Advancements in non-laser energy-based devices in trichology: A comprehensive review

INTRODUCTION

The field of trichology has witnessed significant advancements in non-invasive techniques that help in hair growth promotion, especially in conditions such as androgenetic alopecia (AGA), female pattern hair loss (FPHL), alopecia areata (AA), chronic telogen effluvium, and management of unwanted hair in conditions such as hirsutism and hypertrichosis. Low-level light therapy is an established method and remains the only food and drug administration (FDA)-approved treatment for AGA. In addition, several non-laser approaches are employed, including iontophoresis, electrotrichogenesis (ETG), intense pulsed light (IPL), scalp cooling therapy, photodynamic therapy (PDT), radio-frequency (RF) technology, oxygen therapy, and ultrasound [Figure 1]. This article emphasizes the importance of non-laser techniques used in various indications in trichology.

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Figure 1:

Non-laser devices in trichology. (a) Electrotherapy; (b) iontophoresis; (c) photodynamic therapy; (d) oxygen therapy; (e) intense pulsed light; (f) ultrasound; and (g) radiofrequency. Radiofrequency image courtesy: Dr. M Ramesh, Department of Dermatology, Kempegowda Institute of Medical Sciences Hospital, Krishna Rajendra Road, Visveswarapura Puram, Bangalore, India.

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A systematic literature search was conducted in databases such as PubMed and Google Scholar on non-laser methods in trichology, mainly focused on drug delivery, stimulating hair growth, preventing chemotherapy-induced alopecia (CIA), and reducing unwanted hair [Table 1].

IONTOPHORESIS

Iontophoresis is a specialized drug delivery technique that utilizes low electrical current to transport a drug into and through the skin. This method enhances the absorption of drugs, particularly uncharged molecules through the electroosmosis process. Hair follicles, which extend deep into the dermis, provide a transappendegeal pathway with lower resistance compared to the stratum corneum, enabling deeper and more effective drug absorption.

Iontophoresis has been used in transporting various therapeutic agents. Studies have demonstrated its efficacy in delivering drugs such as minoxidil sulfate (MXS), chitosan nanoparticles loaded with MXS, and growth factor cocktails to treat conditions like androgenic alopecia.^1-5 These agents are effectively targeted to specific sites within the skin, enhancing treatment outcomes while minimizing systemic side effects.

The application of a small electrical current causes ions of the drug to migrate through the skin, driven either by anodal or cathodal stimulation. This process induces muscular stress, enhancing the contractile capacity, dilation of pores and facilitating the absorption of the active ingredients.⁶ These mechanisms significantly improve the absorption of active ingredients into the targeted areas, such as hair follicles and follicular infundibula.¹

Recent advancements in iontophoresis device technology have focused on improving usability, effectiveness, and patient comfort. Wei et al.⁷ designed a portable drug delivery device for treating AGA. This device includes a drug container, an iontophoretic stimulation part, and a rechargeable part which performed well and enhanced drug delivery. Effective drug penetration through iontophoresis has been demonstrated, with a synergistic effect of combining iontophoresis with sonophoresis, showing ×10 enhancement in transdermal drug penetration in Franz-type cells and hairless mouse skin.⁸ To address discomfort and attachment difficulties caused by common metal electrodes, Wei et al. designed a carbon-silicon electrode.⁹ This electrode reduces pain, increases conductance, and improves hair coverage by allowing hair to be voided for attachment. Ongoing research continues to refine these devices, aiming to optimize functionality and safety while expanding their applicability in clinical settings. The clinical studies on iontophoresis are summarized in Table 2.

