Current research status and progress of laser therapy in wound healing

Abstract

A wound is a disruption in the integrity of the skin or other body tissues. The application of laser therapy can facilitate microscopic debridement by utilizing photothermal action to remove necrotic tissue and employing photobiological regulation to expedite epithelial growth while reducing the duration of acute inflammation. Laser therapy can regulate Heat Shock Proteins, Matrix Metalloproteinases, and inflammatory factors in wound tissues. This promotes wound re-epithelialization and organizes collagen fibers, helping to reduce scar formation. Additionally, laser therapy utilizes photochemical action for sterilization and photomechanical action to disrupt bacterial biofilms, thereby facilitating drug delivery and absorption. Numerous studies have substantiated the efficacy of laser therapy in promoting chronic wound re-epithelialization, diminishing scarring in acute wounds, and enhancing both the speed and quality of overall wound healing. However, further large-scale studies are required to explore the optimal parameter range for laser wound therapy. Consequently, laser therapy represents a promising option for managing various types of wounds, offering prospects for further reduction in scar formation.

Keywords

Wound healing / laser therapy / acute wound / chronic wound / re-epithelization / scarless

References

[1] Kyaw BM,Järbrink K,Martinengo L,Car J,Harding K,Schmidtchen A. Need for improved definition of “chronic wounds” in clinical studies Acta Derm Venereol 2018 98 157 8

[2] Jones RE,Foster DS,Longaker MT. Management of chronic wounds - 2018 JAMA 2018 320 1481 2

[3] Rezaie F,Momeni-Moghaddam M,Naderi-Meshkin H. Regeneration and repair of skin wounds: various strategies for treatment Int J Low Extrem Wounds 2019 18 247 61

[4] Martinengo L,Olsson M,Bajpai R.et al. Prevalence of chronic wounds in the general population: systematic review and meta-analysis of observational studies Ann Epidemiol 2019 29 8 15

[5] Olsson M,Järbrink K,Divakar U.et al. The humanistic and economic burden of chronic wounds: a systematic review Wound Repair Regen 2019 27 114 25

[6] Graves N,Phillips CJ,Harding K. A narrative review of the epidemiology and economics of chronic wounds Br J Dermatol 2022 187 141 8

[7] Maxant G,Pastrav M,Gogeneata I,Bajcz C,Bertaux AC. Clinical and medico-economic benefits of remote monitoring of chronic wounds Int Wound J 2025 22 e70140 PMC11868980

[8] Nussbaum SR,Carter MJ,Fife CE.et al. An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds Value Health 2018 21 27 32

[9] Hsieh JC,Maisel-Campbell AL,Joshi CJ,Zielinski E,Galiano RD. Daily quality-of-life impact of scars: an interview-based foundational study of patient-reported themes Plast Reconstr Surg Glob Open 2021 9 e3522 PMC8049395

[10] Pirakitikulr N,Martin JJ,Wester ST. Laser resurfacing for the management of periorbital scarring Plast Aesthet Res 2020 7 67 PMC7771834

[11] Mayer DO. The pivotal role of debridement in wound healing J Wound Care 2024 33 366

[12] Wynn M. The benefits and harms of cleansing for acute traumatic wounds: a narrative review Adv Skin Wound Care 2021 34 488 92

[13] Warriner RA 3rd, Wilcox JR, Carter MJ, Stewart DG. More frequent visits to wound care clinics result in faster times to close diabetic foot and venous leg ulcers Adv Skin Wound Care 2012 25 494 501

[14] De Decker I,De Graeve L,Hoeksema H.et al. Enzymatic debridement: past, present, and future Acta Chir Belg 2022 122 279 95

[15] Liu E,Hu X,Zhang W.et al. Efficacy and safety of ultrasound-assisted wound debridement in the treatment of diabetic foot ulcers: a systematic review and meta-analysis of 11 randomized controlled trials Front Endocrinol 2024 15 1393251 PMC11094243

