Clinical Study: Use of a Proprietary Near-Infrared Laser For Wound Healing

The influence of a new near-infrared laser device on the gene expression profile of human skin relative to an equivalent, near-infrared LED device was evaluated.

12 Minute read
written by Graeme E. Glass, MBChB, PhD, FRCS(Plast); András Mérai, MD; Szabolcs Molnár, MD, PhD, Research Scientists
2025-01-13 (Updated 2026-07-22)

medically reviewed by Dr Graeme E. Glass, MD PhD, Plastic Surgeon, Associate Professor of Surgery, LYMA Aesthetic Director

Abstract Background

Nonthermal light energy has been used to enhance wound healing. This is known as photobiomodulation. Although preclinical evidence is largely based on laser light, light-emitting diodes (LEDs) form the mainstay of clinical studies owing to the lack of available lasers for nonclinical use. However, it is speculated the 2 technologies exhibit dissimilar biological responses.

Objectives

The influence of a new, commercially available near-infrared laser device on the gene expression profile of human skin relative to an equivalent, near-infrared LED device was evaluated. Additionally, the wound healing potential of the device was examined in practice.

Methods

Defatted human skin was exposed to the laser (3), LED (3), or negative control (3) for 5 days. On Day 6, skin samples were biopsied for ribonucleic acid extraction and gene expression assays run for 107 genes of interest. Twenty patients with chronic wounds were randomized to receive standard wound care ± laser therapy 3 times weekly for 4 weeks, and wounds were analysed for healing.

Results

The laser altered expression of 45 genes. Highly up-regulated genes (>5-fold change) included those implicated in wound healing and antiaging, whereas highly down-regulated genes included those implicated in inflammation and extracellular matrix integrity. The LED device altered expression of only 1 gene relative to negative controls. The laser reduced mean wound area by 78% and healed 4 of 10 wounds completely. In contrast, 8 of 10 of those receiving standard care exhibited no change.

Conclusions

A proprietary near-infrared laser exhibited superior ability to influence gene expression in healthy skin than an equivalent LED device and induced the healing of chronic wounds.

Level of Evidence:

Photobiomodulation (PBM) is a phenomenon characterized by nonthermal epigenetic manipulation of the target cell.¹ This is achieved by inducing the cell to a high-energy state through the absorption of red and near infrared (NIR) light energy by cytochrome c oxidase of the oxygen transport chain and the subsequent enhancement of ATP synthesis in cellular mitochondria^2-5 and mitochondrial signal transduction.⁶ Modulation of the intracellular stress response by metabolism of reactive oxygen species is also believed to play a role.^5,7

The phenomenon was first observed by Mester et al at Semmelweis University, Hungary, in the 1960s.⁸ Subsequently, the ability of red laser light to enhance wound healing in a rat model was observed.⁹ It was many years, however, before the mechanisms explaining this phenomenon were unraveled and work continues refining the theory to this day.¹⁰ Presently, the ability of low level red and NIR laser therapy (sometimes known as LLLT) to enhance wound healing in experimental models is well established.¹¹ However, even though much of the preclinical evidence for PBM is based on laser light, light-emitting diode (LED)-based light forms the mainstay of clinical studies owing to the lack of commercially available lasers for use in nonclinical settings.¹² LED technology was developed around the same time as the discovery of PBM and served as substitute for laser light in clinical studies as the technology could produce quasi-monochromatic light cheaply, safely and over a wide surface area simultaneously.¹³ The theoretical basis for substituting laser light with LED was the view that because cytochrome c oxidase was a chromophore for red/NIR light, then by inference the key determinant of the efficacy in PBM therapy was the wavelength of the light source.¹⁴ The reality is more complex. Monochromaticity is only one of several unique features of electromagnetic waves produced by lasers. In addition to wavelength, power, irradiance (power density), and pulse structure are variables shared between laser and LED light, whereas narrow spectral distribution, collimation, temporal and spatial coherence, and polarization are features unique to laser light. When electromagnetic waves travel through a medium, they encounter molecules and they can be reflected, transmitted, refracted, absorbed, diffracted, or scattered.¹⁵ It has been argued that some properties unique to laser light contribute to the photobiomodulatory response in target tissue, either directly because of the effect of absorption of electromagnetic energy on the target or indirectly, because of different properties of reflection, transmission, refraction, diffraction, and scatter.^16,17 This debate continues. What is clear is that in the PBM literature, there remains a dichotomy, with preclinical evidence of enhanced wound healing generated mainly using red and NIR laser light, and clinical studies of aesthetic skin rejuvenation and the treatment of radiotherapy-induced oral mucositis generated mainly using red and NIR LED.^11,12 With the recent development of a proprietary, safe NIR laser for nonclinical use, there is now an urgent, unmet need to establish the clinical role of lasers in PBM and to examine the relative efficacy compared with commercially available LED devices.

