[Academic Presentation] Laser Therapy and the Skin Barrier

Article reprinted from: Chinese Journal of Dermatology and Venereology, Issue 01, 2017

Author: Liang Hong, Dai Xing

The skin is the largest organ of the human body, covering the entire body surface and serving as an essential barrier. The stratum corneum, located at the outermost layer of the epidermis, was once thought to be a structure composed of dead, nonfunctional cells. However, recent research has revealed that keratinocytes and their extracellular components are tightly interlocked, forming a permeability barrier for the body. The skin barrier is often likened to a “brick wall”: the keratinocytes serve as the “bricks,” while the intercellular lipids act as the “mortar,” firmly binding the keratinocytes together to maintain a functional skin barrier that prevents water loss while protecting against external insults. In addition, a hydrolipidic film overlies this brick‑and‑mortar structure, working in concert with it to constitute the skin’s physical barrier. Among the applications of laser medicine, the most well‑known and widely used area is laser therapy for skin diseases. During treatment, lasers frequently disrupt the skin’s normal architecture and impair its physiological functions, thereby compromising therapeutic outcomes. This article examines how different modes of laser action affect skin barrier function and its repair, summarized below.

[1] The Impact of Laser Therapy on the Skin Barrier

Due to its unique light-emission mechanism and the distinctive structure of lasers, laser radiation not only exhibits all the properties of ordinary light but also possesses advantages that are unmatched by conventional light sources, thereby finding specialized applications in dermatology. When biological tissues absorb laser energy, a series of energy‑conversion processes may occur: optical energy is transformed into thermal energy, chemical energy, mechanical energy, or internal energy of biomolecules. These physicochemical processes are referred to as laser‑tissue interactions; moreover, the subsequent effects of these factors on biological tissues can lead to morphological and functional changes at the molecular, cellular, and tissue levels. Based on the mode of energy conversion, the interaction between lasers and skin tissues can be classified into three types: photochemical effects, photothermal effects, and photo‑mechanical effects.

1. 1 Photochemical Effect

The photochemical effect, also known as the non-thermal effect, refers to the ability of laser photons to excite specific biomolecules, thereby triggering chemical reactions. Processes such as photosynthesis in green plants, vision in animals, photodegradation of coatings and polymeric materials, and photocatalysis in photography, photolithography, and organic chemical reactions are all closely related to the photochemical effect. Its underlying mechanisms can be summarized in five main aspects: photoisomerization, photosynthesis, photodissociation, and photosensitization; moreover, the biostimulatory effects of lasers also fall under the umbrella of photochemical phenomena. In the medical field, the most widely utilized aspect of the photochemical effect is photosensitization, with photodynamic therapy (PDT) being the most representative application.

The mechanism of action of photodynamic therapy (PDT) involves the photoactivation of a photosensitizer within tissues under aerobic conditions, which, through a series of photochemical reactions, generates large amounts of reactive oxygen species, thereby damaging the target tissue and achieving therapeutic effects. With its precise targeting capabilities, PDT has been widely adopted across various medical disciplines, with primary indications including solid tumors and vascular diseases—such as skin cancers, nasopharyngeal carcinoma, laryngeal cancer, gliomas, lung cancer, bladder cancer, breast cancer, and gastrointestinal malignancies—and vascular disorders like age‑related macular degeneration, esophageal varices, and port-wine stains. PDT also exhibits antimicrobial activity, helping to control dental plaque and improve periodontal disease, as well as treating HPV‑associated conditions such as genital warts. Furthermore, it can be used to manage a range of dermatologic conditions, including acne, photoaging, psoriasis, and porokeratosis.