[16] Kataoka Y,Kunimitsu M,Nakagami G,Koudounas S,Weller CD,Sanada H. Effectiveness of ultrasonic debridement on reduction of bacteria and biofilm in patients with chronic wounds: a scoping review Int Wound J 2021 18 176 86 PMC8244003

[17] Bowers S,Franco E. Chronic wounds: evaluation and management Am Fam Physician 2020 101 159 66

[18] Legemate CM,Kwa KAA,Goei H.et al. HyCon Study Group Hydrosurgical and conventional debridement of burns: randomized clinical trial Br J Surg 2022 109 332 9 PMC10364696

[19] Hajhosseini B,Chiou GJ,Dori G.et al. Er:YAG laser vs. sharp debridement in management of chronic wounds: effects on pain and bacterial load Wound Repair Regen 2020 28 118 25

[20] Sherrill JD,Finlay D,Binder RL.et al. Transcriptomic analysis of human skin wound healing and rejuvenation following ablative fractional laser treatment PLoS One 2021 16 e0260095 PMC8629261

[21] Karmisholt KE,Banzhaf CA,Glud M.et al. Laser treatments in early wound healing improve scar appearance: a randomized split-wound trial with nonablative fractional laser exposures vs. untreated controls Br J Dermatol 2018 179 1307 14

[22] Parikh UM,Mentz J,Collier I.et al. Strategies to minimize surgical scarring: translation of lessons learned from bedside to bench and back Adv Wound Care 2022 11 311 29

[23] Nube VL,Alison JA,Twigg SM. Diabetic foot ulcers: weekly versus second-weekly conservative sharp wound debridement J Wound Care 2023 32 383 90

[24] Ditmars FS,Kay KE,Broderick TC,Fagg WS. Use of amniotic membrane in hard-to-heal wounds: a multicentre retrospective study J Wound Care 2024 33 S44 50

[25] Mathioudaki E,Vitsos A,Rallis MC. Proteolytic enzymes and wound debridement: a literature review Wounds 2024 36 357 65

[26] Afzal H,Dawson E,Fonseca R.et al. Negative pressure wound therapy with and without instillation in necrotizing soft tissue infections Surg Infect 2024 25 199 205

[27] Matthews MR,Fernández LG,Hermans MH,Chakravarthy D. The efficient application of instilling negative pressure wound therapy with a hypochlorous acid-preserved wound cleanser: a case series and practical advice Wounds 2024 36 148 53

[28] Gold MH,McGuire M,Mustoe TA.et al. International Advisory Panel on Scar Management Updated international clinical recommendations on scar management: part 2 - algorithms for scar prevention and treatment Dermatol Surg 2014 40 825 31

[29] Yang X,Lohsiriwat V,Chang FCS.et al. Real-world management of abnormal scarring using topical silicone gel: expert consensus and case series from the Asian SCARS Expert Group Drugs Context 2023 12 PMC10321470

[30] Seago M,Shumaker PR,Spring LK.et al. Laser treatment of traumatic scars and contractures: 2020 International Consensus Recommendations Lasers Surg Med 2020 52 96 116

[31] Ma Y,Barnes SP,Chen YY,Moiemen NS,Lord JM,Sardeli AV. Influence of scar age, laser type and laser treatment intervals on adult burn scars: a systematic review and meta-analysis PLoS One 2023 18 e0292097 PMC10529539

[32] Anderson RR,Donelan MB,Hivnor C.et al. Laser treatment of traumatic scars with an emphasis on ablative fractional laser resurfacing: consensus report JAMA Dermatol 2014 150 187 93

[33] Du F,Yu Y,Zhou Z,Wang L,Zheng S. Early treatment using fractional CO₂ laser before skin suture during scar revision surgery in Asians J Cosmet Laser Ther 2018 20 102 5

[34] Nunez JH,Strong AL,Comish P.et al. A review of laser therapies for the treatment of scarring and vascular anomalies Adv Wound Care 2023 12 68 84

