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595-nm pulsed dye laser combined with fractional CO2 laser reduces hypertrophic scar through down-regulating TGFβ1 and PCNA

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Abstract

595-nm pulsed dye laser and fractional CO2 laser have been demonstrated effective to treat hypertrophic scar. The underlying mechanism may involve transforming growth factor-beta1 (TGFβ1) and proliferating cell nuclear antigen (PCNA), but remains to be clarified. Our study was performed to investigate how 595-nm pulsed dye laser combined with fractional CO2 laser treats hypertrophic scars in a rabbit model through regulating the expression of TGFβ1 and PCNA. Twenty-four New Zealand white rabbits were randomly divided into control group, pulsed dye laser group, fractional CO2 laser group, and pulsed dye laser + fractional CO2 laser (combination) group. Surgical wounds were made and allowed to grow into hypertrophic scars at day 28. Next, 595-nm pulsed dye laser (fluence: 15 J/cm2; square: 7 mm; pulse duration: 10 ms) was used in pulsed dye laser and combination group, while fractional CO2 laser (combo mode, deep energy: 12.5 mJ; super energy: 90 mJ) in fractional CO2 laser and combination groups, once every 4 weeks for 3 times. The appearance and thickness of hypertrophic scar samples were measured with hematoxylin-eosin and Van Gieson’s straining. The expressions of TGFβ1 and PCNA were evaluated by immunohistochemical and western blot analysis. A significant improvement was noted in the thickness, size, hardness, and histopathology of hypertrophic scar samples after laser treatment, especially in combination group. Scar Elevation Index (SEI), fiber density (NA), and collagen fiber content (AA) decreased most significantly in combination group (2.10 ± 0.14; 2506 ± 383.00; 22.98 ± 2.80%) compared to 595-nm pulsed dye laser group (3.35 ± 0.28; 4857 ± 209.40; 42.83 ± 1.71%) and fractional CO2 laser group (2.60 ± 0.25; 3995 ± 224.20; 38.33 ± 3.01%) (P < 0.001). Furthermore, TGFβ1 and PCNA expressions were more suppressed in combination group (8.78 ± 1.03; 7.81 ± 1.51) than in 595-nm pulsed dye laser (14.91 ± 1.68; 15.73 ± 2.53) and fractional CO2 laser alone group (15.96 ± 1.56; 16.13 ± 1.72) (P < 0.001). The combination of 595-nm pulsed dye laser with fractional CO2 laser can improve the morphology and histology of hypertrophic scars in a rabbit model through inhibiting the expression of TGFβ1 and PCNA protein. Our findings can pave the way for new clinical treatment strategies for hypertrophic scars.

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References

  1. Zhang J, Li Y, Bai X et al (2018) Recent advances in hypertrophic scar. Histol Histopathol 33:27–39

    CAS  PubMed  Google Scholar 

  2. Finnerty CC, Jeschke MG, Branski LK et al (2016) Hypertrophic scarring: the greatest unmet challenge after burn injury. Lancet 388(10052):1427–1436

    Article  Google Scholar 

  3. Artzi O, Friedman O, Al-Niaimi F et al (2020) Mitigation of postsurgical scars using lasers: a review. Plast Reconstr Surg Glob Open 8(4):e2746 Published 2020 Apr 24

    Article  Google Scholar 

  4. Berman B, Maderal A, Raphael B (2017) Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg 43(Suppl 1):S3–S18

    Article  CAS  Google Scholar 

  5. Zhu Z, Ding J, Tredget EE (2016) The molecular basis of hypertrophic scars. Burns Trauma 4:2 Published 2016 Jan 21

    Article  Google Scholar 

  6. Toro DD, Dedhia R, Tollefson TT (2016) Advances in scar management: prevention and management of hypertrophic scars and keloids. Curr Opin Otolaryngol Head Neck Surg 24(4):324–332

    Google Scholar 

  7. Kuehlmann B, Stern-Buchbinder Z, Wan DC et al (2019) Beneath the surface: a review of laser remodeling of hypertrophic scars and burns. Adv Wound Care (New Rochelle) 8(4):168–176

    Article  Google Scholar 

  8. Seago M, Shumaker PR, Spring LK et al (2020) Laser treatment of traumatic scars and contractures: 2020 international consensus recommendations. Lasers Surg Med 52(2):96–116

    Article  Google Scholar 

  9. Pongcharoen P, Pongcharoen B, Disphanurat W (2019) The effectiveness of a 595 nm pulsed-dye-laser in the treatment of surgical scars following a knee arthroplasty. J Cosmet Laser Ther 21(6):352–356