A proprietary NIR laser has been developed for use in both nonclinical and clinic settings (LYMA Life Ltd, London, United Kingdom). This device delivers light at 808 nm and 500 mW (a 1500 mW version is also available) and has been rendered safe by utilising the scatter phenomenon to diffuse the beam without altering coherence. The purpose of this study was to evaluate the effect of this NIR laser device on human skin by evaluating gene expression profile relative to a leading commercially available LED device and to bridge the evidence gap between the theoretical and clinical applications of this technology by examining the wound-healing potential of the device in practice.

METHODS

Preclinical Study

Discarded postabdominoplasty human skin from a consented 43-year-old female (Fitzpatrick Type III) underwent excision of the subcutaneous fat within 4 h of surgery. The full thickness skin was excised to nine 4 × 4 cm² samples and transferred to individual petri dishes containing 10 mL cornification medium with antibiotics but without steroids. Tissues were incubated at 37 °C in 5% CO₂, 95% humidity. At time zero, at 24 h and each 24 h thereafter to Day 5, the samples were washed in phosphate-buffered saline, dried, then exposed to the following protocol:

NIR LED (810 ± 3 nm, 5 W [approximate], exposure time 180 s, approximate total energy 56 J/cm²) × 3
NIR laser (808 nm, 500 mW, exposure time 180 s, approximate total energy 5.6 J/cm²) × 3
Negative control (laser not switched on) × 3

The relative properties of the laser and LED light sources used in this study are compared in Table 1. Because the laser is recommended for use with a proprietary skincare formulation (LYMA Life Ltd), Cohort 2 was preprepared using this formulation. After each exposure, the incubating medium was changed, and the samples returned to the incubator. On Day 6, a 10 mm punch biopsy was harvested from the centre of the skin sample and stored at −80 °C until ribonucleic acid (RNA) extraction was performed. All RNA extractions were undertaken using a RNeasy Mini Kit (Qiagen Diagnostics GmbH, Hilden, Germany) following the manufacturer's instructions. Briefly, RNA concentration and purity were determined using a nanodrop 2000 spectrophotometer confirming sample purity (Supplemental Table 1). Copy deoxyribonucleic acid (cDNA) was generated from 100 ng of RNA using a superscript Vilo RT kit and a custom primer pool (Thermo Fisher Scientific Inc., Waltham, MA) as per manufacturer's instructions. cDNA samples were preamplified for 12 cycles and diluted 1:20 with 1×TE buffer for quantitative polymerase chain reaction (qPCR) processing. qPCR was run in the Open Assay format using validated Taqman gene assays in a Life Technologies QuantStudio 12K flex instrument (Thermo Fisher). Each gene was assayed in duplicate. Endogenous control genes selected included glyceraldehyde-3-phosphate dehydrogenase, β-glucuronidase, hypoxanthine phosphoribosyltransferase-1, peptidylprolyl isomerase-A (PPIA), and ubiquitin-C. Based on the stability scores, PPIA was chosen as the control gene (Supplemental Table 2). Data quality and statistical analyses were performed using Thermo Fisher Connect software. Microsoft Excel (Microsoft Corporation Inc., Redmond, WA) was used to analyse these data. Unpaired t-tests were performed (relative to PPIA) to establish P-values, whereas linear respiratory quotient values and linear fold change values were also calculated. Additionally, 3 genes on the panel showed poor quality amplification (tropoelastin, interleukin [IL]-23A, and colony stimulating factor-2), and these were excluded from further analyses. A 1.5 times fold-change in gene expression was considered significant as this is the industry standard.

