Statistical analysis. Statistical analyses were conducted using Stata version 15.1 (StataCorp. Stata statistical software: Release 15.1. College Station, TX: Stata Corporation, Texas, USA, 2017). For continuous data between two groups, an independent t-test was performed for parametric distribution, while the Mann-Whitney U test was employed for non-parametric distribution. Repeated measures ANOVA was utilized to assess the repeated measurements of dependent outcomes. Categorical data were analyzed using either the Chi-square test or the Fisher’s exact test. All statistical analyses were two-tailed. A significance level of 0.05 was employed to calculate proportions and 95 percent confidence intervals.

Moreover, the optimal treatment parameters, such as energy levels, density and treatment intervals, should be determined. Additionally, the applicators for delivering energy to the scalp needed to be explored with thorough assessment of this combined laser therapy and topical medications, e.g. minoxidil and PRP. It would also be beneficial to compare this therapy with control groups or alternative laser technologies, while extending the duration of follow-up periods.

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Evaluation. Assessment by two dermatologists was based on the interpretation of photographs before and after treatment using a 7-point global assessment scale as an expert panel assessment score15 of significantly decreased (-3), moderately decreased (-2), slightly decreased (-1), no change(0), slightly increased (+1), moderately increased (+2) and significantly increased (+3). The two independent physicians were blinded to treatment protocol and method. All patients also scored their satisfaction with the overall treatment outcome using the 7-point scale as previously described. At each visit, medical examination and adverse effects related to laser treatment, including pain, erythema, erosion, oedema, seborrheic dermatitis, dryness, pruritus, and broken hair shaft, were registered at any time. The pain score was evaluated after every treatment. The trichoscopic examination had been evaluated at the point of intersection between mid-sagittal and coronal line connecting tragus of ears and 2 cm anterior to that point.

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Adverse effects. There were no local adverse reactions. The pain score was minimal (1-2 of 10) and it could be resolved in 15 to 30 minutes. There were few petechiae at the scalp and no breakage of the hair shaft after irradiation treatment. No pruritus, dryness, dandruff, folliculitis, eczematous or scaly was observed throughout the follow-up.

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Keywords: Androgenetic Alopecia, 1064-nm Picosecond Laser, Fractional Picosecond laser, Fractional Laser Therapy, Laser-Induced Optical Breakdown (LIOB), Hair Loss Treatment

Limitations. This was an initial pilot investigation. Therefore, further research is crucial to validate the effectiveness of picosecond laser therapy in promoting hair regrowth, with a designed controlled randomized trials in human participants towards more understanding of the mechanisms underlying this therapy.

Clinical evaluation. The expert panel photographic assessment at one month after last treatment for 5/5 (100%) of cases with clinical response (score ≥ 1) and 2/5 (40%) of cases with excellent improvement (score = +3) at four months. A significant clinical improvement was observed from 1 to 4 months after the treatment when compared to the baseline, with expert panel assessment score (mean + SD) of 1.0, 1± 0.45, 1.9 ± 0.22, 2.2 ± 0.27 (p<0.001), respectively. (Figure 2 and Table 1)

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ABSTRACT: Background. There are limitations and side effects of currently approved treatments for AGA, such as topical minoxidil, oral finasteride, and low-level light therapy.

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Objective. This study aimed to investigate the potential of fractional picosecond laser (FPL) therapy for promoting hair regrowth.

There are currently specific fractional laser therapies, such as 1550-nm nonablative fractional erbium-glass laser,5,6 ablative fractional 2940-nm erbium:YAG laser,7, 8 and ablative fractional CO₂ laser,9 implicating the improvement of skin laxity, acne scarring, fine wrinkles, and photoaging. Moreover, literature reviews demonstrate the effectiveness of fractional lasers on hair regrowth10 and recurrent hair loss prevention.11 Fractional lasers, with selective photo thermolysis effects, induce hair growth when restricted to appropriate settings. This cutaneous wound healing process increases tremendously during the anagen stage of hair cycle and additional hair follicle regrowth after wounding.11 The combination therapy with agents, such as minoxidil12 and platelet rich plasma (PRP),13 may also produce a synergistic effect in hair growth stimulation.

