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Scientific Reports , Article number: (2026) Cite this article
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Abstract
Exosomes are rapidly emerging as a novel field in wound healing. Wound healing is a complex phenomenon characterized by a series of dynamic physiological functions. Despite the promising benefits of using exosomes for wound healing, many challenges remain to be addressed. Advances in nanotechnology and regenerative medicine have led to the development of hybrid systems that combine the advantageous properties of exosomes and nanoparticles, significantly enhancing wound healing outcomes. In this study, exosomes were isolated from human Adipose-Derived Stem Cells (ADSCs). Layered double hydroxide (LDH) was synthesized, and LDH/Exosome (LDH/Exo) nanohybrids were prepared. Following the successful characterization of exosomes, the LDH/Exo nanohybrid was assessed using field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), and energy-dispersive X-ray spectroscopy (EDX). Our results showed that the LDH enabled the sustained release of the exosomes, especially during the early stage. Cell viability and scratch assay analyses were performed to evaluate the potential of LDH/Exo nanohybrid systems in wound healing. Also, a dose-dependent reduction in bacterial growth indicated the antimicrobial activity. The results demonstrated that the chemical structures and morphology of exosomes remained intact. Additionally, the LDH/Exo nanohybrids showed no cytotoxic effects on the L929 mouse fibroblast cell line. The highest rate of wound closure was achieved in the LDH/Exo (100 and 125 µg) groups. This paper, for the first time, explores the potential of LDH/Exosome nanohybrid systems in wound healing.
Data availability
The datasets generated during the current study are available from the corresponding author on reasonable request.
References
-
Kalluri, R. The biology and function of exosomes in cancer. J. Clin. Investig. 126 (4), 1208–1215 (2016).
-
Prasai, A. et al. Role of exosomes in dermal wound healing: a systematic review. J. Invest. Dermatology. 142 (3), 662–678 (2022). e8.
-
He, X. et al. MSC-derived exosome promotes M2 polarization and enhances cutaneous wound healing. Stem Cells Int. 2019 (1), 7132708 (2019).
-
Lu, S. et al. Native and engineered extracellular vesicles for wound healing. Front. Bioeng. Biotechnol. 10, 1053217 (2022).
-
Fu, S. et al. Exosome engineering: current progress in cargo loading and targeted delivery. NanoImpact 20, 100261 (2020).
-
Wallace, H. A., Basehore, B. M. & Zito, P. M. Wound Healing Phases (2017).
-
Akita, S. Wound repair and regeneration: mechanisms, signaling. MDPI. p. 6328. (2019).
-
Xin, H., Li, Y. & Chopp, M. Exosomes/miRNAs as mediating cell-based therapy of stroke. Front. Cell. Neurosci. 8, 377 (2014).
-
Lv, H. et al. Exosome derived from stem cell: A promising therapeutic for wound healing. Front. Pharmacol. 13, 957771 (2022).
-
Sousa, P. et al. Advancements and insights in exosome-based therapies for wound healing: a comprehensive systematic review (2018–June 2023). Biomedicines 11 (8), p2099 (2023).
-
Gowda, B. et al. Nanoparticle-based therapeutic approaches for wound healing: A review of the state-of-the-art. Mater. Today Chem. 27, 101319 (2023).
-
Esfanjani, E. et al. Electrospun Polycaprolactone coated with gum tragacanth containing layered double hydroxide/thymol nanohybrid for wound dressing application. Int. J. Biol. Macromol. 309, 143049 (2025).
-
Fernandes, J. C. Layered double hydroxides are promising nanomaterials for tissue bioengineering applications. Adv. Biosystems. 3 (7), 1800238 (2019).
-
Szerlauth, A. et al. Reduction of intracellular oxidative stress with a copper-incorporated layered double hydroxide. Chem. Commun. 60 (10), 1325–1328 (2024).
-
Marugan, E. et al. Allantoin–zinc layered simple hydroxide biohybrid as antimicrobial active phase in cellulosic bionanocomposites as potential wound dressings. Appl. Clay Sci. 241, 107002 (2023).
-
Zhang, W. et al. Gelatin-Based hydrogel functionalized with dopamine and layered double hydroxide for wound healing. Gels 10 (5), 318 (2024).
-
An, Y. et al. Exosomes from adipose-derived stem cells and application to skin wound healing. Cell Prolif. 54 (3), e12993 (2021).
-
Yu, H. et al. Exosomes derived from E2F1–/–adipose-derived stem cells promote skin wound healing via miR-130b-5p/TGFBR3 axis. Int. J. Nanomed., : pp. 6275–6292. (2023).
-
Wang, Y. et al. Exosomes from adipose-derived stem cells accelerate wound healing by increasing the release of IL-33 from macrophages. Stem Cell Res. Ther. 16 (1), 80 (2025).
-
Shafiei, S. et al. Synthesis and characterisation of nanocrystalline Ca–Al layered double hydroxide {[Ca2Al (OH) 6] NO3. nH2O}: in vitro study. Adv. Appl. Ceram. 112 (1), 59–65 (2013).
-
Enderami, S. E. et al. Evaluation of osteogenic differentiation of bone marrow-derived mesenchymal stem cell on highly porous Polycaprolactone scaffold reinforced with layered double hydroxides nanoclay. Front. Bioeng. Biotechnol. 10, 805969 (2022).
-
Wong, L. W. et al. The convergence of FTIR and evs: emergence strategy for non-invasive cancer markers discovery. Diagnostics 13 (1), 22 (2022).
-
Stępień, E. et al. Fourier-Transform infrared (FT-IR) spectroscopy to show alterations in molecular composition of EV subpopulations from melanoma cell lines in different malignancies. Biochem. Biophys. Rep. 25, 100888 (2021).
-
Ridolfi, A. et al. AFM-based high-throughput Nanomechanical screening of single extracellular vesicles. Anal. Chem. 92 (15), 10274–10282 (2020).
-
Dai, W. et al. Microenvironmental cue-regulated exosomes as therapeutic strategies for improving chronic wound healing. NPG Asia Mater. 14 (1), 75 (2022).
-
Zhang, J. et al. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway. Stem Cell Res. Ther. 7, 1–14 (2016).
-
Rasti, M. et al. Enhancing the wound healing process through local injection of exosomes derived from blood serum: an in vitro and in vivo assessment. Regenerative Therapy. 26, 281–289 (2024).
-
Umapathi, A., Kumawat, M. & Daima, H. K. Engineered nanomaterials for biomedical applications and their toxicity: a review. Environ. Chem. Lett. 20 (1), 445–468 (2022).
-
Etheridge, M. L. et al. The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomed. Nanotechnol. Biol. Med. 9 (1), 1–14 (2013).
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Shavandi, M., Shafiei, S.S. & Salimi, M. Exosome-based layered double hydroxide nanohybrids from adipose-derived stem cells enhance dermal wound healing. Sci Rep (2026). https://doi.org/10.1038/s41598-025-34937-w
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DOI: https://doi.org/10.1038/s41598-025-34937-w
