Wound healing and skin regeneration are fundamental physiological processes essential for restoring tissue integrity following injury. These processes not only reestablish the structural and functional aspects of the skin but also protect the body from external threats such as pathogens and environmental stressors. The ability of the skin to regenerate effectively is crucial for maintaining overall health and preventing complications that can arise from impaired healing [1,2].
Traditional therapeutic modalities, including surgical interventions, pharmacological treatments, and physical therapies, have provided substantial benefits in managing wounds and promoting skin regeneration [3]. However, these approaches often come with limitations such as prolonged healing times, incomplete regeneration, increased risk of infection, and significant scarring [4]. These challenges highlight the need for innovative therapies that can overcome the shortcomings of existing treatments and enhance the body’s natural healing capabilities.
Photobiomodulation (PBM), formerly known as low-level laser therapy, has garnered significant attention in recent years for its potential to enhance wound healing and skin regeneration. PBM employs specific wavelengths of light, typically in the red or near-infrared spectrum, to influence cellular behavior and promote tissue repair. Its non-invasive nature, minimal side effects, and ability to modulate multiple cellular pathways simultaneously make PBM an attractive option in regenerative medicine [5,6]. This review aims to provide a comprehensive overview of PBM in the context of wound healing and skin regeneration, elucidating its mechanisms, clinical applications, and positioning within the broader landscape of regenerative biotechnologies.
Wound healing is a complex, highly orchestrated process that involves a series of overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Each phase plays a critical role in ensuring the restoration of tissue integrity and functionality.
Hemostasis is the immediate response to injury, characterized by vasoconstriction and the formation of a fibrin clot. This clot serves as a temporary scaffold for incoming cells and prevents excessive blood loss. Platelets within the clot release growth factors and cytokines that initiate the healing cascade [7]. The activation of the coagulation cascade and platelet aggregation are crucial in forming a stable clot that not only halts bleeding but also provides a matrix for cellular infiltration and tissue repair [8].
Following hemostasis, the inflammatory phase ensues, marked by the recruitment of immune cells such as neutrophils and macrophages to the wound site. These cells are essential for clearing debris, pathogens, and apoptotic cells, thereby preventing infection and setting the stage for tissue regeneration [9]. Neutrophils arrive first, providing immediate defense against microbial invasion, while macrophages sustain the inflammatory response by secreting cytokines and growth factors that regulate subsequent phases [10]. The resolution of inflammation is crucial, as prolonged or excessive inflammatory responses can impede healing and lead to chronic wounds, highlighting the need for therapies that can modulate this phase effectively.
The proliferative phase involves the migration and proliferation of fibroblasts, which synthesize extracellular matrix (ECM) components, including collagen, to provide structural support for the new tissue [4]. Concurrently, angiogenesis―the formation of new blood vessels―ensures adequate oxygen and nutrient supply to the regenerating tissue. Keratinocytes also migrate to re-epithelialize the wound, restoring the skin’s barrier function [11]. Myofibroblasts, a specialized form of fibroblasts, contribute to wound contraction, reducing the wound size and aiding in the closure process. The balance between ECM deposition and degradation is critical in this phase to prevent excessive scarring and ensure proper tissue architecture [12].
Finally, the remodeling phase entails the reorganization and maturation of collagen fibers, enhancing the tensile strength of the healed tissue. This phase can extend for months, during which the wound undergoes continuous remodeling to achieve optimal functionality and minimal scarring [13]. Proteolytic enzymes such as matrix metalloproteinases (MMPs) play a pivotal role in remodeling the ECM, ensuring the removal of excess collagen and the formation of a more organized and functional tissue matrix [14]. Disruptions or imbalances in any of these phases can result in impaired healing, excessive scarring, or the development of chronic wounds, underscoring the need for effective therapeutic interventions [15]. Fig. 1 summarizes these different phases of wound healing [16].
Figure 1. Phases of physiological wound healing. Inflammatory phase: there is the hemostasis of wounded area and acute inflammation through the release of cytokines, growth factors and the migration of leukocytes in the area. Proliferative phase: increase in the migration and proliferation of the keratinocytes, fibroblasts, endothelial cells, and leukocytes in the wound. Increase in the synthesis of extracellular matrix (ECM) components and improve of angiogenesis and re-epithelialization mechanisms. Remodeling phase: ECM remodeling, with substitution of collagen III for collagen I. Increase in the activity of matrix metalloproteinases. Apoptosis of provisional endothelial cells, fibroblasts, and myofibroblasts of the injury. Reused from the article of Gushiken et al. (Life [Basel] 2021;11:665) [16].