    Article  Google Scholar 

  10. Lin L, Guo P, Wang X et al (2019) Effective treatment for hypertrophic scar with dual-wave-length PDL and Nd:YAG in Chinese patients. J Cosmet Laser Ther 21(4):228–233

    Article  Google Scholar 

  11. Safra T, Shehadeh W, Koren A et al (2019) Early intervention with pulse dye and CO2 ablative fractional lasers to improve cutaneous scarring post-lumpectomy: a randomized controlled trial on the impact of intervention on final cosmesis. Lasers Med Sci 34(9):1881–1887

    Article  Google Scholar 

  12. Forbat E, Al-Niaimi F (2019) Nonvascular uses of pulsed dye laser in clinical dermatology [published online ahead of print, 2019 Apr 19]. J Cosmet Dermatol. https://doi.org/10.1111/jocd.12924

  13. Radmanesh M, Mehramiri S, Radmanesh R (2019) Fractional CO2 laser is as effective as pulsed dye laser for the treatment of hypertrophic scars. J Dermatolog Treat:1–4. https://doi.org/10.1080/09546634.2019.1687821

  14. Patel SP, Nguyen HV, Mannschreck D et al (2019) Fractional CO2 laser treatment outcomes for pediatric hypertrophic burn scars. J Burn Care Res 40(4):386–391

    Article  Google Scholar 

  15. Anderson RR, Parrish JA (1981) Microvasculature can be selectively damaged using dye lasers: a basic theory and experimental evidence in human skin. Lasers Surg Med 1(3):263–276

    Article  CAS  Google Scholar 

  16. Liu A, Moy RL, Ross EV et al (2012) Pulsed dye laser and pulsed dye laser-mediated photodynamic therapy in the treatment of dermatologic disorders. Dermatol Surg 38(3):351–366

    Article  CAS  Google Scholar 

  17. Liu XJ, Ouyang HW, Lei Y et al (2020) Moist exposed burn therapy in recovery of patients with immature, red hypertrophic scars successfully treated with a pulsed dye laser in combination with a fractional CO2 laser. J Cosmet Dermatol 19(6):1353–1358

    Article  Google Scholar 

  18. Nouri K, Rivas MP, Stevens M et al (2009) Comparison of the effectiveness of the pulsed dye laser 585 nm versus 595 nm in the treatment of new surgical scars. Lasers Med Sci 24(5):801–810

    Article  Google Scholar 

  19. Lei Y, Ouyang HW, Tan J (2020) Effect of pulsed dye laser in combination with ultra-pulsed fractional carbon dioxide laser in treating pediatric burn scars at early stage. Zhonghua Shao Shang Za Zhi 36(5):357–362.595

    CAS  PubMed  Google Scholar 

  20. Lee SJ, Suh DH, Lee JM et al (2016) Dermal remodeling of burn scar by fractional CO2 laser. Aesthet Plast Surg 40:761–768

    Article  Google Scholar 

  21. Makboul M, Makboul R, Abdelhafez AH, Hassan SS, Youssif SM (2014) Evaluation of the effect of fractional CO2 laser on histopathological picture and TGF-β1 expression in hypertrophic scar. J Cosmet Dermatol 13(3):169–179

    Article  Google Scholar 

  22. Mignon C, Rodriguez AH, Palero JA et al (2016) Fractional laser photothermolysis using Bessel beams. Biomed Opt Express 7(12):4974–4981

    Article  CAS  Google Scholar 

  23. Azzam OA, Bassiouny DA, El-Hawary MS et al (2016) Treatment of hypertrophic scars and keloids by fractional carbon dioxide laser: a clinical, histological, and immunohistochemical study. Lasers Med Sci 31(1):9–18

    Article  CAS  Google Scholar 

  24. Poetschke J, Dornseifer U, Clementoni MT et al (2017) Ultrapulsed fractional ablative carbon dioxide laser treatment of hypertrophic burn scars: evaluation of an in-patient controlled, standardized treatment approach. Lasers Med Sci 32(5):1031–1040

    Article  Google Scholar 

  25. Levi B, Ibrahim A, Mathews K et al (2016) The use of CO2 fractional photothermolysis for the treatment of burn scars. J Burn Care Res 37(2):106–114

    Article  Google Scholar 

  26. Rodriguez-Menocal L, Davis SS, Becerra S et al (2018) Assessment of ablative fractional CO2 laser and Er:YAG laser to treat hypertrophic scars in a red Duroc pig model. J Burn Care Res 39(6):954–962