During PDT treatment, the expression of Toll‑like receptor 2 and Toll‑like receptor 4 in the epidermis and sebaceous glands is downregulated. Following light irradiation, the skin exhibits a short‑term reduction in intercellular lipid synthesis within the stratum corneum, which diminishes intercellular adhesion in the cornified layer, disrupts the skin’s brick‑and‑mortar architecture, and temporarily impairs its moisturizing function, leading to erythema, dryness, and scaling in the short term. Concurrently, post‑PDT, the epidermis becomes thinner, while collagen and type I and III procollagens increase in the superficial dermis. Notably, the expression of TGF‑β and the type II TGF‑β receptor—both known to stimulate collagen synthesis—is markedly elevated, whereas the expression of MMP1, MMP3, and MMP12 decreases. These changes contribute to improvements in skin texture and appearance, thereby addressing photoaging. Ji et al. conducted a study on patients with photoaged skin and found that PDT can enhance the aesthetic appearance of photoaged skin, increase epidermal water content, and reduce transepidermal water loss (TEWL). Thus, PDT does not directly compromise the skin barrier; in the long term, it may even augment skin hydration and improve barrier function. Consequently, post‑treatment, enhanced moisturization and repair are recommended to prevent adverse effects associated with barrier disruption.

1.2 Photothermal Effect

The process by which biological tissues absorb laser energy and convert it into thermal energy is known as the photothermal effect. Since temperature governs the kinetic state of molecules, the biological effects of laser irradiation on tissues are determined by the temperature attained. For skin, a mild warming sensation is perceived when the temperature rises to 38–40°C; at 43–44°C, vasodilation and hyperemia occur, leading to erythema within seconds, followed by slight inflammatory exudate and mild edema after a few minutes—without causing irreversible damage. When skin temperature reaches 47–48°C, inflammatory exudate accumulates in the dermis within seconds, resulting in separation of the epidermis from the dermis and the formation of blisters. Further heating to 60–100°C can induce coagulative necrosis of epidermal cells within about 10 seconds; at temperatures exceeding 100°C, skin tissue undergoes boiling and evaporation, with steam‑induced pressure surges causing cellular and vascular disruption. If the temperature continues to rise, the skin begins to dehydrate and carbonize. Laser therapy for skin disorders predominantly exploits the photothermal effect, which, depending on the underlying mechanism, is classified into ablative and nonablative categories.

1.2.1 Ablative Laser

Ablative lasers can remove diseased or aged epidermal tissue and part of the dermis, while stimulating epidermal and dermal regeneration and remodeling to achieve therapeutic effects such as fading pigmentation, reducing wrinkles, and rejuvenating the skin. Ablative laser therapy is indicated for the ablation, perforation, or excision of various epidermal growths—such as tumors, nevi, and warts—as well as for resurfacing aged skin. During treatment, thermal injury also occurs, leading to denaturation of keratin in the stratum corneum and disruption of its normal architecture. Furthermore, it can induce protein denaturation, impair enzymatic reactions, and result in disturbances in the synthesis and metabolism of moisturizing factors and lipids, thereby compromising the skin’s “brick-and-mortar” structure. This weakens the skin’s barrier against external stimuli, making it more susceptible to environmental factors, ultraviolet radiation, and microbial invasion, which may lead to hyperpigmentation and increased infection risk. However, post‑treatment application of reparative moisturizing creams improves key indicators of skin barrier function—such as transepidermal water loss (TEWL), erythema, pigmentation, and surface capacitance—bringing these parameters close to levels observed after non‑ablative laser therapy.

1.2.2 Non-ablative laser

The theoretical foundation of non-ablative laser therapy was first articulated in 1983 by Anderson and Parrish in the journal Science, introducing the concept of selective photothermolysis (SP). According to this theory, based on the biological characteristics of target tissues, a laser of a specific wavelength can be selectively absorbed by the target tissue while being largely unaffected by surrounding tissues. When the laser pulse duration is shorter than or equal to the thermal relaxation time of the target tissue, and the energy density exceeds the threshold required to induce tissue damage, effective treatment of the affected area can be achieved. Simultaneously, because the heat generated by the laser energy does not have sufficient time to propagate into adjacent tissues, laser irradiation causes minimal injury to the surrounding normal tissue. This theory successfully reconciled efficacy with safety in laser therapy, marking a milestone in the history of laser medicine. Its formulation and ongoing refinement have revolutionized the treatment of various dermatological conditions, including port‑wine stains, vascular malformations, telangiectasias, as well as pigmented lesions and hirsutism. The underlying principle—leveraging the differential pigment concentrations between diseased and healthy tissues to select an appropriate laser wavelength, thereby maximizing absorption of laser energy in the target tissue and subsequently inducing localized temperature elevation and thermal injury to achieve specific therapeutic goals—has enabled laser therapy to move from a crude, non‑selective approach toward one that is precise and highly selective. Non‑ablative lasers are indicated for treating tattoos, vascular disorders, pigmented lesions, photoaging, and other skin conditions. Whether induced by ablative or non‑ablative lasers, skin injury triggers a local inflammatory response, initiating wound‑healing processes that lead to dermal collagen denaturation, fibroblast proliferation, enhanced collagen synthesis, increased skin hydration, smoother skin surface, and accelerated epidermal regeneration.