[35] Zhang Y. Chinese Association of Plastics and Aesthetics Scar Medicine Branch National expert consensus on early management of scars (2020 version) Zhonghua Shao Shang Za Zhi 2021 37 113 25 (in Chinese)

[36] Lv K,Xia Z. Chinese Consensus Panel on the Prevention and Treatment of Scars Chinese expert consensus on clinical prevention and treatment of scar Burns Trauma 2018 6 27 PMC6154406

[37] Shen S,Cai Y,Song X,Xiang W. The efficacy of fractional carbon dioxide laser in surgical scars treatment: a system review and meta-analysis Aesthetic Plast Surg 2023 47 340 50

[38] Friedman O,Gofstein D,Arad E,Gur E,Sprecher E,Artzi O. Laser pretreatment for the attenuation of planned surgical scars: a randomized self-controlled hemi-scar pilot study J Plast Reconstr Aesthet Surg 2020 73 893 8

[39] Aoki A,Mizutani K,Taniguchi Y.et al. Current status of Er:YAG laser in periodontal surgery Jpn Dent Sci Rev 2024 60 1 14 PMC10750110

[40] Haykal D,Cartier H,Goldberg D,Gold M. Advancements in laser technologies for skin rejuvenation: a comprehensive review of efficacy and safety J Cosmet Dermatol 2024 23 3078 89

[41] Maghfour J,Ozog DM,Mineroff J,Jagdeo J,Kohli I,Lim HW. Photobiomodulation CME part I: overview and mechanism of action J Am Acad Dermatol 2024 91 793 802

[42] Duplechain JK. Ablative laser therapy of skin Facial Plast Surg Clin North Am 2023 31 463 73

[43] Thomsen S. Pathologic analysis of photothermal and photomechanical effects of laser-tissue interactions Photochem Photobiol 1991 53 825 35

[44] Walsh JT Jr, Flotte TJ, Deutsch TF. Er:YAG laser ablation of tissue: effect of pulse duration and tissue type on thermal damage Lasers Surg Med 1989 9 314 26

[45] Karkada G,Maiya GA,Arany P,Kg MR,Adiga S,Kamath SU. Dose-response relationship of photobiomodulation therapy and oxidative stress markers in healing dynamics of diabetic neuropathic ulcers in Wistar rats J Diabetes Metab Disord 2023 22 393 400 PMC10225440

[46] Anderson RR,Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation Science 1983 220 524 7

[47] DiPietro LA. Angiogenesis and wound repair: when enough is enough J Leukoc Biol 2016 100 979 84 PMC6608066

[48] Yu W,Zhu J,Yu W,Lyu D,Lin X,Zhang Z. A split-face, single-blinded, randomized controlled comparison of alexandrite 755-nm picosecond laser versus alexandrite 755-nm nanosecond laser in the treatment of acquired bilateral nevus of Ota-like macules J Am Acad Dermatol 2018 79 479 86

[49] Ma SY,Gong YQ,Zhang WJ.et al. Split-face comparison of the efficacy of picosecond 532 nm Nd:YAG laser and Q-switched 755 nm Alexandrite laser for treatment of freckles J Cosmet Laser Ther 2022 24 22 7

[50] Leyane TS,Jere SW,Houreld NN. Cellular signalling and photobiomodulation in chronic wound repair Int J Mol Sci 2021 22 PMC8537491

[51] Mester E,Spiry T,Szende B. Effect of laser rays on wound healing Bull Soc Int Chir 1973 32 169 73

[52] Mester E,Ludány G,Sellyei M,Szende B,Gyenes G,Tota GJ. Studies on the inhibiting and activating effects of laser beams Langenbecks Arch Chir 1968 322 1022 7 (in German)

[53] Ryu HS,Lim NK,Padalhin AR.et al. Improved healing and macrophage polarization in oral ulcers treated with photobiomodulation (PBM) Lasers Surg Med 2022 54 600 10