ETG/ELECTROTHERAPY

ETG is a method that enhances the influx of calcium ions into dermal papilla cells through voltage-gated transmembrane ion channels. This mechanism facilitates ATP synthesis in mitochondria, activates protein kinases, and stimulates protein synthesis and cell division. The overall effect of ETG is thought to regulate the secretion of various hair growth factors, promote the proliferation of hair follicles, extend the anagen stage, and ultimately contribute to the regeneration of hair. It is a non-invasive, physically-based approach that plays a crucial role in regenerative tissue engineering through the application of alternating electric fields.¹⁰ Various studies explore the efficacy of electrical stimulation (ES) methods. The use of pulsed electrical fields (PEFs) in promoting hair regrowth has gained significant attention in recent studies. Maddin et al.¹¹ reported a remarkable 66.1% increase in hair count over 36 weeks, attributing this effect to the electrophysiological impact on quiescent hair follicles and increased cell mitosis. Furthermore, the application of pulsed electrostatic fields, known as ETG, in breast cancer patients undergoing chemotherapy exhibited promising results in hair retention, suggesting potential improvements in treatment compliance and psychosocial well-being.¹² However, despite promising results, ETG awaits approval from the US Food and Drug Administration, necessitating further randomized double-blind trials.¹³

Khan et al.¹⁴ explored the use of PEF to stimulate hair follicles, demonstrating a significant increase in anagen follicles following treatment in Sprague–Dawley rats. Another innovative approach involves the self-powered omnidirectional motion-activated and electric stimulation device (m-ESD), a universal wearable device designed to harness random body motions for hair regeneration.¹⁰ The m-ESD showcased impressive outcomes, including longer and denser hair after 3 weeks compared to conventional treatments such as minoxidil (Mx), Vitamin D3, and normal saline. This nonpharmacological, self-powered wearable device not only accelerated hair growth but also addressed genetic keratin disorders, offering a promising solution for hair loss.

Hwang et al.¹⁵ investigated the potential of micro-current ES in promoting hair regrowth by applying it to human hair follicle-derived papilla cells. The study revealed promising results, including enhanced cell proliferation, migration, and modulation of cell cycle progression. In addition, Yan et al.¹⁶ explored ES with a PPy-modified electrode upregulated trichogenic gene expression in human dermal papilla cells (hDPCs), which increased gene expression and the number of hairs in cells of the transplanted mice (with ES) compared to untreated cells (without ES).

These studies provide valuable insights into nonpharmacological approaches for hair regenerative medicine; further investigations are warranted to establish the long-term efficacy and viability of these techniques, particularly in clinical applications for various types of hair loss. Table 3 presents a comprehensive overview of various studies on the effectiveness of electrical stimulation methods in promoting hair growth.

SCALP COOLING

Scalp cooling therapy has emerged as a pivotal preventive measure against CIA for cancer patients. Developed in the 1970s, this globally adopted technique utilizes vasoconstriction and hypothermia to minimize blood flow and drug uptake by hair follicles, demonstrating consistent efficacy with success rates averaging 50–70% over the past two decades.¹⁷

The cornerstone of this therapy is a sophisticated, self-contained, and electrically powered refrigeration unit. This unit circulates a glycol-based fluid through channels within a cap, enabling precise control and maintenance of scalp temperature throughout the treatment course. The cap is equipped with sensors strategically placed at the front and back to monitor scalp temperature, with an additional sensor preventing temperatures from dropping below freezing. Any deviations from the default temperature range are promptly identified and corrected by the feedback loop established through the sensors. This closed-loop system ensures real-time monitoring and intervention, guaranteeing that the scalp temperature is maintained within the optimal range of 3–5°C throughout the entire treatment process.^18,19 Scalp cooling therapy has gained widespread acceptance, being implemented in over 30 countries.²⁰ Its consistent success rates and the technological advancements incorporated into the device underscore its relevance in contemporary cancer care.¹⁷

CIA is a distressing side effect of cancer therapy that impacts the emotional well-being of patients. Several studies have explored the effectiveness and safety of scalp-cooling devices in preventing or minimizing hair loss during chemotherapy. A prospective observational study conducted by Kate et al.²¹ demonstrated that scalp-cooling devices were particularly effective in reducing CIA in patients treated with taxane-based chemotherapy compared to anthracyclines. The study, involving 100 patients, reported minimal adverse events (AEs), highlighting the safety of these devices.