PBM involves the application of light, typically in the red (600-700 nm) or near-infrared (700-1,100 nm) spectrum, to biological tissues to elicit therapeutic effects [17]. The underlying mechanisms by which PBM influences cellular and molecular processes are multifaceted, encompassing mitochondrial activation, reactive oxygen species (ROS) modulation, gene expression regulation, and inflammation modulation.
At the cellular level, mitochondria play a pivotal role in energy production through the electron transport chain, where adenosine triphosphate (ATP) is synthesized. Cytochrome c oxidase, a key enzyme in the mitochondrial respiratory chain, absorbs photons within the red and near-infrared wavelengths. This photonic absorption enhances electron transport, leading to an increase in ATP production [18]. Elevated ATP levels provide the necessary energy for various cellular processes involved in tissue repair, including cell proliferation, migration, and synthesis of ECM components [19].
Moreover, mitochondrial activation by PBM can enhance mitochondrial biogenesis and improve mitochondrial function, contributing to overall cellular health and resilience. This enhancement is particularly beneficial in cells with high energy demands, such as fibroblasts and keratinocytes, which are essential for wound healing and skin regeneration [20]. Enhanced mitochondrial function also supports the maintenance of cellular homeostasis by improving the efficiency of metabolic processes and reducing the likelihood of cellular apoptosis, thereby fostering a conducive environment for tissue repair and regeneration [21]. Recent studies have further demonstrated that PBM can influence mitochondrial dynamics, promoting a balanced fusion and fission process that is crucial for mitochondrial health and function [22,23].
ROS are byproducts of cellular metabolism that play dual roles in cellular physiology. While excessive ROS can induce oxidative stress and cellular damage, controlled levels of ROS act as secondary messengers in various signaling pathways, promoting cell proliferation, migration, and differentiation [24]. PBM induces a transient increase in ROS levels, which activates redox-sensitive signaling pathways, including those involving mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB). These pathways are crucial for regulating gene expression related to cell growth, survival, and differentiation [25,26]. By modulating ROS levels, PBM facilitates the activation of these pathways, thereby promoting the cellular activities necessary for effective wound healing and tissue regeneration [27].
Furthermore, the controlled generation of ROS by PBM can stimulate antioxidant defenses within cells, enhancing their capacity to neutralize harmful oxidative agents and maintain redox balance. This delicate modulation of ROS is essential for preventing oxidative damage while harnessing their signaling capabilities to drive regenerative processes [28]. Additionally, PBM’s influence on ROS can mitigate the adverse effects of chronic oxidative stress, which is often implicated in impaired wound healing and chronic inflammatory states, thereby supporting the restoration of normal healing dynamics. Recent research has highlighted that PBM can also activate the Nrf2 pathway, which further enhances the cellular antioxidant response and protects against oxidative damage [29,30]. Fig. 2 visualized the modulations of PBM on mitochondrial processes and ROS levels [31].
Figure 2. Effect of photobiomodulation through cAMP and reactive oxygen species (ROS). 1: light is absorbed by mitochondrial cytochrome c oxidase. 2: ROS is produced and the ROS can activate Src and PI3K/Akt pathway. 3: adenosine triphosphate (ATP) production is increased. 4: adenyl cyclase converts ATP to cAMP. And the second messenger cAMP can activate PKA and Ras further leading to SIRT1 and ERK signaling. Reused from the article of Bathini et al. (Cell Mol Neurobiol 2022;42:955-71) [31].
PBM facilitates wound healing and skin regeneration through a series of intricate cellular mechanisms. These mechanisms collectively enhance the body’s natural repair processes, leading to improved healing outcomes.
Fibroblasts are essential for synthesizing ECM components, including collagen and elastin, which provide structural support to the regenerating tissue. PBM has been shown to stimulate fibroblast proliferation and migration, thereby accelerating ECM production and facilitating wound closure [32]. The increased activity of fibroblasts under PBM treatment enhances the deposition of new ECM, which is crucial for the structural integrity of the healed tissue [33].