[54] Zhang G,Yi L,Wang C.et al. Photobiomodulation promotes angiogenesis in wound healing through stimulating the nuclear translocation of VEGFR2 and STAT3 J Photochem Photobiol B 2022 237 112573

[55] Mathioudaki E,Rallis M,Politopoulos K,Alexandratou E. Photobiomodulation and wound healing: low-level laser therapy at 661 nm in a scratch assay keratinocyte model Ann Biomed Eng 2024 52 376 85 PMC10808316

[56] Barolet AC,Villarreal AM,Jfri A,Litvinov IV,Barolet D. Low-intensity visible and near-infrared light-induced cell signaling pathways in the skin: a comprehensive review Photobiomodul Photomed Laser Surg 2023 41 147 66

[57] Kasowanjete P,Houreld NN,Abrahamse H. The effect of photomodulation on fibroblast growth factor and the Ras/MAPK signalling pathway: a review J Wound Care 2022 31 832 45

[58] Karu T. Mitochondrial mechanisms of photobiomodulation in context of new data about multiple roles of ATP Photomed Laser Surg 2010 28 159 60

[59] Chung H,Dai T,Sharma SK,Huang YY,Carroll JD,Hamblin MR. The nuts and bolts of low-level laser (light) therapy Ann Biomed Eng 2012 40 516 33 PMC3288797

[60] Dompe C,Moncrieff L,Matys J.et al. Photobiomodulation-underlying mechanism and clinical applications J Clin Med 2020 9 PMC7356229

[61] Glass GE. Photobiomodulation: a review of the molecular evidence for low level light therapy J Plast Reconstr Aesthet Surg 2021 74 1050 60

[62] da Silva TG,Ribeiro RS,Mencalha AL,de Souza Fonseca A. Photobiomodulation at molecular, cellular, and systemic levels Lasers Med Sci 2023 38 136

[63] Mineroff J,Maghfour J,Ozog DM,Lim HW,Kohli I,Jagdeo J. Photobiomodulation CME part II: clinical applications in dermatology J Am Acad Dermatol 2024 91 805 15

[64] Agostinis P,Berg K,Cengel KA.et al. Photodynamic therapy of cancer: an update CA Cancer J Clin 2011 61 250 81 PMC3209659

[65] Warrier A,Mazumder N,Prabhu S,Satyamoorthy K,Murali TS. Photodynamic therapy to control microbial biofilms Photodiagnosis Photodyn Ther 2021 33 102090

[66] Hou C,Zhang L,Wang L.et al. A meta-analysis and systematic review of photodynamic therapy for diabetic foot ulcers Photodiagnosis Photodyn Ther 2024 48 104228

[67] Zhang D,Leong ASW,McMullin G. Blue light therapy in the management of chronic wounds: a narrative review of its physiological basis and clinical evidence Wounds 2023 35 91 8

[68] Tripodi N,Sidiroglou F,Apostolopoulos V,Feehan J. Transcriptome analysis of the effects of polarized photobiomodulation on human dermal fibroblasts J Photochem Photobiol B 2023 242 112696

[69] Francis NC,Yao W,Grundfest WS,Taylor ZD. Laser-generated shockwaves as a treatment to reduce bacterial load and disrupt biofilm IEEE Trans Biomed Eng 2017 64 882 9 PMC6066283

[70] Yao W,Kuan EC,Francis NC,St John MA,Grundfest WS,Taylor ZD. Laser-generated shockwaves enhance antibacterial activity against biofilms in vitro Lasers Surg Med 2017 49 539 47 PMC7453678

[71] Orringer JS,Sachs DL,Shao Y.et al. Direct quantitative comparison of molecular responses in photodamaged human skin to fractionated and fully ablative carbon dioxide laser resurfacing Dermatol Surg 2012 38 1668 77

[72] Maddaluno L,Urwyler C,Werner S. Fibroblast growth factors: key players in regeneration and tissue repair Development 2017 144 4047 60