Bülow et al.²² further delved into the relationship between subcutaneous temperature and hair preservation. Their findings suggested that maintaining subcutaneous temperatures below 22°C with scalp cooling techniques could prevent hair loss, attributing the success to the metabolic effects of the process. This metabolic impact was reinforced by a more recent study conducted by Carbognin et al.,²³ who reported a 68.0% success rate in preventing alopecia in breast cancer patients with varying chemotherapy regimens.

A randomized clinical trial by Nangia et al.²⁴ involving 182 women with breast cancer provided robust evidence supporting the efficacy of scalp cooling. The study demonstrated a 50% significant reduction of hair loss with scalp cooling. Similarly, a study in Italian oncology units by Gianotti et al.²⁵ involving 220 female breast cancer patients undergoing curative chemotherapy reported a 68% success rate in scalp cooling, with high rates of success in both taxane-based and combined anthracyclines and taxanes chemotherapy.

The comprehensive review by Wim et al. (2011)²⁷ synthesized findings from 58 scalp cooling publications, emphasizing the reversibility of CIA in many chemotherapy regimens and its cost-effectiveness. The article called for further research on scalp cooling methods and advocated for its accessibility in all hospitals for suitable patients.

While safety concerns and the potential for scalp metastases limit the utilization of scalp cooling use in the US, recent research, as highlighted by Kruse and Abraham,²⁸ has demonstrated its effectiveness, especially with taxane-based chemotherapy. However, logistical challenges such as device availability and insurance coverage remain hurdles that need to be addressed for widespread adoption.

The reviewed studies collectively suggest that scalp-cooling devices are effective in preventing or reducing CIA, with encouraging success rates and minimal AEs reported [Table 4]. Further research and efforts to overcome logistical challenges are necessary to make this approach widely available, ensuring it becomes an integral component of holistic cancer care.

PDT AND MICRONEEDLING

PDT is a novel approach involving the application of a topical photosensitizer, exposure to light, and oxygen to eliminate damaged cells, leaving normal skin unaffected selectively.²⁹ In a study targeting static AA, PDT was administered to six patients who had previously undergone unsuccessful treatments. Despite limited overall success, one patient experienced complete regrowth after four sessions, particularly notable in AA of the beard, an area not previously explored with PDT. This suggests a potential differential response in beard hair AA, warranting further investigation.³⁰

AGA, characterized by hereditary hair loss, traditionally relies on pharmaceuticals and, of late, various regenerative medicine applications for treatment. A study using red laser light, blue light-emitting diode (LED) light, and a photo cosmetic product called photoactive showed enhanced hair growth in AGA, reducing the need for professional treatments and promoting hair reconstruction.³¹ Another investigation using mice skin tissues explored a low-cost PDT system for laser-assisted hair removal. The study revealed that methylene blue selectively absorbed by hair follicles, coupled with a low-power continuous-wave helium-neon laser, successfully damaged hair follicles, offering a more promising outcome compared to traditional laser-mediated methods.³²

In the context of moderate to severe AA, a therapeutic combination of PDT with 5-aminolevulinic acid (ALA) and microneedling demonstrated efficacy in a study involving 41 patients. The synergistic approach yielded complete hair regrowth in some cases and improvement in others, providing a potential avenue for AA treatment.³³

However, not all studies have reported positive outcomes. A pilot study utilizing a microneedle roller to enhance the trans-epidermal drug delivery system for treating AA did not result in hair growth or changes in histologic findings. This suggests that the effectiveness of PDT for AA may vary and necessitates further exploration with different parameters.³⁴

