231482. https://doi. org/10. 1155/2018/6231482.
125. Kushwaha A, Goswami L, Kim BS. Nanomaterial-Based Therapy for Wound Healing. Nanomaterials 2022;12:618. https://doi. org/10. 3390/nano12040618.
126. Fahmy HM, Salah Eldin RE, Abu Serea ES, Gomaa NM, AboElmagd GM, Salem SA, et al. Advances in nanotechnology and antibacterial properties of biodegradable food packaging materials. RSC Adv 2020;10:20467–84. https://doi. org/10. 1039/D0RA02922J.
127. Kolanthai E, Fu Y, Kumar U, Babu B, Venkatesan AK, Liechty KW, et al. Nanoparticle mediated RNA delivery for wound healing. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2022;14:e1741. https://doi. org/10. 1002/wnan. 1741.
128. Rashki S, Asgarpour K, Tarrahimofrad H, Hashemipour M, Ebrahimi MS, Fathizadeh H, et al. Chitosan-based nanoparticles against bacterial infections. Carbohydr Polym 2021;251:117108. https://doi. org/10. 1016/j. carbpol. 2020. 117108.
129. Suamte L, Babu PJ. Electrospun based functional scaffolds for biomedical engineering: A review. Nano TransMed 2024:100055. https://doi. org/10. 1016/j. ntm. 2024. 100055.
130. Tören E, Mazari A. Pullulan/Collagen Scaffolds Promote Chronic Wound Healing via Mesenchymal Stem Cells. Micro 2024;4. https://doi. org/10. 3390/micro4040037.
131. Burdick JA, Mauck RL, Gerecht S. To Serve and Protect: Hydrogels to Improve Stem Cell-Based Therapies. Cell Stem Cell 2016;18:13–5. https://doi. org/10. 1016/j. stem. 2015. 12. 004.
132. Li Z, Wang H, Yang B, Sun Y, Huo R. Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring. Materials Science and Engineering: C 2015;57:181–8. https://doi. org/10. 1016/j. msec. 2015. 07. 062.
133. Hornos Carneiro MF, Barbosa F. Gold nanoparticles: A critical review of therapeutic applications and toxicological aspects. J Toxicol Environ Health B Crit Rev 2016;19:129–48. https://doi. org/10. 1080/10937404. 2016. 1168762.
134. Kumar M, Kulkarni P, Liu S, Chemuturi N, Shah DK. Nanoparticle biodistribution coefficients: A quantitative approach for understanding the tissue distribution of nanoparticles. Adv Drug Deliv Rev 2023;194:114708. https://doi. org/10. 1016/j. addr. 2023. 114708.
135. Mohammapdour R, Ghandehari H. Mechanisms of immune response to inorganic nanoparticles and their degradation products. Adv Drug Deliv Rev 2022;180:114022. https://doi. org/10. 1016/j. addr. 2021. 114022.
136. Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. Small 2008;4:26–49. https://doi. org/10. 1002/smll. 200700595.
137. Balfourier A, Luciani N, Wang G, Lelong G, Ersen O, Khelfa A, et al. Unexpected intracellular biodegradation and recrystallization of gold nanoparticles. Proc Natl Acad Sci U S A 2020;117:103–13. https://doi. org/10. 1073/pnas. 1911734116.
138. Hasan A, Morshed M, Memic A, Hassan S, Webster TJ, Marei HE-S. Nanoparticles in tissue engineering: applications, challenges and prospects. Int J Nanomedicine 2018;13:5637–55. https://doi. org/10. 2147/IJN. S153758.
139. Maurer-Jones MA, Bantz KC, Love SA, Marquis BJ, Haynes CL. Toxicity of therapeutic nanoparticles. Nanomedicine (Lond) 2009;4:219–41. https://doi. org/10. 2217/17435889. 4. 2. 219.