BOTULINUM TOXIN TYPE A IN SCAR MODULATION: PREVENTION AND TREATMENT OF HYPERTROPHIC SCARS AND KELOID

Aleksandra Kujach; Julia Góralska; Melania Popielarczyk; Katarzyna Napiórkowska; Dominik Płaza

doi:10.31435/ijitss.2(50).2026.6138

Authors

Aleksandra Kujach M.D., University Clinical Centre, Gdańsk, Poland https://orcid.org/0009-0004-8338-136X
Julia Góralska Medical University of Gdańsk, Gdańsk, Poland https://orcid.org/0009-0004-7594-0387
Melania Popielarczyk Medical University of Gdańsk, Gdańsk, Poland https://orcid.org/0009-0000-0658-069X
Katarzyna Napiórkowska M.D., Nicolaus Copernicus Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0002-9736-9252
Dominik Płaza Scientific Circle of Neurotraumatology, Department of Emergency Medicine, Medical University of Gdańsk, Gdańsk, Poland https://orcid.org/0009-0000-6251-3969

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.6138

Keywords:

Botulinum Toxin Type A; Hypertrophic Scar; Keloid; Scar Prevention; Neurogenic Inflammation; Macrophage Polarization; Intralesional Therapy

Abstract

Hypertrophic scars and keloids are fibroproliferative disorders of the dermis that arise from dysregulated wound healing and are characterized by excessive extracellular matrix deposition, persistent inflammation, fibroblast activation, and variable recurrence after treatment. Despite the availability of silicone therapy, pressure therapy, corticosteroids, 5-fluorouracil, bleomycin, lasers, cryotherapy, surgery, and radiotherapy, no universally effective treatment algorithm has been established. Botulinum toxin type A (BoNT-A) has emerged as a promising scar-modulating agent with potential value in both early postoperative scar prevention and treatment of established hypertrophic scars and keloids. Initially, its effect was attributed mainly to chemodenervation and reduction of mechanical tension across wound edges. However, accumulating experimental and clinical evidence suggests broader mechanisms, including modulation of fibroblast proliferation, suppression of transforming growth factor-β/connective tissue growth factor signaling, reduction of α-smooth muscle actin and collagen I/III expression, interference with neurogenic inflammation through the substance P–neurokinin-1 receptor pathway, regulation of macrophage polarization, and effects on intracellular profibrotic pathways such as JAK2/STAT3, BMP4/Smad, and PARP14/SOCS2-mediated signaling. Clinical studies and meta-analyses indicate that BoNT-A may improve scar width, pliability, vascularity, height, patient-reported symptoms, and overall aesthetic quality, particularly when used immediately after wound closure or as part of multimodal therapy. Nevertheless, evidence remains heterogeneous, with substantial variation in dose, timing, injection technique, anatomical site, outcome measures, and follow-up duration. This review summarizes current evidence on BoNT-A in scar modulation, emphasizing mechanisms, postoperative prevention, treatment of established scars, combination strategies, safety, limitations, and future directions.

References

Ali, M., Xie, B., Li, P., Chen, S., Lu, Y., Qi, F., Xiong, Z., & Li, J. (2025). Botulinum toxin A prevents hypertrophic scarring by suppressing PARP14/SOCS2-mediated M2 polarization of macrophages. Biochimica et Biophysica Acta - Molecular Cell Research, 1872(7). https://doi.org/10.1016/j.bbamcr.2025.120003

Atiyeh, B. S., & Chahine, F. (2022). Comment on the efficacy and safety of botulinum toxin injections in preventing postoperative scars and improving scar quality: A systematic review and meta-analysis—is the observed effect due to botulinum neurotoxicity? Aesthetic Plastic Surgery, 46(Suppl. 1), 182–183. https://doi.org/10.1007/s00266-021-02279-3

Bernabe, R. M., Won, P., Lin, J., Pham, C., Madrigal, P., Yenikomshian, H., & Gillenwater, T. J. (2024). Combining scar-modulating agents for the treatment of hypertrophic scars and keloids: A systematic review. Journal of Plastic, Reconstructive & Aesthetic Surgery, 88, 125–140. https://doi.org/10.1016/j.bjps.2023.10.065

Dai, X., & Lei, T. C. (2021). Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte-like cells. Basic & Clinical Pharmacology & Toxicology, 129(6), 462–469. https://doi.org/10.1111/bcpt.13661

Elradi, M., Selim, H., & Hamed, D. E. (2025). Intralesional insulin is superior to intralesional botulinum toxin-A in the treatment of keloids. Dermatologic Surgery, 51(6), 593–598. https://doi.org/10.1097/dss.0000000000004566

Fan, Y., Guo, X., Tian, Y., Li, J., & Xi, H. (2024). Botulinum toxin type A inhibits the formation of hypertrophic scar through the JAK2/STAT3 pathway. Biomolecules & Biomedicine, 25(1), 249–258. https://doi.org/10.17305/bb.2024.10906