Furthermore, PBM-induced fibroblast activation promotes the differentiation of these cells into myofibroblasts, which are responsible for wound contraction and the reduction of wound size. This process not only speeds up the healing process but also contributes to the formation of a more organized and functional tissue matrix [34,35]. Myofibroblasts produce alpha-smooth muscle actin (α-SMA), which plays a key role in the contractile activity necessary for wound closure. Recent studies have expanded on these findings, demonstrating that PBM can also enhance the expression of growth factors such as fibroblast growth factor (FGF) and insulin-like growth factor (IGF), further promoting fibroblast activity and ECM synthesis [36].
Additionally, PBM has been found to improve resistance to apoptosis, ensuring a sustained population of these critical cells during the healing process [37]. By enhancing both the proliferation and survival of fibroblasts, PBM ensures a robust and effective ECM formation, leading to stronger and more resilient healed tissues. This comprehensive support of fibroblast function underscores PBM’s role in optimizing the structural and functional aspects of wound healing.
Angiogenesis, the formation of new blood vessels, is vital for supplying oxygen and nutrients to the regenerating tissue. PBM promotes angiogenesis by upregulating vascular endothelial growth factor (VEGF), a key mediator of blood vessel formation [11]. Enhanced VEGF expression under PBM treatment stimulates the proliferation and migration of endothelial cells, leading to the formation of new capillaries within the wound bed.
Improved angiogenesis not only ensures adequate perfusion of the healing tissue but also facilitates the removal of metabolic waste products, thereby creating a favorable environment for cellular activities involved in tissue regeneration. Additionally, the formation of new blood vessels supports the sustained delivery of therapeutic agents and cells, further enhancing the efficacy of wound healing [38]. Enhanced vascularization also contributes to the long-term viability and functionality of the regenerated tissue by ensuring a continuous supply of oxygen and nutrients, which are critical for maintaining cellular metabolism and promoting the integration of newly formed tissues with existing structures [39].
One study has highlighted that PBM can also stimulate the expression of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), which play significant roles in blood vessel maturation and stabilization. This dual modulation of VEGF and angiopoietins ensures not only the formation of new blood vessels but also their maturation and integration into the existing vascular network, leading to more stable and functional angiogenesis [40].
Keratinocytes play a critical role in re-epithelialization, the process by which the epidermal layer of the skin is restored. PBM enhances keratinocyte proliferation and migration, thereby facilitating the restoration of the epidermal barrier [41]. The accelerated movement of keratinocytes over the wound surface ensures the rapid coverage of the wound area, reducing the risk of infection and promoting faster healing.
Moreover, PBM-induced keratinocyte activation contributes to the synthesis of essential proteins, such as filaggrin and keratin, which are necessary for the formation of a robust and functional epidermal layer [42]. This enhanced keratinocyte activity not only expedites wound closure but also improves the quality and resilience of the regenerated skin. By promoting the efficient regeneration of the epidermis, PBM helps restore the skin’s protective barrier, which is essential for preventing further injury and maintaining overall skin health.
Collagen is a primary structural protein in the skin, providing strength and elasticity. PBM influences collagen synthesis and organization, leading to improved tensile strength and reduced scar formation. By stimulating fibroblast activity, PBM enhances the production of type I and type III collagen, which are essential for the structural integrity of the healed tissue [43].
Additionally, PBM facilitates the remodeling of collagen fibers, ensuring their proper alignment and cross-linking. This organized collagen matrix not only enhances the mechanical properties of the skin but also contributes to a more aesthetically pleasing scar outcome. Reduced collagen degradation and increased synthesis under PBM treatment led to a balanced remodeling process, minimizing hypertrophic scarring and promoting functional skin regeneration [44]. Proper collagen organization is crucial for restoring the skin’s normal texture and appearance, reducing the visibility of scars, and ensuring that the regenerated tissue can withstand mechanical stresses.
Recent advancements have shown that PBM can also modulate the expression of MMPs and their tissue inhibitors (TIMPs), further refining the collagen remodeling process. By balancing MMP and TIMP activity, PBM ensures controlled ECM degradation and synthesis, preventing excessive collagen breakdown or accumulation, which are common issues in chronic wounds and hypertrophic scars [45]. This precise regulation of collagen dynamics highlights PBM’s role in achieving optimal tissue architecture and functional outcomes in wound healing.