Table 1.

A Comparison of the Properties of Laser vs LED Light Used in the Study

	Laser	LED	Implication
Power (mW)	500	5000	Laser requires less power than LED as energy transfer is more efficient
Fluence (energy density J/cm²)	5.6	56	In line with clinical recommendations
Wavelength	808 nm	810 ± 3 nm	Chromophore is cytochrome c oxidase
Collimation	Yes	No	Safety diffuser in proprietary laser device de-collimates laser beam rendering it safe
Coherence (temporal)	Yes	No	Laser: constructive interference amplifies the energy carried by the wave LED: destructive interference diminishes the energy carried by the wave
Coherence (spatial)	Yes	No	Laser: retention of potential for constructive interference as light passes through reflective medium (speckle phenomenon) LED: no potential for constructive interference as light passes through reflective medium (no speckle phenomenon)
Directionality	Unidirectional	Multidirectional	Energy transfer more focused, where light energy is unidirectional
Polarization	Yes	No	Polarization may be significant in photobiomodulation but clinical implications uncertain at present

Clinical Study

Participants

The study was conducted at the Hungarian Military Hospital, Budapest, Hungary, European Union. For this Phase 1 clinical trial, a total of 20 consecutive patients with nonhealing wounds were recruited over a period of 6 months between June and December 2023. A nonhealing wound was defined as a wound which had failed to exhibit a predictable pattern of healing within an acceptable time frame and had thus become chronic. All wounds were at least 6 weeks old. Nonhealing wounds included pressure ulcers, diabetic foot ulcers, and stumps following amputation for peripheral vascular disease. All co-morbidities were permissible. There were no exclusions. Patients were randomized (by simple coin toss) to receive standard wound care by way of 3 times weekly dressings alone (Cohort 1) or standard wound care by way of 3 times weekly dressings with NIR laser therapy for 3 min at each dressing change (for a total of 12 NIR laser exposures). At each dressing change, the wounds were gently cleaned with saline, evaluated by way of measurements of the dimensions of the wound as well as assessments of the clinical features of inflammation at the wound edge and wound depth, then dressed with a paraffin-impregnated nonadherent mesh dressing or silicone mesh dressing, followed by dressing gauze and crepe or an adherent dressing with absorbable pad as appropriate given the site and dimensions of the wound. The single assessor was blinded as to the treatment cohort. Any safety issues or side effects were noted as per Phase 1 trial methodology. The trial duration was 4 weeks, based on an a priori assessment of the likelihood of observing a difference in the cohorts. Beyond 4 weeks, we surmised that, as each patient may have been better served by further surgery (and thus dressings alone were not necessarily the standard of care), it may not have been appropriate to continue beyond this point.

Ethics

Institutional review board approval from obtained from the Budapest health science council on March 28, 2023, and was registered with the National Centre for Public Health and Pharmacy (Budapest, Hungary; no. OGYEI/8363/2020). All participants gave informed consent for recruitment to the trial.

RESULTS

The preclinical study revealed that exposure of the defatted skin samples to the NIR laser for 180 s/day over 5 consecutive days influenced the expression of 45 of 107 genes tested at Day 6 relative to the negative control samples. Twenty genes were up-regulated, and 25 genes were down-regulated. In contrast, when defatted skin samples were exposed to LED using the same protocol, the differential expression of only one gene relative to the negative control was noted. At this single time point, the magnitude of up-regulation noted ranged from 1.5 × baseline (a 50% change) to over 32 × baseline (over 3000% change). The maximum magnitude of down-regulation was over 50-fold (a reduction in over 98% of baseline). Largely, the genes up-regulated and highly up-regulated were genes encoding for proteins implicated in tissue growth and wound healing, cell replication, antiaging, antioxidation/stress response modulation, and strengthening of the epidermal barrier and dermoepidermal junction. In contrast, the genes down-regulated and highly down-regulated were genes encoding for proteins implicated in the proinflammatory response and extracellular matrix (ECM) maintenance and stability. The results are summarised in Table 2.

