Laser therapy has become one of the fastest-growing modalities for the management of aging skin, including the treatment of fine lines and deep wrinkles 1. Over the years, various wavelengths have been utilized, each with distinct advantages and disadvantages, tissue penetration depths, and energy distribution characteristics. While the lower third of the face has been a problematic area for many patients with respect to facial aging, clinicians have begun to treat deep nasolabial folds, marionette lines, and jowls not only using standard extra-oral protocols but also through innovative intra-oral applications. The aim of this clinical commentary was to describe for the first time the development of intra-oral lasering modalities using Neodymium-doped Yttrium Aluminum Garnet (Nd:YAG), Erbium-doped Yttrium Aluminum Garnet (Er:YAG), and carbon dioxide (CO2) lasers. Case examples are presented utilizing novel protocols described utilizing Nd:YAG, Er:YAG, and CO2 lasers. Exact protocols with their respective advantages and disadvantages are documented alongside before-and-after outcomes. Intra-oral lasering has emerged as a targeted protocol for the treatment of deep nasolabial folds and marionette lines. Given that the lower third of the face is often a challenging area to treat, clinicians hypothesized that combining extra-oral and intra-oral laser application could deliver more energy to these relatively thin tissue regions. Interestingly, several studies have already highlighted that lasers can induce soft palate tightening to increase airway space in individuals who are prone to snoring or obstructive sleep apnea 2-5. These therapies leverage the photothermal capabilities of Neodymium-doped Yttrium Aluminum Garnet (Nd:YAG) and Erbium-doped Yttrium Aluminum Garnet (Er:YAG) lasers to stimulate new collagen formation in the soft palate and other mucosal tissues 2-4. The Nd:YAG laser is a deep penetrating, non-ablative laser capable of photobiomodulation, stimulating tissue regeneration across multiple layers 6-9. Interestingly, a non-contact Er:YAG laser modality (Smoothmode) was proposed to deliver heat energy sufficient to tighten tissues without ablation 10. These non-ablative therapies have long been utilized successfully for female urinary incontinence, demonstrating their safety and efficacy on other mucosal tissues 11-14. Building on these applications, the concept of intra-oral non-ablative therapy was adapted for soft tissues in the lower face to enhance nasolabial folds and marionette lines 15-20. The Smoothmode technology consists of a series of sub-ablative micro pulses of Er:YAG laser energy 10. These brief temperature pulses at the mucosal surface are transformed via heat diffusion into a prolonged thermal pulse within deeper connective tissue layers 2. This induces two complementary regenerative processes: 1 an indirect triggering effect by short-duration heat shock of the mucosal tissue; and 2 a direct, slow thermal effect on the connective tissues 2. Both processes stimulate collagen remodeling and neocollagenesis. Histological assessment in an animal model of the soft palate showed mucosal shrinkage without bleeding, severe inflammation, carbonization, or necrosis 21. In addition, a pilot clinical study by Lee et al. 16 showed that the photothermal effects of intra-oral Er:YAG lasering significantly increased the airway space/volume and minimal cross-sectional area at 12 weeks post-laser treatment, as measured by three-dimensional Cone Beam Computed Tomography (CBCT). Given their minimal invasiveness, non-ablative intra-oral therapies represent an ideal complement to extra-oral laser therapy, as the two approaches do not interfere with one another. The Smoothlase protocol combines Nd:YAG and Er:YAG lasers to improve skin elasticity, tone, and texture in a minimally invasive manner. Initially, the Nd:YAG laser is applied to pre-heat tissues to approximately 40°C in distinct patterns, followed by the Er:YAG laser delivered in a proprietary “Smoothmode” pulse sequence (Fotona). Smoothmode delivers a rapid burst of pulses over a short period, creating deep tissue heating, immediate collagen contraction, and progressive tissue tightening 22, 23. Fractional non-ablative carbon dioxide (CO2) lasers also represent a significant advancement in mucosal tissue therapy, offering effective remodeling with minimal downtime 24, 25. Using a fractional delivery system, these lasers create microthermal treatment zones (MTZs) 26, 27, that leave surrounding tissue intact while inducing controlled thermal injury in deeper mucosal layers. Similar to Smoothmode Er:YAG technology, their therapeutic effect relies on promoting collagen synthesis, elastin remodeling, and overall tissue regeneration through heat-induced cellular stress 28-30. Unlike traditional ablative CO2 lasers, which remove both superficial and deeper tissue layers, fractional CO2 lasers preserve much of the surface epithelium, allowing for faster recovery while maintaining strong clinical efficacy 31, 32. At the cellular level, the benefits of fractional CO2 lasers are mediated by the activation of heat shock proteins (HSPs) and pro-inflammatory cytokines 33-35. Thermal exposure triggers the upregulation of HSP25, HSP47, HSP70, HSP72, and HSP90, which protect cells from further thermal damage, facilitate protein repair, and support survival 33-35. The response enhances extracellular matrix (ECM) remodeling, specifically collagen type I and III synthesis, which are critical for structural integrity 36, 37. Furthermore, laser-induced thermal stress stimulates cytokines, such as interleukin-1 (IL-1) 38 and transforming growth factor-beta (TGF-β) 38, promoting angiogenesis, fibroblast activation, and collagen deposition, all of which accelerate mucosal tissue regeneration 39-42. Fractional non-ablative and ablative CO2 lasers differ in depth and mechanism of action. Ablative systems vaporize epithelial and lamina propria tissues, producing deeper micro-ablative zones, more extensive tissue removal, and pronounced resurfacing 31, 43-47. Non-ablative systems instead generate controlled thermal injury without extensive epithelial loss, sparing the tissue framework and reducing downtime and complications. Both stimulate wound healing and collagen synthesis, but the non-ablative approach typically balances efficacy with safety, making it especially suited for mucosal applications where barrier preservation is critical. From a wavelength perspective, the CO2 laser (10 600 nm) offers distinct advantages over the Er:YAG lasers (2940 nm). Both target water, the principal component of mucosa, but the CO2 lasers disperse heat more deeply, achieving effective coagulation and collagen stimulation in both superficial and deeper layers. In contrast, Er:YAG energy is more strongly absorbed at the surface, limiting penetration and confining its effect to remodeling 48-50. While Er:YAG lasers excel at precise ablation and superficial resurfacing, CO2 lasers are preferred when deeper structural remodeling is required, such as in mucosal rejuvenation that affects nasolabial folds and marionette lines. In summary, fractional CO2 lasers enhance mucosal regeneration through HSP-mediated cytoprotection and cytokine-regulated healing pathways. Furthermore, their deeper tissue penetration compared with Er:YAG lasers enables robust collagen and elastin remodeling across multiple tissue layers, making them a versatile and effective tool for both esthetic and functional mucosal treatments. Both demo patients signed an informed written patient consent as per journal guidelines. The authors declare that the investigations were carried out following the rules of the Declaration of Helsinki of 1975, which was revised in 2013. An IRB was not needed for this study due to the retrospective nature of this study (Sterling IRB). Clinical protocols for intra-oral laser applications—whether using Nd:YAG, Er:YAG, or CO2 lasers—generally follow similar treatment patterns. A typical procedure initiates with a series of passes delivered along three intraoral vectors (Figure 1A). The clinician begins treatment at the designated starting point (Point 1) and proceeds sequentially to the end point (Point 6), with adjustments made according to patient anatomy. To minimize the risk of thermal accumulation, a maximum of 15% overlap between adjacent tissue points is recommended. While three treatment vectors represent the standard approach, additional passes may be incorporated depending on the clinical severity. Following completion of these intraoral passes, attention is directed toward the nasolabial folds and marionette lines (Figure 1B). Standard treatment typically requires two zones for the nasolabial fold and one for the marionette line, using a 7 mm spot size. Since this area is more sensitive than the intraoral mucosa, laser energy is usually reduced by around 25%. Treatment is usually sequenced beginning with the lower portion of the nasolabial fold, followed by the marionette line, and concluding with the upper portion of the fold. This sequence allows for adequate thermal relaxation of the nasolabial fold and prevents overheating, especially relevant in patients with smaller intraoral regions. Finally, the mucosal surfaces corresponding to perioral rhytides, commonly known as smoker's lines, are addressed according to manufacturer-specific protocols (Figure 1C). Both lower and upper regions are treated; nonetheless, direct application to the lips is avoided owing to heightened sensitivity and the potential for unintended lip plumping. A novel protocol involves the sequential use of Nd:YAG and Er:YAG lasers, as illustrated in Figure 2A and demonstrated in video (QR Code 1) on a 31-year-old healthy ASA I female patient following informed consent. During the initial stage, the R30 handpiece is utilized with the Nd:YAG laser (1064 nm; Fotona Lightwalker, Figure 4A). Energy delivery usually consists of around 300 J/in.2 directed into the mucosal tissue, resulting in a total of 600 J applied per cheek. An additional 300 J may be applied intraorally around the perioral area to enhance coverage. Table 1 demonstrates the standard operating parameters, while Figure 2B illustrates the recommended handpiece positioning and aiming beam distance utilized during