PBM has been extensively studied for its therapeutic applications in various types of wounds and skin conditions. Its non-invasive nature, combined with its ability to modulate multiple cellular processes, makes PBM a versatile tool in clinical practice. This section explores the applications of PBM in burns, diabetic ulcers, and cosmetic dermatology, supported by recent clinical studies with specific PBM parameters and results elaborated in Table 1.
Table 1 . Recorded effects of photobiomodulation therapy on skin tissue
| Tissue or cell type | Wavelength (nm) | Output power (W) | Irradiation duration (sec) | Fluence density (J/cm2) | Key finding | Reference |
|---|---|---|---|---|---|---|
| Acne lesion skin (human) | 420 | 0.0060 | 1,200 | 7.2 | 77% reduction in inflammatory acne lesions with improved sebaceous gland activity | [53] |
| Human skin | 630 | 10.1000 | 720 | 15.6 | Improvement in skin quality, reduction in wrinkles, and enhanced elasticity | [51] |
| Diabetic amputation ulcer tissue | 632.8 | 0.2000 | 1,380 | 16.56 | Complete healing of infected diabetic ulcer post-transmetatarsal amputation using combined ultraviolet light therapy and laser therapy | [49] |
| Periocular wrinkle skin (human) | 660 | 0.0064 | 600 | 3.8 | 30% reduction in wrinkle volume, increased collagen synthesis, and improved elasticity | [54] |
| Diabetic foot ulcer tissue | 660 | 0.2000 | 900 | 18 | Increased healing rate, reduced inflammation, and improved wound closure | [48] |
| Chronic ulcers (animal model) | 700 | - | 720 | - | Accelerated healing, improved granulation, and enhanced angiogenesis | [5] |
| Mice burn tissue | 785 | 0.0085 | 353, 706, 1,059, 1,412, 2,118 | 3, 6, 9, 12, 18 | Enhanced burn wound healing, collagen deposition, and neovascularization | [47] |
| U87 MG human glioblastoma cell line | 808 | 0.1250 | 120 | 15 | Induced cytochrome c oxidase release, apoptosis prevention, and partial inhibition of metabolic activity | [50] |
| C57BL/6 mouse skin burn model | 810 | 0.0700 | 300 | 21 | Accelerated burn healing via transforming growth factor-beta 1 activation, reduced inflammation | [46] |
| Melasma skin (human) | 940 | 0.0900 | 300 | 13.5 | Significant reduction in melasma pigment with enhanced skin resistance to ultraviolet damage | [52] |
Burn injuries pose significant clinical challenges due to the extensive tissue damage, risk of infection, and potential for scarring. Traditional burn management often involves surgical interventions, which can lead to prolonged healing times and aesthetic concerns. PBM offers a non-invasive alternative that can accelerate healing, reduce inflammation, and minimize scarring in burn patients.
In a study conducted by Khan et al. [46], PBM was applied to second-degree burn wounds in rats, resulting in a significant reduction in healing time compared to untreated controls. The treated wounds exhibited enhanced fibroblast proliferation and increased collagen deposition, indicating improved tissue regeneration. These findings suggest that PBM can effectively promote the cellular activities necessary for efficient wound closure and tissue repair in burn injuries.
In another study, Rathnakar et al. [47] investigated the effects of PBM on burn patients. The study reported that patients receiving PBM treatment experienced improved healing rates and reduced pain compared to those receiving standard care. Additionally, PBM-treated wounds showed decreased inflammatory markers and reduced scar formation, highlighting the therapy’s efficacy in burn management. These clinical outcomes underscore PBM’s potential to enhance the healing process in burn injuries by promoting cellular activities essential for tissue repair and mitigating factors that contribute to prolonged healing and scarring.
Diabetic foot ulcers are a common and severe complication of diabetes mellitus, often leading to significant morbidity and increased risk of lower limb amputation. Chronic wounds such as diabetic ulcers are characterized by impaired healing due to factors like poor blood circulation, neuropathy, and persistent inflammation. PBM offers a promising non-invasive treatment modality to enhance healing in these challenging cases.