Conclusion. The preliminary study demonstrates the potential of 1064-nm FPL for promoting hair regrowth in male pattern hair loss. Nonetheless, further research is recommended to elucidate and ratify for the optimization of this promising treatment approach.

There was an animal model study to explain the mechanism of FPL in hair growth. It suggested that a fractional 1064-nm picosecond Nd:YAG laser could promote different hair regrowth based on petechiae formation from capillary leakage, more pronounced in laser-treated areas, and proportional to fluence level from LIOB.17 Petechiae is related to wound healing and hair regrowth through growth factors from platelet leakage. The increase of vascular endothelial growth factor (VEGF)18 and angiogenesis19 is related to active regrowth of hair.  Moreover, there is a high Wnt/β-catenin signaling in the wounded areas.20 After wound healing, hair growth and modulation of hair cycle are promoted by using the fractional photo thermolysis laser. It is the earliest molecular pathway to positively regulate hair follicle initiation. Thus, the Wnt/b-catenin pathway with increasing Wnt 5a [beta]-catenin signals could lead to higher anagen conversion of hair.5

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There were five male participants (mean + age = 42.3 ± 9.8 years) with mild-to-moderate AGA who completed the study. The age of AGA onset and duration of AGA were 38.5 ± 10.6 and 5.5 ± 2.3 years, respectively. All of the subjects had previous treatment with minoxidil solution or oral finasteride.

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The optimal clinical endpoint was very mild erythema with minimal acceptable pinpoint bleeding. During the laser treatment, a cooling device was used. Patients were scheduled for treatment three times at 4-week intervals, with follow-up at 4 weeks post-procedure. Shampooing, warm baths, and hard physical exercise were prohibited for 12 hours after the laser treatment. Application of topical agent or administration of any medications was not permitted prior to the study recruitment for six months and during the course of investigation.

Methods. This was a pilot study in which five male participants were treated with a 1064-nm FPL for mild-to-moderate AGA. The patients underwent three treatments at four-week intervals, followed by a four-week post-procedure assessment. Expert panel assessment score and patient satisfaction was assessed using a seven-point scale. Dermoscopic analysis was conducted to evaluate hair shafts. Adverse effects were also monitored.

Results. Clinical improvement was observed at 1 to 4 months after treatment, with a significant increase in expert panel assessment scores (p<0.001). Patient satisfaction with hair density and thickness also improved significantly at 1 and 4 months (p=0.038 and p=0.007, respectively). Adverse effects were minimal and resolved within a week. Dermoscopic analysis showed minimal petechiae with no hair shaft damage.

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The benefits of using FPL for hair loss treatment are evident in laser induced plasma formation to stimulate the production of collagen without causing any wounds. Our technique for collagen remodeling could ensure the avoidance of damage in skin layers due to limited micro explosions into a small volume within the treated areas. As a result, larger portions of collagen were effectively treated following a risk of severe side effects and no report of unpleasant sensations during or after treatment. The treatment was very acceptable to all subjects. No anesthesia, cooling plate, or other topical applications were needed before, during, or after the treatment.

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Patient satisfaction. Patient satisfaction with hair density and hair thickness after laser treatment yielded significant improvement when compared to the baseline for 60 percent (p=0.038) and 100 percent (p=0.007) improvement at 1 and 4 months, respectively (Figure 3).

Many trials have been conducted for the management of androgenetic alopecia (AGA). There are limitations to the efficacy of and side effects associated with the currently approved therapies, including topical minoxidil, oral finasteride, and low-level light therapy.1,2–4

This pilot study reported the efficacy of 1064-nm FPL on hair regrowth promotion, which was generally well-tolerated and no topical anesthesia. The innovative minimally invasive FPL (almost minimal pain and no downtime) is easy to perform, using laser-induced optical breakdown (LIOB), for lesions exclusively in the treated dermal areas.16 The 1064-nm FPL could be preferably for treatment of alopecia without damaging the preexisting hair shafts and causing no epidermal ulceration owing to its non-ablative nature.