[73] Werner S,Peters KG,Longaker MT,Fuller-Pace F,Banda MJ,Williams LT. Large induction of keratinocyte growth factor expression in the dermis during wound healing Proc Natl Acad Sci U S A 1992 89 6896 900 PMC49611

[74] Prignano F,Campolmi P,Bonan P.et al. Fractional CO₂ laser: a novel therapeutic device upon photobiomodulation of tissue remodeling and cytokine pathway of tissue repair Dermatol Ther 2009 22 Suppl 1 S8 15

[75] Bai J,Li L,Kou N.et al. Low level laser therapy promotes bone regeneration by coupling angiogenesis and osteogenesis Stem Cell Res Ther 2021 12 432 PMC8330075

[76] Mirsky N,Krispel Y,Shoshany Y,Maltz L,Oron U. Promotion of angiogenesis by low energy laser irradiation Antioxid Redox Signal 2002 4 785 90

[77] Jiang B,Tang R,Zheng D.et al. Evaluation of the efficacy of ultrapulsed CO₂ laser in chronic wounds Lasers Surg Med 2021 53 443 9

[78] El Nawam H,El Backly R,Zaky A,Abdallah A. Low-level laser therapy affects dentinogenesis and angiogenesis of in vitro 3D cultures of dentin-pulp complex Lasers Med Sci 2019 34 1689 98

[79] Keshri GK,Yadav A,Verma S,Kumar B,Gupta A. Effects of pulsed 810 nm Al-Ga-As diode laser on wound healing under immunosuppression: a molecular insight Lasers Surg Med 2020 52 424 36

[80] Kang D. Enhancing Skin flap survival with preoperative carbon dioxide fractional laser treatment: a novel approach in reconstructive surgery J Craniofac Surg 2025 36 334 8

[81] Cambier S,Gouwy M,Proost P. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention Cell Mol Immunol 2023 20 217 51 PMC9890491

[82] Restivo TE,Mace KA,Harken AH,Young DM. Application of the chemokine CXCL12 expression plasmid restores wound healing to near normal in a diabetic mouse model J Trauma 2010 69 392 8

[83] Schmitt L,Huth S,Amann PM.et al. Direct biological effects of fractional ultrapulsed CO₂ laser irradiation on keratinocytes and fibroblasts in human organotypic full-thickness 3D skin models Lasers Med Sci 2018 33 765 72

[84] Helbig D,Bodendorf MO,Grunewald S,Kendler M,Simon JC,Paasch U. Immunohistochemical investigation of wound healing in response to fractional photothermolysis J Biomed Opt 2009 14 064044

[85] Peña OA,Martin P. Cellular and molecular mechanisms of skin wound healing Nat Rev Mol Cell Biol 2024 25 599 616

[86] Rousselle P,Braye F,Dayan G. Re-epithelialization of adult skin wounds: cellular mechanisms and therapeutic strategies Adv Drug Deliv Rev 2019 146 344 65

[87] Dillmann WH. Heat shock proteins and protection against ischemic injury Infect Dis Obstet Gynecol 1999 7 55 7 PMC1784710

[88] Williams RS. Heat shock protein 47: a chaperone for the fibrous cap? Circulation 2000;101:1227-8

[89] Köhler A,Mörgelin M,Gebauer JM.et al. New specific HSP47 functions in collagen subfamily chaperoning FASEB J 2020 34 12040 52

[90] Genest O,Wickner S,Doyle SM. Hsp90 and Hsp70 chaperones: collaborators in protein remodeling J Biol Chem 2019 294 2109 20 PMC6369297

[91] Makboul M,Makboul R,Abdelhafez AH,Hassan SS,Youssif SM. Evaluation of the effect of fractional CO₂ laser on histopathological picture and TGF-β1 expression in hypertrophic scar J Cosmet Dermatol 2014 13 169 79

[92] Paasch U,Sonja G,Haedersdal M. Synergistic skin heat shock protein expression in response to combined laser treatment with a diode laser and ablative fractional lasers Int J Hyperthermia 2014 30 245 9