Similarly, the combination of microneedle treatment system (MTS) and methyl 5-aminolevulinic acid-PDT for extensive AA did not yield positive results in a study involving six patients. Despite prior resistance to conventional therapies, none of the patients achieved hair regrowth in either the MTS or non-MTS areas. The study underscores the need for additional investigations with varied drug-delivery systems and in-depth microscopic analysis.³⁵

Finally, in a randomized clinical study evaluating the efficacy and safety of ALA-PDT for AGA, the treatment was found to be safe and tolerable. However, no significant difference in hair density was observed between the ALA-PDT-treated and red-light therapy-treated halves of the scalp. This suggests the need for further research to determine the efficacy of ALAPDT as a viable treatment option for AGA.³⁶

In conclusion, while PDT shows promise in addressing various forms of hair loss, the outcomes vary across different conditions and treatment modalities. Further research is crucial to refine protocols, understand optimal parameters, and establish the effectiveness of PDT in specific types of alopecia.

RF

RF devices generate an electric current within an electromagnetic field with a frequency ranging from 3 kHz to 300 mHz. Once the current reaches tissue, it encounters the tissue impedance, resulting in the conversion of electric energy to heat energy. The generated energy depends on the energy flowing through the impedance of the target tissue. RF devices are classified as monopolar (single electrode tip) and bipolar (two electrodes applied to the skin).³⁷ Studies have explored various RF modalities such as bipolar, monopolar, and microneedling RF, highlighting their efficacy and safety for different treatments.³⁸

USE OF RF IN HAIR REMOVAL

Elos technology combines bipolar RF with optical energy (e.g., lasers or IPL) for effective hair removal. The optical energy targets melanin in the hair shaft, converting it into heat, while the RF energy emits heat to the surrounding tissue, further heating the hair follicle. This combination allows for lower levels of both energies, making the treatment safer and more comfortable. The synergy between optical and RF energy ensures better destruction of hair follicles, effectively reducing hair growth and making the treatment suitable for various skin types and hair colors. Kincaid et al.⁴⁹ mentioned the utility of bipolar and monopolar RF devices for effective hair removal. Studies emphasize the promising outcomes achieved by combining bipolar RF with IPL, showcasing long-term removal of body and facial hair. The chromophore-independent energy delivery of RF renders it suitable for treating lighter-colored hair and individuals with darker Fitzpatrick skin types.⁴⁹

USE OF RF IN HAIR GROWTH

RF can also stimulate hair growth on its own. RF energy increases blood flow to the scalp, enhancing the delivery of nutrients and oxygen to hair follicles, which promotes healthier and stronger hair growth. It also stimulates collagen and elastin production, strengthening hair follicles and improving scalp health.

Microneedling RF involves penetrating the skin and releasing RF currents from needle tips, creating RF thermal zones (RFTZ) in the dermis without damaging the epidermis. This process induces thermal and mechanical injury, releasing of releasing growth factors and activating stem cells, contributing to hair regeneration. Studies indicate that RF exposure induces the expression of insulin-like growth factor-1 in dermal papilla cells, promoting hair growth.⁵⁰ Further research includes RF-based treatments for conditions such as eyelash regrowth,⁵¹ AGA,⁵² FPHL,⁵³ and male pattern hair loss,⁵⁴ highlighting the potential of RF in enhancing hair regrowth and hair health. The key findings of RF studies are summarized in Table 5.

In summary, RF technology in dermatology has gained significant attention for its dual capabilities in both hair removal and hair growth, depending on the specific RF modality employed.

OXYGEN THERAPY

Oxygen therapy focuses on delivering pure oxygen to the dermis and epidermal layers through devices such as the X2 Exea. These devices allow the flow of up to 96% pure oxygen to reach the skin’s superficial layers, aiding absorption by the dermis and epidermis. Oxygen supply becomes crucial for hDPCs, which are vital for hair growth and regeneration. Park et al.⁵⁵ propose that continuous oxygen supply is essential for hDPC survival and regrowth, particularly during periods of oxygen deficiency, suggesting potential benefits for addressing hair loss. A nanoemulsion based on perfluorooctyl bromide is highlighted as a tool for sustainable oxygen supply, promoting hDPC growth and gene expression.