1.2.3 Fractional Laser

Nonablative lasers are effective for pigmentation and vascular conditions, but they fall short of ablative lasers in skin remodeling and scar treatment. In 2003, Anderson and Manstein proposed the theory of fractional photothermolysis (FP), suggesting that a specific class of lasers can create an array of microscopic thermal injury zones (microscopic treatment zones, MTZs) that penetrate to a defined depth without causing damage to surrounding tissues. When the area of thermal injury is sufficiently small and ample normal tissue remains nearby, the laser‑induced lesions heal rapidly with minimal scarring; the residual healthy tissue acts as a “bridge” during the repair process. This approach is why such lasers are also known as fractional lasers. The size of the MTZ varies with the density of the microarray. Because keratinocytes from adjacent normal tissue migrate quickly into the MTZ, even tiny wounds heal swiftly, minimizing direct disruption to the skin barrier. Laubach et al. systematically investigated the histopathological changes following treatment with the Fraxel nonablative fractional laser. Within one hour post‑treatment, the MTZ extended into the dermis, while the epidermal stratum corneum remained intact, with subepidermal clefts appearing and some vessels undergoing nonselective destruction. By seven days, the epidermis exhibited a remarkably healthy appearance, with normal or mildly thickened epidermal thickness, normal epidermal ridge morphology, and no evidence of dyskeratosis or other epidermal abnormalities. Hantash et al. examined the histopathological changes induced by ablative CO₂ fractional laser on human forearm skin. Immediately after treatment, both the epidermis and dermis in the ablated areas were covered by a thin layer of eschar. One month later, a normal stratum corneum had re‑formed. Following fractional laser therapy, the skin sustains thermal injury; within a short period, microscopic epidermal necrotic debris containing melanin—referred to as microepidermal necrotic debris (MEND)—appears in the basal layer clefts. The skin may develop bronze‑colored erythema, accompanied by edema, dryness, and scaling—signs of impaired skin barrier function. Typically, increasing the fractional spacing during the procedure, applying cold compresses postoperatively, and using growth factors or moisturizing reparative products can lead to symptom relief within about one week.

Fractional ablative laser can create microscopic, punctate lesions in the skin’s stratum corneum, thereby offering certain advantages in the field of transdermal drug delivery in dermatology. By inducing these micro‑punctate disruptions to the skin barrier, fractional ablative laser effectively enhances the therapeutic outcomes for cutaneous basal cell carcinoma, actinic keratosis, and hypertrophic scars, while also reducing the systemic concentrations of methotrexate used to treat psoriasis. Although non‑ablative fractional lasers do not directly produce such punctate lesions, they can modulate keratin expression via photothermal effects, thereby promoting transdermal penetration.

1.3 Optomechanical Effects

The mechanical effects induced by laser irradiation can be divided into two components: the pressure exerted on biological tissues by the laser’s radiation pressure—known as optical pressure, or primary pressure—and the pressures arising from thermal expansion and phase transitions in the tissue upon absorption of high‑intensity laser energy, as well as from ultrasound, shock waves, and electrostrictive phenomena—referred to as secondary pressure. Pressure changes in biological cells caused by lasers can alter cell and tissue morphology, generating internal or intercellular mechanical forces that profoundly influence cellular and tissue behavior. At present, the photomechanical effects of lasers have been successfully applied to the treatment of vascular and pigmented skin lesions. During the treatment of vascular lesions, the temperature of red blood cells rises at a rate of approximately 107°C per second, rapidly generating pressure waves that lead to vessel rupture and the formation of purpura. Concurrently, the mechanical forces generated within the cells during laser therapy compromise the integrity of keratinocytes, resulting in a cascade of clinical manifestations associated with impaired skin barrier function, such as erythema, exudation, and hyperpigmentation. Therefore, restoring the normal function of the skin barrier after laser treatment plays a decisive role in determining therapeutic outcomes.