[93] Salo T,Mäkelä M,Kylmäniemi M,Autio-Harmainen H,Larjava H. Expression of matrix metalloproteinase-2 and -9 during early human wound healing. Lab Investig J Tech Methods Pathol 1994;70:176-82

[94] Kümper M,Zamek J,Steinkamp J,Pach E,Mauch C,Zigrino P. Role of MMP3 and fibroblast-MMP14 in skin homeostasis and repair Eur J Cell Biol 2022 101 151276

[95] Kostov K,Blazhev A. Changes in serum levels of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 in Patients with essential hypertension Bioengineering 2022 9 119 PMC8945798

[96] Shumaker PR,Kwan JM,Badiavas EV,Waibel J,Davis S,Uebelhoer NS. Rapid healing of scar-associated chronic wounds after ablative fractional resurfacing Arch Dermatol 2012 148 1289 93

[97] Madni TD,Lu KB,Imran JB.et al. Chronic burn wound treatment by Erbium: YAG fractional ablation: first described report and literature review Burns 2019 45 256 8

[98] Lee HN,Bae JM,Goo BCL,Park YM. Promotion of wound healing through low-fluence ablative fractional laser treatment in diabetic mice Lasers Med Sci 2019 34 421 5

[99] Guan H,Zhang D,Ma X.et al. Efficacy and safety of CO₂ laser in the treatment of chronic wounds: a retrospective matched cohort trial Lasers Surg Med 2022 54 490 501

[100] Rohrer TE,Ugent SJ. Evaluating the efficacy of using a short-pulsed erbium:YAG laser for intraoperative resurfacing of surgical wounds Lasers Surg Med 2002 30 101 5

[101] Phillips TJ,Morton LM,Uebelhoer NS,Dover JS. Ablative fractional carbon dioxide laser in the treatment of chronic, posttraumatic, lower-extremity ulcers in elderly patients JAMA Dermatol 2015 151 868 71

[102] Zhang Y,Liu Y,Cai B.et al. Improvement of surgical scars by early intervention with carbon dioxide fractional laser Lasers Surg Med 2020 52 137 48

[103] Weinstein Velez M,Prezzano J,Bell M,Widgerow A. A single center, prospective, randomized, blinded study to evaluate the efficacy and safety of a topical tripeptide/hexapeptide anhydrous gel when used pre- and post- hybrid fractional laser for the treatment of acne scars Clin Cosmet Investig Dermatol 2022 15 2763 74 PMC9766513

[104] Kuppa SS,Kang JY,Kim JY.et al. Red-light LED therapy promotes wound regeneration by upregulating COL1A1, COL2A1, VEGF and reducing IL-1β for anti-inflammation Lasers Med Sci 2025 40 171

[105] Riedemann HI,Marquardt Y,Jansen M,Baron JM,Huth S. Biological effect of laser-assisted scar healing (LASH) on standardized human three-dimensional wound healing skin models using fractional non-ablative 1540 nm Er:Glass or 1550 nm diode lasers Lasers Surg Med 2024 56 100 6

[106] Pulumati A,Jaalouk D,Algarin YA,Nouri K. The role of 755-nm alexandrite picosecond laser in melasma management Arch Dermatol Res 2023 316 60

[107] Bao MZ,Zhou LB,Zhao L.et al. Efficacy of lidocaine wet compress combined with red-light irradiation for chronic wounds World J Clin Cases 2023 11 7277 83 PMC10643062

[108] Prudente D,Hauser F,Mettraux G,Di Bella E,Krejci I. Efficacy of one-time application of low-level laser therapy in the management of complications after third molar surgery: a retrospective practice-based study Am J Dent 2023 36 21 4

[109] Clayton JL,Edkins R,Cairns BA,Hultman CS. Incidence and management of adverse events after the use of laser therapies for the treatment of hypertrophic burn scars Ann Plast Surg 2013 70 500 5