Exosomes As A Revolutionary Tool In Wound Healing And Skin Regeneration: Current Evidence And Therapeutic Potential
Keywords:
Exosomes, wound healing, skin regeneration, nanoscale vesicles, intercellular communication, bioactive cargo, miRNAs, chronic wounds, burns, aesthetic dermatology, exosome-derived biomaterials, hydrogels, engineered exosomes, targeted delivery, plant-deriAbstract
Nano-sized extracellular vesicles, such as the exosomes, innovate wound healing and skin regeneration based on intercellular crosstalk via bioactive payloads (miRNA, proteins, lipids). This review outlines the ability of these compounds to accelerate wound healing, mitigate inflammation, and promote tissue remodeling, as well as recent findings from preclinical and clinical trials. Discoveries, such as exosome-derived biomaterials, including hydrogels, and targeted delivery systems, like CRISPR-engineered exosomes, enhance the efficacy of therapeutics. The existence of rare and exciting discoveries validates the future of transformative possibilities, including hypoxic-conditioned exosomes that stimulate HIF-1α and plant exosomes that enhance burn healing, such as those derived from ginger. Preliminary data indicate that mesenchymal stem cell-derived exosomes can improve healing rates by up to 30-50% in diabetic models, and early-phase clinical studies suggest a decrease in scarring and chronic wound inflammation in chronic wounds. Exosomes have significant clinical and translational potential in the treatment of chronic wounds, burns, and aesthetic dermatology, meeting the demand for biocompatible, low-immunogenicity products. These advances make exosomes a transformative type of regenerative medicine, marking a breakthrough in personalized and scalable applications of wound care and skin regeneration despite the challenges of scalability and standardization.
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Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H., & Tomic-Canic, M. (2008). Growth factors and cytokines in wound healing. Wound Repair and Regeneration, 16(5), 585–601. https://doi.org/10.1111/j.1524-475X.2008.00410.x
BioRender. (2024). Wound healing process illustration. Retrieved from https://www.biorender.com
ClinicalTrials.gov. (2025). Exosome-based therapies for chronic wound healing. https://clinicaltrials.gov/
Dang, E., Man, G., Lee, D., Cheung, C., Elias, P. M., & Man, M. (2016). Inducible nitric oxide synthase is crucial for epidermal permeability barrier homeostasis. Journal of Investigative Dermatology, 136(5), S55. https://doi.org/10.1016/j.jid.2016.02.333
Falanga, V. (2005). Wound healing and its impairment in the diabetic foot. The Lancet, 366(9498), 1736–1743. https://doi.org/10.1016/S0140-6736(05)67700-8
Fang, S., Xu, C., Zhang, Y., Xue, C., Yang, C., Bi, H., ... & Zhang, X. (2016). Umbilical cord-derived mesenchymal stem cell-derived exosomal microRNAs suppress myofibroblast differentiation. Stem Cells Translational Medicine, 5(10), 1425–1434. https://doi.org/10.5966/sctm.2015-0365
Gurtner, G. C., Werner, S., Barrandon, Y., & Longaker, M. T. (2008). Wound repair and regeneration. Nature, 453(7193), 314–321. https://doi.org/10.1038/nature07039
Hessvik, N. P., & Llorente, A. (2018). Current knowledge on exosome biogenesis and release. Cellular and Molecular Life Sciences, 75(2), 193–208. https://doi.org/10.1007/s00018-017-2595-9
Hu, L., Wang, J., Zhou, X., Xiong, Z., Zhao, J., Yu, R., ... & Zhang, Y. (2018). Exosomes derived from human adipose mesenchymal stem cells accelerate cutaneous wound healing via optimizing fibroblast functions. Stem Cell Research & Therapy, 9(1), 217. https://doi.org/10.1186/s13287-018-0969-y
Jang, S. C., Kim, O. Y., Yoon, C. M., Choi, D. S., Roh, T. Y., Park, J., ... & Gho, Y. S. (2013). Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano, 7(9), 7698–7710. https://doi.org/10.1021/nn402232g
Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367(6478), Article eaau6977. https://doi.org/10.1126/science.aau6977
Li, S., Zhao, Y., Lyu, X., Chen, Y., Zhang, T., Lin, S., ... & Lin, Y. (2025). Enzyme-responsive nanoparachute for targeted miRNA delivery: A protective strategy against acute liver and kidney injury. Advanced Science, 12(10), Article 2411210. https://doi.org/10.1002/advs.202411210
Liu, C., Cheng, C., Cheng, K., Gao, A. S., Li, Q., Atala, A., & Zhang, Y. (2025). Precision exosome engineering for enhanced wound healing and scar revision. Journal of Translational Medicine, 23(1), 1-30.