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The fractional picosecond laser (FPL), a novel non-thermal technology utilizing laser-induced optical breakdown (LIOB),14 is for skin rejuvenation and acne scar treatment to maintain epidermal integrity and generate microscopic intradermal lesions. It also prompts a wound healing response, new collagen formation, and subsequent skin remodeling, with rejuvenation effects and no open wounds. Whereas, the prevailing laser devices rely on selective photo thermolysis and linear absorption by skin constituents. Thus, the FPL inducing LIOB holds potential for hair growth promotion. This study aims to report the effectiveness of a 1064-nm FPL in hair regrowth for male AGA.

The method known as laser induced breakdown (LIOB) is fundamentally different from the laser technique for skin rejuvenation. Unlike the devices based on optical energy absorption, LIOB involves nonlinear processes of absorption particularly when exposed to high levels of irradiance. This results in the creation of electron density11 to generate plasma through multiphoton and avalanche ionization, leading to vaporization and expansion within the layer.13,14 The concentrated energy produces localized effects to micro explosions in the skin. 10,15 Studies on skin treatment demonstrate that this approach could effectively stimulate the formation of new collagen for microscopic intradermal lesions, while keeping the outermost layer of skin intact. Importantly, this treatment does not cause any wounds, changes in pigmentation scarring, or adverse effects. Furthermore, participants report no discomfort during or after the procedure, with acceptability.

This was a pilot pre- and post-therapeutic study. The skin was prepared with a disinfecting agent. No topical anesthesia was used prior to laser treatment. The hair thinning area on the scalp was treated with standardized parameters in all participants as follows: the fractional Nd: YAG 1064-nm picosecond laser with fractional lens array (DiscoveryPICO®; QuantaSystem, S.p.A., Samarate (VA), Italy) with spot size of 8 mm, fluence of 0.06 J/cm2 (from the minimal scalp reaction, no hair shaft brakeage and acceptable pain score), and frequency of 10 Hz for 3-4 passes. (Figure 1) The device was equipped with a specialized handpiece of micro-lens array (MLA) to fractionate the laser beam into 66 microbeams in an 8 mm circular diameter, covering 5 percent of the treatment spot in total and distance between each microdots of 1 mm (dots pitch).14

The FPL, based on laser-induced optical breakdown (LIOB), demonstrates its potential for promoting hair growth without causing damage to existing hair or epidermal ulceration. The mechanism may involve petechiae formation, which contributes to wound healing and growth factor release, along with heightened Wnt/β-catenin signaling. The treatment was well-tolerated, with minimal pain and high patient satisfaction.

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The 1064-nm FPL, a novel minimally invasive laser technology inducing LIOB, is beneficial for hair growth promotion without damaging the preexisting hair shafts and causing epidermal ulceration. The hair regrowth based on the principle of LIOB creates wound healing process, leading to hair regeneration. Ultimately, 1064-nm FPL can be potential as an alternative treatment for patients with hair loss. Further studies are recommended to elucidate and verify the efficacy of this technique.

Dr. Lueangarun is with the Department of Anti-Aging and Regenerative Medicine Medicine, College of Integrative Medicine at Dhurakij Pundit University in Bangkok, Thailand, and the Division of Dermatology at the DeMed Clinic Center in Bangkok, Thailand. Dr. Tempark is with the Department of Pediatrics and Faculty of Medicine at King Chulalongkorn Memorial Hospital at Chulalongkorn University in Bangkok, Thailand.

In practice, the lowest fluence of FPL parameter setting is applied with minimal passes to make patient comfortable and create LIOB without bleeding pain or hair shaft damage. Impressively, there is an improvement of clinical response with almost no pain and high patient satisfaction.

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