PHYSIOLOGICAL EFFECTS OF OXYGEN

Oxygen therapy showcases various physiological effects with potential benefits for hair care. Oxygen is known to enhance cellular metabolism and accelerate healing processes. It exerts anti-inflammatory effects by inhibiting fibroblast apoptosis, decreasing tumor necrosis factor-alpha expression, and inhibiting prostaglandin synthesis. In addition, oxygen promotes neoangiogenesis by releasing vascular endothelial growth factors and other factors. Its antibacterial effect is attributed to the release of reactive oxygen species, which can degrade cellular membranes and eliminate pathogenic microorganisms.

TOPICAL OXYGEN THERAPY FOR HAIR LOSS

Bennardo et al.⁵⁸ explored the use of topical oxygen therapy as an adjuvant treatment for hair loss, evaluating its efficacy in delivering 5% Mx and a phytotherapeutic agent through an oxygen dispenser. Results demonstrated the usefulness of topical oxygen therapy in treating conditions such as AGA and telogen effluvium. The study suggests its potential as an adjuvant therapy, emphasizing the need for further research in larger study groups.

HYPERBARIC OXYGEN THERAPY (HBOT) IN HAIR TRANSPLANTATION

Fan et al.⁵⁹ conducted a study assessing the clinical efficacy of HBOT as an adjuvant treatment for hair transplantation surgery. The results indicated a significant decrease in itching and folliculitis in the HBOT group, along with a lower post-operative shedding rate. Although the survival rate at 9 months showed no significant difference, early post- operative satisfaction was notably higher in the HBOT group. The study provides evidence for the potential of HBOT in minimizing postsurgical follicle shedding and reducing associated discomfort, making it a promising adjuvant therapy in hair transplantation surgery.

In conclusion, oxygen therapy, whether through topical applications or more advanced techniques like HBOT, holds promise in cosmetic and hair care procedures. The physiological effects of oxygen on cellular processes and its potential benefits for promoting hair growth make it an area of interest for further research and development in the field of dermatology and esthetics.

IPL

IPL is a popular non-invasive method for hair reduction and removal, offering versatile and effective solutions for various skin conditions. Light-based technology for hair removal uses selective photothermolysis to target melanin in hair shafts.

A polychromatic IPL device operates in the wavelength range of 400–1200 nm. It is non-coherent, meaning it has a disorganized array through space, and its photobiological reactions are not dependent on the coherence of lasers. The light is non-collimated, diverging randomly in all directions from the upper lamp while progressing. The device has a large spot size, resulting in less scatter and a slower decay of fluence. Notably, a handheld, low-fluence, and home-use IPL device has received FDA approval for the treatment of unwanted facial hair.⁶⁰

Studies have explored the efficacy and safety of IPL devices, targeting different aspects of hair growth and reduction.⁶¹ A study by Dawood et al.⁶² explored the efficacy of an IPL home-use device in women with unwanted facial hair, revealing a substantial average hair reduction of 70.9% after five sessions, with 40% of subjects showing excellent responses. El-Domyati et al.⁶³ delved into the changes in hair follicles in post-IPL, highlighting a decrease in hair count and terminal anagen follicle percentage, suggesting the mechanism involves telogenesis and miniaturization. In a murine model, Jiang et al.⁶⁴ demonstrated that low-fluence IPL promotes hair growth by inducing an earlier transition from telogen to anagen phase and prolonging the anagen phase duration, suggesting its potential as a therapeutic treatment for hair regrowth.