[II] Photomodulation

Photomodulation, short for photobiomodulation, refers to the regulation of cellular activity using lasers, light-emitting diodes, or other light sources, via non‑photothermal mechanisms. The underlying mechanism of photomodulation is thought to involve the activation of an energy‑switching system at the mitochondrial level: absorbed light energy can enhance cellular functions, promote cell proliferation and migration, and modulate the levels of cytokines and inflammatory mediators. This process bears a striking resemblance to electron transport in chloroplasts during plant photosynthesis. Cytochromes are synthesized from protoporphyrin IX, and cytochrome molecules—particularly cytochrome c oxidase in the mitochondrial membrane—serve as chromophores that absorb light energy. Upon light absorption, “antenna” molecules in the mitochondrial membrane undergo conformational changes, driving the conversion of adenosine diphosphate (ADP) into adenosine triphosphate (ATP). This process supplies cells with additional energy for non‑mitotic cellular activities.

Light therapy acts on fibroblasts, keratinocytes, leukocytes, macrophages, and other cell types, playing a role in skin aging, wound healing, anti-inflammatory repair, acne, and other dermatological conditions. In a clinical trial conducted by Weiss et al., 90 patients received treatment with a 590 nm pulsed LED twice weekly for a total of eight weeks. The results showed that 90% of patients experienced improvement in photoaging symptoms, including enhanced skin texture, reduced periorbital wrinkles, and significant alleviation of skin erythema and pigmentation. Takezaki et al. used red LED light (Omnilux, 630 nm ± 3 nm) to irradiate the lateral lower extremity skin of six volunteers once weekly for eight consecutive weeks, at an intensity of 105 mW/cm² for 15 minutes each session, resulting in an energy density of 95 J/cm². After eight treatments, skin biopsies were obtained for both qualitative and quantitative PCR analysis. The findings revealed increases in both Th-1 and Th-2 lymphocyte numbers, with a more pronounced rise observed in Th-2 cells. Skin T cells play an important role in the body's immune defense system. Following the entry of bacteria or allergens into the dermis via the epidermis, these cells migrate from lymph nodes to local skin areas and actively contribute to wound healing.

In a clinical trial conducted by Alster et al., 20 patients underwent full‑face fractional 1,550‑nm non‑ablative laser resurfacing, followed immediately by 590‑nm LED irradiation of selected facial areas. The results showed that, at 24 hours, erythema in the LED‑treated regions was reduced compared with the control areas in all 20 patients; moreover, among the six patients who received higher‑energy‑density fractional laser treatment, erythema in the LED‑treated zones decreased further relative to the controls by 48 hours. These findings suggest that LED photomodulation can attenuate post‑fractional laser erythema and shorten its duration. In another clinical study evaluating intense pulsed light (IPL) for photoaging, 15 patients received immediate 590‑nm LED therapy on one side of the face following IPL treatment, with erythema and patient discomfort assessed at 24 hours. The results indicated that LED photomodulation not only facilitates the resolution of post‑IPL erythema but also alleviates post‑treatment discomfort.

[Three] Conclusion

When used to treat various skin conditions, laser therapy is a double-edged sword, often disrupting the skin’s barrier structure and function. Restoring the skin barrier is a complex process; selecting the appropriate laser platform, optimizing energy density, pulse width, and spot diameter, and understanding the endpoint responses of different lasers for specific skin disorders can help minimize barrier damage. In addition to standard post‑treatment measures such as ice application, moisturization, and sun protection, employing topical skin‑repair products and dressings or incorporating light‑modulation therapies can accelerate wound healing and enhance barrier recovery. Consequently, monitoring changes in and repair of the skin barrier during laser treatment provides critical guidance for clinicians seeking to mitigate adverse post‑laser reactions.

Note: This article is intended for academic exchange only and may not be used for commercial purposes. Copyright belongs to the original author; if any infringement occurs, please contact us immediately, and we will address it promptly.