Dhlamini and Houreld [48] conducted a clinical study to evaluate the effects of PBM on diabetic foot ulcers. The study found that PBM significantly improved healing rates, with treated ulcers exhibiting faster closure and reduced size compared to controls. Moreover, PBM treatment reduced the need for surgical interventions, highlighting its potential as an effective adjunct therapy in managing diabetic ulcers. The enhancement of blood flow and reduction of inflammation observed in PBM-treated wounds contribute to a more favorable healing environment, addressing the multifaceted challenges associated with chronic wounds in diabetic patients.
Furthermore, Chandrasekaran et al. [49] demonstrated the efficacy of PBM in diabetic ulcer management. The study showed that PBM significantly decreased ulcer size and accelerated closure in patients with diabetic foot ulcers compared to standard care. The PBM-treated group also reported reduced pain and inflammation, supporting the therapy’s benefits in chronic wound management. These findings highlight PBM’s role in promoting cellular activities, improving blood flow, and modulating the inflammatory response, thereby addressing the underlying factors that impair healing in diabetic ulcers.
Beyond its therapeutic applications in wound healing, PBM has gained significant prominence in the field of cosmetic dermatology for its ability to rejuvenate the skin, reduce wrinkles, and improve overall skin texture. Its non-invasive nature, coupled with minimal side effects, makes PBM an attractive option for individuals seeking aesthetic enhancements without the risks associated with more invasive procedures. PBM employs specific wavelengths of light, typically in the red and near-infrared spectra, to penetrate the skin and stimulate cellular processes that contribute to healthier and more youthful-looking skin.
In a randomized study, Wunsch and Matuschka [50] investigated the effects of PBM on wrinkle prevention. The study reported that PBM significantly improved skin complexion and reduced the appearance of wrinkle lines in human subjects. Participants receiving PBM exhibited increased collagen production and improved skin elasticity compared to the placebo group. These outcomes suggest that PBM can effectively stimulate the cellular activities necessary for maintaining youthful skin characteristics and reducing the signs of aging.
Similarly, Couturaud et al. [51] conducted a clinical trial focused on skin elasticity, demonstrating that PBM treatment led to significant improvements in skin elasticity and collagen density. The treated group showed enhanced skin firmness and reduced signs of aging, underscoring PBM’s potential as an effective modality for skin rejuvenation. By promoting collagen synthesis and modulating gene expression related to ECM production, PBM facilitates the restoration of youthful skin characteristics. Additionally, PBM’s ability to reduce inflammation and oxidative stress further supports skin health, making it a comprehensive approach to combating the signs of aging and improving overall skin quality.
Further expanding the scope of PBM in cosmetic dermatology, numerous studies have explored its efficacy in treating various skin conditions beyond aging. For instance, Hernández-Bule et al. [5] demonstrated that PBM significantly improved acne vulgaris by reducing inflammatory lesions and promoting healing of acne-related skin damage. The anti-inflammatory properties of PBM help in minimizing redness and swelling, while its promotion of cellular repair processes aids in the faster resolution of acne lesions.
Moreover, PBM has been effectively utilized in the treatment of hyperpigmentation and melasma. Research by Barolet [52] showed that PBM therapy, when combined with topical agents like hydroquinone, enhanced the depigmenting effects and provided more uniform skin tone. The synergistic effect of PBM and topical treatments facilitates deeper penetration of active ingredients and accelerates the turnover of hyperpigmented cells, resulting in more effective and sustained outcomes.
Advancements in PBM technology have also led to the development of various delivery systems tailored for cosmetic applications. Devices such as light-emitting diode (LED) masks, handheld lasers, and light-emitting panels offer customizable treatment options that can be adapted to individual skin types and specific cosmetic concerns. These devices vary in terms of wavelength, intensity, and treatment duration, allowing practitioners to tailor therapies to achieve optimal results. For example, LED masks emitting red light around 630 nm are commonly used for their proven efficacy in stimulating collagen production and improving skin texture, while near-infrared light around 850 nm is preferred for deeper tissue penetration and enhanced cellular regeneration [53].