    Article  Google Scholar 

  27. Limandjaja GC, van den Broek LJ, Breetveld M et al (2018) Characterization of in vitro reconstructed human normotrophic, hypertrophic, and keloid scar models. Tissue Eng Part C Methods 24(4):242–253

    Article  CAS  Google Scholar 

  28. Lian N, Li T (2016) Growth factor pathways in hypertrophic scars: molecular pathogenesis and therapeutic implications. Biomed Pharmacother 84:42–50

    Article  CAS  Google Scholar 

  29. Guo J, Lin Q, Shao Y et al (2017) miR-29b promotes skin wound healing and reduces excessive scar formation by inhibition of the TGF-beta1/Smad/CTGF signaling pathway. Can J Physiol Pharmacol 95(4):437–442

    Article  CAS  Google Scholar 

  30. Su S, Xin S, Yu Y (2000) The study of expression and distribution of PCNA in hypertrophic scar tissue. Zhonghua Zheng Xing Wai Ke Za Zhi 16(2):73–74

    CAS  PubMed  Google Scholar 

  31. Zhang Y, Hong WL, Li ZM et al (2020) The mechanism of miR-222 targets matrix metalloproteinase 1 in regulating fibroblast proliferation in hypertrophic scars. Aesthet Plast Surg. https://doi.org/10.1007/s00266-020-01727-w

  32. Zhao JC, Zhang BR, Hong L et al (2018) Extracorporeal shock wave therapy with low-energy flux density v v inhibits hypertrophic scar formation in an animal model. Int J Mol Med 41(4):1931–1938

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Hosoya A, Lee JM, Cho SW et al (2008) Morphological evidence of basal keratinocyte migration during the re-epithelialization process. Histochem Cell Biol 130(6):1165–1175

    Article  CAS  Google Scholar 

  34. Chen Lixin, Wang Ying, Lin Yangyang, et al. Effect of pulsed dye laser on the expression of TGF - β 1 and TGF - β 3 in scar fibroblasts in vitro. Chin J Integr Trad West Med Dermatovenereol, 2019, 18(01): 11–14.595

  35. Zhang Xingcun, Li Datie, An Lisa, et al. Effects of IPL and 595 nm PDL on PCNA and TGF- β in hypertrophic scar of rabbit ears. Chin J Dermatol Venereol, 2014,28 (02): 123–127

  36. Zuccaro J, Muser I, Singh M et al (2018) Laser therapy for pediatric burn scars: focusing on a combined treatment approach. J Burn Care Res 39(3):457–462

    Article  Google Scholar 

  37. Ouyang HW, Li GF, Lei Y et al (2018) Comparison of the effectiveness of pulsed dye laser vs pulsed dye laser combined with ultrapulse fractional CO2 laser in the treatment of immature red hypertrophic scars. J Cosmet Dermatol 17(1):54–60

    Article  Google Scholar 

  38. Li N, Yang L, Cheng J et al (2018) Clinical comparative study of pulsed dye laser and ultra-pulsed fractional carbon dioxide laser in the treatment of hypertrophic scars after burns. Zhonghua Shao Shang Za Zhi 34(9):603–607.595

    CAS  PubMed  Google Scholar 

  39. Barnouti ZP, Owtad P, Shen G et al (2011) The biological mechanisms of PCNA and BMP in TMJ adaptive remodeling. Angle Orthod 81(1):91–99

    Article  Google Scholar 

  40. Gong YF, Zhang XM, Liu F et al (2016) Inhibitory effect of recombinant human endostatin on the proliferation of hypertrophic scar fibroblasts in a rabbit ear model. Eur J Pharmacol 791:647–654 PCNA

    Article  CAS  Google Scholar 

  41. Xu JH, Zhao WY, Fang QQ et al (2020) Co-transfection of hepatocyte growth factor and truncated TGF-β type II receptor inhibit scar formation. Braz J Med Biol Res 53(1):e9144 Published 2020 Jan 13

    Article  CAS  Google Scholar 

Download references

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The idea of our study is supported by (omitting author information due to magazine requirements). (Omitting author information due to magazine requirements) help us to collect and analyze photo and dates. And associate (omitting author information due to magazine requirements) provided the kind advice.

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Zhang, J., Zhou, S., Xia, Z. et al. 595-nm pulsed dye laser combined with fractional CO2 laser reduces hypertrophic scar through down-regulating TGFβ1 and PCNA. Lasers Med Sci 36, 1625–1632 (2021). https://doi.org/10.1007/s10103-020-03240-7

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