this protocol. Laser parameters are set to Smoothmode with a fluence of 6–8 J/cm2 at 1.5–2.0 Hz, delivering six Smoothmode pulses per spot over four treatment passes (Table 2). This stage is applied systematically to three main regions: 1 the cheeks Figure 2D 2; nasolabial folds and marionette lines Figure 2E; and 3 the perioral regions (Figure 2F). A step-by-step protocol is presented in QR code 1. The second protocol investigated by the authors employs the CO2 laser, with a corresponding video presented in QR Code 2 on a healthy 41-year-old ASA I male patient. A straight-firing handpiece is utilized for treatment of the cheek and perioral areas, while a side-firing handpiece is used for the nasolabial folds and marionette lines (Deka; Figure 3A). Typical parameters include 4–6 W power with a dwell time of 1200 μs and spacing of 500 μm (Table 3). These handpieces are systematically applied to the cheeks (Figure 3B), nasolabial folds/marionette lines (Figure 3C), and perioral region (Figure 3D). A step-by-step protocol is presented in QR code 2. Figure 4B demonstrates a before and after clinical case incorporating these therapies. While this article highlights recent advancements in intraoral laser therapy in facial esthetics, it is noteworthy to highlight that these case reports provide only preliminary observations and do not constitute scientific validation. There is a lack of well-designed clinical studies investigating the use of intra-oral lasering with no randomized clinical studies to date evaluating patient-reported outcomes and/or clinical photos/scans. Therefore, well-conducted randomized clinical studies are needed to evaluate the effectiveness of intraoral lasering when compared to conventional extraoral fractional lasers, fillers, or surgical lifting procedures. Notably, while both protocols available to date utilizing intra-oral lasering focus on the non-ablative nature of the developed protocol, no study to date has assessed the safety and efficacy with proper clinical data over a large patient population. Therefore, additional well-designed studies with long-term follow-up are needed with proper documentation, validation, and standardization. Furthermore, no study to date has evaluated potential adverse events, inclusion/exclusion criteria for treatment, or potential contraindications of such intra-oral lasering. A structured comparison of outcomes, safety profiles, and long-term efficacy across different wavelengths would be valuable and should be studied in future RCTs. Furthermore, it would be rationale to have differences in depth of penetration of the lasers extra-orally versus intra-orally along with histological evaluation as to which facial layers are optimally being targeted. This article highlights recent advancements in intraoral laser therapy for facial esthetics. Although further research is needed to evaluate the effectiveness of individual protocols and combination approaches, current evidence suggests that intraoral energy delivery is both safe and well-tolerated, particularly when integrated with complementary therapies. Once regarded as an approach associated with high morbidity and prolonged downtime, laser therapy has evolved substantially, with contemporary systems providing favorable outcomes and minimal recovery periods. Looking ahead, comparative randomized clinical studies will be essential to establish optimized guidelines and standardized protocols for intraoral applications. Collectively, these advancements point toward a new era of biologically driven, minimally invasive esthetic therapies. Conceptualization, R.J.M., E.M., A.D.G.P., P.A.; Methodology, R.J.M., E.M., and P.A.; formal analysis, R.J.M., and A.D.M.; investigation, R.J.M., E.M.; resources, R.J.M., E.M., A.D.G.P., P.A.; writing – original draft preparation, R.J.M., E.M., and P.A.; writing – review and editing, R.J.M., E.M., A.D.G.P., P.A.; supervision, A.D.G.P. and P.A.; project administration, R.J.M., E.M., A.D.G.P., P.A. All authors have read and agreed to the published version of the manuscript. The authors would like to thank Vivid Alchemy (Nadem Hamad and Dalia Hamad) for providing the photos and videos utilized in this article. The authors would also like to thank Dr. Scott Parker for providing valuable insights on laser therapy applications in esthetic medicine. No form of AI was used in this manuscript. Open access publishing facilitated by Universitat Bern, as part of the Wiley - Universitat Bern agreement via the Consortium Of Swiss Academic Libraries. The authors have nothing to report. The authors have nothing to report. Informed consent was provided prior to blood draw to conduct the outlined experiments. Photo patient consents were received from all patients according to Wiley standards. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Richard J. Miron
Elsa McGilvray
Ana De Gomez Paz
Journal of Cosmetic Dermatology
University of Bern
Jupiter Medical Center
SGS (Portugal)
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Miron et al. (Fri,) studied this question.
www.synapsesocial.com/papers/69fd7e79bfa21ec5bbf06b68 — DOI: https://doi.org/10.1111/jocd.70890