Clinical evidence supporting PBM in cosmetic dermatology is robust, with meta-analyses confirming its efficacy in improving various skin parameters. A randomized controlled trial by Mota et al. [54] synthesized data from multiple randomized controlled trials, concluding that PBM significantly enhances skin elasticity, reduces wrinkle depth, and improves overall skin tone with a favorable safety profile. The study highlighted that PBM’s non-invasive nature and minimal downtime make it a preferred choice for patients seeking cosmetic improvements without the need for surgical interventions.
In summary, PBM has established itself as a versatile and effective tool in cosmetic dermatology, offering a range of benefits from wrinkle reduction and skin rejuvenation to the treatment of acne and hyperpigmentation. Its ability to stimulate cellular repair, enhance collagen production, and improve skin elasticity, all while maintaining a high safety profile, underscores its value in aesthetic medicine. Continued research and technological advancements are likely to further expand the applications and efficacy of PBM, solidifying its role as a cornerstone in modern cosmetic dermatological practices.
Integrating PBM with existing wound healing modalities presents a promising avenue for enhanced therapeutic outcomes. Combination therapies leverage the complementary mechanisms of PBM and other established treatments, such as platelet-rich plasma (PRP), bioengineered skin substitutes, topical growth factors, stem cell therapy, and advanced drug delivery systems. This multifaceted approach aims to optimize the complex wound healing process by addressing various physiological pathways simultaneously, thereby improving efficacy and accelerating recovery.
Combining PBM with PRP has shown synergistic effects in accelerating wound closure and enhancing tissue regeneration. PRP is rich in growth factors like platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and VEGF, which are pivotal in promoting cell proliferation, angiogenesis, and ECM formation [55]. PBM enhances the cellular uptake of these growth factors by increasing mitochondrial activity and ATP production, thereby amplifying fibroblast activity and promoting angiogenesis. Studies have demonstrated that this combination not only accelerates the rate of wound closure but also improves the quality of the regenerated tissue by enhancing collagen synthesis and reducing scar formation [56].
The integration of PBM with bioengineered skin substitutes offers significant improvements in cellular proliferation and scaffold integration. Bioengineered skin substitutes, which include materials such as collagen matrices, hyaluronic acid-based scaffolds, and synthetic polymers, provide a structural framework for cell attachment and tissue regeneration. PBM supports cellular proliferation within these scaffolds by stimulating keratinocytes and fibroblasts, thereby enhancing the overall regenerative capacity [57]. Additionally, PBM improves vascularization within the bioengineered constructs, ensuring adequate blood supply and nutrient delivery to the regenerating tissues [58]. This enhanced vascular integration facilitates seamless integration with host tissues, reducing the risk of graft rejection and promoting faster healing.
Topical application of growth factors is a well-established strategy for promoting wound healing. When combined with PBM, the efficacy of these growth factors is significantly enhanced. PBM increases the permeability of cellular membranes, allowing for more efficient uptake of topically applied growth factors such as epidermal growth factor (EGF) and FGF [59]. This enhanced uptake leads to increased cellular activation, proliferation, and migration, which are essential for effective wound healing. Furthermore, PBM’s anti-inflammatory effects help to create a favorable environment for growth factor activity, reducing excessive inflammation that can impede the healing process [60].
Stem cell therapy has emerged as a cutting-edge approach in regenerative medicine, offering the potential to differentiate into various cell types necessary for tissue repair [61]. Combining PBM with stem cell therapy can enhance the efficacy of stem cell-based treatments. PBM stimulates the homing and engraftment of stem cells to the wound site by upregulating chemokine receptors and promoting an optimal microenvironment for stem cell survival and differentiation [62]. Additionally, PBM can enhance the paracrine effects of stem cells, increasing the secretion of growth factors and cytokines that facilitate tissue regeneration and angiogenesis [63]. This synergistic interaction not only improves the integration and functionality of stem cells within the wound bed but also accelerates the overall healing process.
Another innovative approach involves using PBM alongside advanced drug delivery systems, such as nanocarriers for growth factors, antibiotics, or anti-inflammatory agents. Nanocarriers can provide targeted and sustained release of therapeutic agents directly to the wound site [63]. PBM enhances cellular receptivity by increasing membrane fluidity and endocytosis, thereby facilitating more efficient uptake of the encapsulated drugs [64]. Additionally, PBM’s anti-inflammatory properties reduce the local inflammatory response, allowing for more effective utilization of antibiotics and growth factors without the interference of excessive inflammation [65]. This combination not only maximizes the therapeutic potential of the drugs but also minimizes potential side effects by ensuring precise delivery and controlled release.