Liang, Z. H., Pan, Y. C., Lin, S. S., Qiu, Z. Y., & Zhang, Z. (2020). LncRNA MALAT1 promotes wound healing via regulating miR-141-3p/ZNF217 axis. Regenerative Therapy, 15, 202–209. https://doi.org/10.1016/j.reth.2020.09.006
Pittenger, M. F., Discher, D. E., Péault, B. M., Phinney, D. G., Hare, J. M., & Caplan, A. I. (2019). Mesenchymal stem cell perspective: Cell biology to clinical progress. NPJ Regenerative Medicine, 4, Article 22. https://doi.org/10.1038/s41536-019-0083-6
Riazifar, M., Pone, E. J., Lötvall, J., & Zhao, W. (2017). Stem cell extracellular vesicles: Extended messages of regeneration. Annual Review of Pharmacology and Toxicology, 57, 125–154. https://doi.org/10.1146/annurev-pharmtox-061616-011544
Shabbir, A., Cox, A., Rodriguez-Menocal, L., Salgado, M., & Badiavas, E. V. (2015). Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro. Stem Cells and Development, 24(14), 1635–1647. https://doi.org/10.1089/scd.2014.0316
Singer, A. J., & Clark, R. A. F. (1999). Cutaneous wound healing. New England Journal of Medicine, 341(10), 738–746. https://doi.org/10.1056/NEJM199909023411006
Skotland, T., Sandvig, K., & Llorente, A. (2017). Lipids in exosomes: Current knowledge and the way forward. Progress in Lipid Research, 66, 30–41. https://doi.org/10.1016/j.plipres.2017.03.001
Tao, S.-C., Guo, S.-C., & Zhang, C.-Q. (2018). Modularized extracellular vesicles: The dawn of prospective personalized and precision medicine. Advanced Science, 5(2), Article 1700449. https://doi.org/10.1002/advs.201700449
Théry, C., Witwer, K. W., Aikawa, E., & Alcaraz, M. J. (2018). Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles. Journal of Extracellular Vesicles, 7(1), Article 1535750. https://doi.org/10.1080/20013078.2018.1535750
Ti, D., Hao, H., Fu, X., & Han, W. (2016). Mesenchymal stem cells-derived exosomal microRNAs contribute to wound inflammation. Science China Life Sciences, 59(12), 1305–1312. https://doi.org/10.1007/s11427-016-0240-4
Trajkovic, K., Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., ... & Simons, M. (2008). Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 319(5867), 1244–1247. https://doi.org/10.1126/science.1153124
Tredget, E. E., Nedelec, B., Scott, P. G., & Ghahary, A. (1997). Hypertrophic scars, keloids, and contractures: The cellular and molecular basis for therapy. Surgical Clinics of North America, 77(3), 701–730. https://doi.org/10.1016/S0039-6109(05)70576-4
Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology, 9(6), 654–659. https://doi.org/10.1038/ncb1596
Zhang, J., Chen, C., Hu, B., Niu, X., Liu, X., Zhang, G., ... & Wang, Y. (2016). Exosomes derived from human endothelial progenitor cells accelerate cutaneous wound healing by promoting angiogenesis through Erk1/2 signaling. International Journal of Biological Sciences, 12(12), 1472–1487. https://doi.org/10.7150/ijbs.15514
Zhang, M., Viennois, E., Prasad, M., Zhang, Y., Wang, L., Zhang, Z., ... & Merlin, D. (2016). Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials, 101, 321–340. https://doi.org/10.1016/j.biomaterials.2016.06.018
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