Table 2.

Gene Expression Profile Changes Following Skin Sample Exposure to Near-Infrared Laser (808 nm) vs Near-Infrared (810 ± 3 nm) LED

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Gene	Function	LED		Laser
Gene	Function	FC	%C	FC	%C
TXNRD1	Antioxidant/stress response	n.s.	n.s.	32.33	3133^a
HBEGF	Growth factor/wound healing	n.s.	n.s.	31.63^a	3063^a
AHR	Antioxidant/stress response	n.s.	n.s.	6.17^a	517^a
SIRT1	Antiaging	n.s.	n.s.	5.97^a	497^a
VEGFA	Growth factor/wound healing	n.s.	n.s.	5.46^a	445^a
ITGB1	Epidermal barrier	n.s.	n.s.	5.07^a	407^a
PCNA	Cell replication	n.s.	n.s.	5.02^a	402^a
PANK4	Antiaging	n.s.	n.s.	4.97	397
KITLG	Growth factor/cell migration	n.s.	n.s.	4.42	342
HSPG2	Antiaging	n.s.	n.s.	3.95	295
OCLN	Epidermal barrier	n.s.	n.s.	3.54	254
MMP-1	Extracellular matrix breakdown	n.s.	n.s.	3.45	245
TXN	Antioxidant/stress response	n.s.	n.s.	3.45	245
ADAM17	Immune modulation	n.s.	n.s.	3.33	233
POLG1/MDP1	Antiaging	n.s.	n.s.	2.55	155
GSK3B	Cell replication	n.s.	n.s.	2.46	146
NFE2L2	Antioxidant/stress response	n.s.	n.s.	2.27	127
DSG3	Stability of dermoepidermal junction	1.53	53	2.00	100
KRT14	Keratinocyte stability	n.s.	n.s.	1.81	81
MFN2	Mitochondrial function	n.s.	n.s.	1.5	50
TNF	Proinflammatory cytokine	−1.36	−26	n.s.	n.s.
SERPINH1	Fibrosis/scarring	n.s.	n.s.	−1.63	−39
IL-1B	Proinflammatory cytokine	n.s.	n.s.	−1.79	−44
COL17A1	Extracellular matrix integrity	n.s.	n.s.	−2.04	−51
COL7A1	Extracellular matrix integrity	n.s.	n.s.	−2.68	−63
PTGS2/COX-2	Inflammation	n.s.	n.s.	−2.76	−64
ICAM1	Immune modulation	n.s.	n.s.	−3.02	67
NMRK1	Antiaging	n.s.	n.s.	−3.62	−72
SOD2	Antioxidant/stress response	n.s.	n.s.	−3.61	−72
HAS2	Glycosaminoglycans of extracellular matrix	n.s.	n.s.	−3.82	−74
COL3A1	Extracellular matrix integrity	n.s.	n.s.	−4.61	−78
MMP-2	Extracellular matrix breakdown	n.s.	n.s.	−4.85	−79
PKP1	Intracellular function	n.s.	n.s.	−4.72	−79
KRT5	Epidermal keratin	n.s.	n.s.	−5.32^a	−81^a
PTGS1/COX-1	Inflammation	n.s.	n.s.	−5.41^a	−82^a
SPINK5	Extracellular matrix breakdown	n.s.	n.s.	−6.76^a	−85^a
FBN1	Extracellular matrix integrity	n.s.	n.s.	−7.75^a	−87^a
IL-6	Proinflammatory cytokine	n.s.	n.s.	−8.00^a	−88^a
COL4A2	Extracellular matrix integrity

Clinical Study: The Use of a Proprietary Near-Infrared Laser to Enhance Wound Healing