PBM presents a versatile and effective approach to enhancing wound healing and skin regeneration. The studies summarized in Table 1 demonstrate PBM’s broad applicability and effectiveness across various clinical scenarios. PBM influences multiple cellular processes simultaneously, including fibroblast proliferation, angiogenesis, keratinocyte migration, collagen synthesis, and stem cell activation, positioning it as a comprehensive therapeutic modality. The non-invasive nature of PBM, combined with minimal side effects, enhances its clinical utility and patient acceptability. PBM’s capacity to modulate inflammation and oxidative stress is particularly beneficial in chronic wound conditions where persistent inflammation and oxidative damage impede healing. By creating a more favorable environment for tissue repair, PBM accelerates healing and improves the quality of the regenerated tissue, reducing the risk of scarring and enhancing functional outcomes.
While other emerging biotechnologies each offer unique advantages in promoting wound healing and skin regeneration, PBM distinguishes itself through its non-invasive nature, minimal side effects, and ability to simultaneously modulate multiple cellular pathways. Unlike PRP and stem cell therapies, which involve the extraction and manipulation of biological materials, PBM provides a straightforward application of light therapy without the need for invasive procedures. Additionally, PBM’s capacity to influence mitochondrial function, ROS levels, gene expression, and inflammation allows it to address multiple aspects of the healing process concurrently, potentially offering more comprehensive therapeutic benefits compared to therapies targeting specific pathways.
Moreover, PBM can be easily integrated into existing wound care protocols, requiring minimal training and equipment compared to more complex biotechnologies. Its versatility across different wound types and patient populations further enhances its clinical applicability. However, it is essential to recognize that these biotechnologies are not mutually exclusive and may offer synergistic benefits when used in combination with PBM, providing a multifaceted approach to optimizing wound healing and skin regeneration outcomes. For instance, combining PBM with PRP therapy or bioengineered skin substitutes could potentially enhance overall healing efficacy by leveraging the complementary mechanisms of each therapy [66].
Technological advancements in light delivery systems also hold significant potential for the future of PBM. The development of wearable PBM devices and portable, user-friendly equipment could facilitate more widespread and accessible use of PBM in both clinical and home settings. These innovations could democratize PBM therapy, making it available to a broader range of patients, including those in remote or underserved areas. Despite its promising potential, the widespread adoption of PBM faces several challenges that must be addressed. One of the primary obstacles is the lack of standardized treatment protocols. Variability in PBM parameters across different studies―such as wavelength, power density, treatment duration, and frequency―makes it difficult to compare results and establish universally accepted guidelines. Establishing standardized protocols through large-scale, multicentric clinical trials is essential for validating PBM’s efficacy and ensuring consistent therapeutic outcomes.
Another challenge is the need for a comprehensive understanding of PBM’s underlying mechanisms. While significant progress has been made in elucidating how PBM influences cellular processes, the intricate interplay between various molecular pathways and cellular responses remains to be fully understood. Further research is necessary to map out these interactions and identify the precise mechanisms by which PBM exerts its therapeutic effects. This deeper understanding could inform the optimization of PBM parameters and enhance its clinical application.
While competing biotechnologies such as PRP therapy, bioengineered skin substitutes, and growth factor therapy continue to advance, PBM distinguishes itself through its non-invasive nature, minimal side effects, and ability to modulate multiple cellular pathways simultaneously. This positions PBM as a complementary or alternative approach in various clinical scenarios, offering a versatile tool for clinicians seeking to optimize wound healing and skin regeneration outcomes.
Future research should focus on optimizing PBM treatment parameters, including wavelength, dosage, and treatment duration, to maximize therapeutic benefits. Additionally, large-scale clinical trials are necessary to validate PBM’s efficacy across diverse patient populations and wound types. Understanding the long-term effects of PBM and its integration with other regenerative strategies will further enhance its application in clinical practice. Addressing current limitations, such as standardization of protocols and large-scale clinical validation, will be essential for the widespread adoption of PBM in clinical practice.
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All work was done by KW.
No potential conflict of interest relevant to this article was reported.
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