However, challenges arise from the variability of IPL outcomes, as illustrated by a retrospective chart review conducted by Willey et al.⁶⁵ Among 543 patients undergoing laser/IPL photo epilation, 10.49% exhibited increased hair growth, primarily in Alexandrite and IPL devices, with onset occurring between the third and tenth treatments in 71.2% of cases. This emphasizes the need for understanding patient demographics and treatment parameters. On the other hand, El Bedewi⁶⁶ underlined the safety and efficacy of non-coherent IPL for hair removal, with an 80% reduction observed in 210 patients with skin type III-V.

Li et al.⁶⁷ underscored IPL’s two-decade history of successful cosmetic applications and anticipated broader clinical use with improved IPL devices and combined treatments. Furthermore, Hattersley et al.⁶⁸ provided insights into AEs related to home-use IPL devices, revealing skin pain, thermal burn, and erythema as common AEs. This marks a significant contribution to the understanding of IPL safety through post-marketing surveillance.

Table 6 provides a comprehensive summary of key studies, ranging from home-use IPL devices to low-fluence IPL irradiation in mice, shedding light on the diverse applications and outcomes associated with IPL technology in the realm of dermatology and cosmetic treatments.

HIGH-INTENSITY FOCUSSED ULTRASOUND

Ultrasonography has emerged as a promising diagnostic tool in various medical fields, with high-frequency ultrasonography (HF-USG) gaining recognition in dermatological practice, particularly in aesthetic dermatology. This review delves into recent studies exploring the application of ultrasonography in trichology, shedding light on its potential as a non-invasive method for diagnosing and evaluating hair-related conditions.

The study by Mikiel et al.⁶⁹ presents an insightful comparison between trichoscopy and HF-USG in a group of healthy adults. The results indicate that HF-USG can serve as a valuable complement to non-invasive diagnostic procedures, revealing hyperechogenic entrance echoes and well-defined hypoechoic follicular structures. Notably, HF-USG exhibited a higher resolution and broader visualization of follicular structures compared to trichoscopy, showcasing its potential to enhance scalp evaluation.

In the realm of AGA treatment, the integration of ultrasound and drug delivery systems has shown promising results. Liao et al.⁷⁰ developed a biomedical approach utilizing ultrasound contrast agent albumin-shelled microbubbles (MBs) to enhance transdermal delivery of Mx. This innovative approach, involving chitosan oligosaccharide lactate and Mx, not only accelerated drug diffusion but also promoted hair growth while minimizing treatment duration. Further research by Liao et al.⁷¹ expanded on this concept, demonstrating that dual-frequency ultrasound-mediated MB cavitation significantly enhanced Mx delivery and hair growth efficacy both in vitro and in vivo, showcasing the potential for improved treatment outcomes.

In addition, the application of ultrasound in the early detection of Hidradenitis Suppurativa (HS) marks a significant advancement. In a cross-sectional study conducted by Wortsman et al.,⁷² abnormalities in hair follicles were revealed using 70-MHz ultrasound among patients with HS. The ultrasound identified signs such as a connecting band between adjacent hair follicles (known as the bridge sign), a fragment of the hair shaft protruding through a dilated hair follicle (referred to as the sword sign), and the presence of retained cylindrical keratin fragments in the dermis. These findings were correlated with disease severity, underscoring the diagnostic utility of ultrasound in the early detection of HS signs and aiding treatment decisions.

The reviewed studies collectively highlight the promising role of ultrasonography in trichology. From enhancing diagnostic capabilities to improving drug delivery systems for hair-related conditions, ultrasound technologies present exciting possibilities for the future of trichological diagnostics and treatments. As research continues to explore and refine these techniques, ultrasonography may become an indispensable tool in the hands of trichologists, offering precise and noninvasive insights into various hair and scalp conditions.

CONCLUSION

To the best of our knowledge, this is the first review study to discuss a diverse range of advancements in non-invasive techniques in the field of both diagnostic and therapeutic trichology. As technology continues to evolve, further research is essential to refine protocols, establish long-term efficacy, and overcome logistical challenges for widespread adoption. These advancements collectively contribute to a comprehensive understanding of non-invasive interventions in trichology.