Gao, Y., Li, W., Li, Z., Wu, F., & Wang, J. (2025). Clinical efficacy analysis of botulinum toxin type A combined with superficial radiotherapy after chest keloid surgery. Aesthetic Plastic Surgery, 49(22), 6333–6338. https://doi.org/10.1007/s00266-025-04886-w

Gill, H. S., O-Wern, L., Tiwari, P., Gill, G. K. S., Goh, C., Hung, J., Lee, J. T., Lim, T. C., Lim, J., Yap, Y. L., & Nallathamby, V. (2024). Postoperative scar management protocol for Asian patients. Aesthetic Plastic Surgery, 48(3), 461–471. https://doi.org/10.1007/s00266-023-03696-2

Ji, Q., Tang, J., Hu, H., Chen, J., & Cen, Y. (2022). Botulinum toxin type A for preventing and treating cleft lip scarring: A systematic review and meta-analysis. Journal of Cosmetic Dermatology, 21(6), 2331–2337. https://doi.org/10.1111/jocd.14941

Jiang, B., Zhang, J., Yang, W., Wang, Y., Huang, S., Qiu, J., Bian, B., Zhang, L., & Zu, W. (2024). Comparison of dual-plane micro-drop injection of botulinum toxin type A with two traditional methods for treating hypertrophic scars in the tension zone: A long-term clinical application study. Journal of Cosmetic Dermatology, 23(10), 3182–3188. https://doi.org/10.1111/jocd.16401

Khatery, B. H. M., Hussein, H. A., Abd-el-Raheem, T. A., El Hanbuli, H. M., & Yassen, N. N. (2022). Assessment of intralesional injection of botulinum toxin type A in hypertrophic scars and keloids: Clinical and pathological study. Dermatologic Therapy, 35(10). https://doi.org/10.1111/dth.15748

Lai, I.-C., Huang, G.-L., Lee, K.-C., & Wu, P.-Y. (2026). Comparative efficacy and recurrence risk of intralesional therapies for hypertrophic scars and keloids: A network meta-analysis. Aesthetic Surgery Journal, 46(2). https://doi.org/10.1093/asj/sjaf182

Li, S. H., Shan, X. J., Wang, Z. H., & Tao, S. J. (2024). Immediately injections of botulinum toxin A after surgical excision for ear keloids: A retrospective study. The Journal of Craniofacial Surgery, 35(8), 2386–2389. https://doi.org/10.1097/scs.0000000000010649

Martinez, P. F., Rogers, A. E., Mantilla-Rivas, E., Hughes, H., Melo Leal, D., Rana, M. S., Manrique, M., Rogers, G. F., & Oh, A. K. (2024). Botulinum toxin to improve scar quality in cleft lip repair: A systematic review. The Cleft Palate-Craniofacial Journal, 61(11), 1828–1835. https://doi.org/10.1177/10556656231190535

Naik, P. P. (2022). Novel targets and therapies for keloid. Clinical and Experimental Dermatology, 47(3), 507–515. https://doi.org/10.1111/ced.14920

Santillan, M. R., Ozog, D., & Wu, W. (2024). Using neuromodulators to improve scar formation, keloids, rosacea, and antiaging. Dermatologic Surgery, 50(9S), S91–S96. https://doi.org/10.1097/dss.0000000000004353

Shi, H., Zhang, P., Zhang, J., Sun, J., & Lv, T. (2025). Dose-dependent effects of botulinum toxin type A on prevention of postoperative scars in various regions in the body: A prospective, double-blind randomized controlled trial. Aesthetic Plastic Surgery, 49(3), 862–874. https://doi.org/10.1007/s00266-024-04351-0

Yang, H. A., Jheng, W. L., Yu, J., Huang, J. Y., Cheng, K. Y., & Lee, J. J. (2024). Comparative efficacy of drug interventions for keloids: A network meta-analysis. Annals of Plastic Surgery, 92(1S Suppl. 1), S52–S59. https://doi.org/10.1097/sap.0000000000003759

Yue, S., & Ju, M. (2022). Letter to the editor: Evaluation of efficacy of corticosteroid and corticosteroid combined with botulinum toxin type A in the treatment of keloid and hypertrophic scars: A meta-analysis. Aesthetic Plastic Surgery, 46(4), 2095–2096. https://doi.org/10.1007/s00266-021-02539-2

Zhang, S., Li, K., Yu, Z., Chai, J., Zhang, Z., Zhang, Y., & Min, P. (2022). Dramatic effect of botulinum toxin type A on hypertrophic scar: A promising therapeutic drug and its mechanism through the SP-NK1R pathway in cutaneous neurogenic inflammation. Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.820817

Zhang, S., Peng, Y., Fan, H., Zhang, Y., & Min, P. (2022). Microneedle delivery of botulinum toxin type A combined with hyaluronic acid for the synergetic management of multiple sternal keloids with oily skin: A retrospective clinical investigation. Journal of Cosmetic Dermatology, 21(11), 5601–5609. https://doi.org/10.1111/jocd.15216