Dental diseases are complex conditions initiated by microbial biofilm development in the oral cavity. One major clinical issue is their limited response to antimicrobial therapies. Additionally, there is potential for synergistic pathogenicity from the microorganisms they harbor contributing significantly to the pathogenesis of dental caries and periodontal diseases¹.

Various preventive and therapeutic strategies are currently used to treat these disorders. Local, regional drug treatments for microbial infections concentrate antimicrobials on the localization of infection and reduce systemic exposure. However, overuse of these drugs has caused resistant strains of bacteria to develop, creating a need for alternative antimicrobial approaches².

Indeed, while many traditional surgical procedures are proven and economical, numerous well-designed clinical trials show the beneficial effect of more focused therapies that may lead to better or at least equal success rates. Targeted therapies, which directly affect the cellular alterations supporting the pathogenicity of microbial growth, virulence and division, are increasingly integrated into localized dental treatments within the precision medicine paradigm. Further development of these well-targeted therapies is being facilitated by ongoing efforts in research that offer the promise of developing more effective and precise treatment modalities³.

The term 'photodynamic therapy' originated in 1900 when Oscar Raab discovered that a combination of acridine dye, visible light, and oxygen could kill paramecia. PDT is characterized as killing target cells by reactive oxygen species (ROS) generated by activating a photosensitizing chemical by the light of a specific wavelength⁴. Photodynamic therapy uses three non-toxic agents: visible light, a photosensitizer, and oxygen. The principle of PDT is that the photosensitizer can selectively bind to the target cells and then be activated by light at the proper wavelength. When excited, the photosensitizer generates singlet oxygen and other cytotoxic reactive species toward bacteria and diseased cells. The photosensitizer is administered topically to the targeted area or via interstitial injection. The light used for activation has to be of a determined wavelength and at a relatively high intensity.

Collimated, coherent, and monochromatic laser light was developed in the 1970s and greatly promoted PDT. This therapy involves irradiating the diseased tissue with uniform low-energy laser light for effective activation. In this regard, PDT has also been called antimicrobial photodynamic therapy (PDT) or photodynamic antimicrobial chemotherapy.

Previous studies have established that PDT is simple to carry out and has an efficient and beneficial bactericidal action in dentistry. The antimicrobial effect can also be precisely regulated by varying the light dose, enabling rapid and localized eradication of the bacteria in a safety profile⁵.

MECHANISM OF ACTION OF PHOTODYNAMIC THERAPY

The bactericidal mechanism of photodynamic therapy involves two primary pathways: the generation of cytotoxic species that will damage bacterial DNA and the cytoplasmic membrane. Such effects can cause the inactivation of membrane transport systems, a decline in plasma membrane enzyme activities, lipid peroxidation, and other harmful processes. While it has been mentioned that antimicrobial photodynamic therapy causes DNA damage, damage to the cytoplasmic membrane through photochemical reactions is assumed to be the primary mechanism for bacterial killing⁶.

When irradiated with light of a specific wavelength (e.g.,  lasers), the photosensitizer is excited from the ground to a highly energized triplet state. The relatively long lifetime of the triplet state enables the excited photosensitizer to contact other nearby molecules. This process is believed to correlate with generating cytotoxic species in photodynamic therapy. Upon interacting with matter, a triplet-state photosensitizer can undergo two types of reactions, Type I and Type II ⁷.

In Type I reactions, hydrogen-atom abstraction, or electron-transfer reactions between the excited photosensitizer and an organic substrate molecule, occurs within the cells. This process generates free radicals and radical ions that interact with endogenous molecular oxygen to produce reactive oxygen species (ROS), including superoxide, hydroxyl radicals, and hydrogen peroxide. These ROS impair the integrity of the cell membrane, resulting in irreversible biological damage.

The Type II reaction involves a direct response of the photosensitizer in the triplet state with oxygen to yield an excited, highly reactive species of oxygen termed singlet oxygen. Because of its high chemical activity, singlet oxygen can react with many biological substrates and exert  oxidative damage, causing a lethal effect on bacterial cells by destroying the cell membrane and cell wall.

Microbes sensitive to singlet oxygen are viruses, bacteria, protozoa, and fungi ⁴. Singlet oxygen in biological systems has an extremely short lifetime (<0.04 µs) and a limited radius of action (0.02 µm). Due to the brief life and limited diffusion of the singlet oxygen, the site of initial cellular injury closely correlates with the distribution of the photosensitizer. This localization ensures targeted treatment without affecting distant tissues, cells, or organs⁸.

It seems that the main cytotoxic species responsible for the biological effects of photo-oxidative reactions is the singlet oxygen. Thus, antimicrobial photodynamic therapy predominantly comprises a Type II reaction,  which is universally accepted as the primary pathway involved in microbial cell death⁹.

PHOTODYNAMIC THERAPY (PDT) IN PERIODONTOLOGY: PERIODONTITIS, PERI-IMPLANTITIS AND HALITOSIS.

Photodynamic therapy (PDT) is a non-invasive, microbial, and area-sparing method for treating periodontitis, peri-implantitis, and halitosis. The continuous improvement in PDT's therapeutic efficacy, driven by technological advances, makes it a promising as an adjunctive or alternative therapy in periodontal treatment.

PDT in Periodontitis

Periodontitis is a chronic inflammatory disease starting from dysbiotic biofilms (e.g., Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans) that leads to progressive bone and tooth loss. Conventional scaling and root planing (SRP) may not eradicate subgingival pathogens. When PDT is applied, specifically in the treatment of periodontitis, it improves bacteria removal by targeting antibiotic-resistant strains and photosensitizers, like methylene blue (MB) and indocyanine green (ICG), shown to have strong antibacterial activity against periodontal pathogens. A study on chronic periodontitis reported significant reductions in probing depth (PD) and gains in clinical attachment level (CAL). In an RCT, patients treated with SRP + PDT (methylene blue + 660 nm diode laser) showed a PD reduction of 1.5–2 mm and CAL gain of 1–1.5 mm at the end of 6 months compared to SRP alone¹⁰.

When used adjunctively with SRP, PDT is effective against mature and highly dysbiotic biofilms, providing superior clinical outcomes compared to SRP monotherapy. In addition to antimicrobial action, PDT participates in the host immunomodulation by decreasing pro-inflammatory cytokines (IL-1β, TNF-α, for example) and increasing healing-related cytokines¹¹.

Conventional PDT in periodontitis is limited as photosensitizers penetrate deep periodontal pockets and dense biofilms poorly. In particular, NP-based delivery systems like chitosan-coated methylene blue for subgingival penetration, biofilm uptake, and antimicrobial activity increased penetration into the biofilm. The (nanoparticles) NPs are also capable of binding to bacterial membranes and (extracellular polymeric substances) EPS,  which enhances the delivery of photosensitizers to pathogens and has been demonstrated in P. gingivalis and A. actinomycetemcomitans¹².

Recent advances also indicate that antimicrobial blue light (BL 400–470 nm) can enhance PDT efficacy without needing external photosensitizers since it activates endogenous bacterial porphyrins. This allows for either photosensitizer-free or reduced-photosensitizer strategies with fewer side effects and the potential to maintain effective biofilm disruption¹³. Compared with SRP alone, enhanced PD reduction (up to 2.5 mm) and 90–95% pathogen clearance has been observed with multiple PDT sessions (2–4) over 3 months.

PDT in Peri-Implantitis:

A Strategy for Stabilization of Biofilm for Docile Implants

One major challenge to resolve is the peri-implantitis related to bone loss and biofilm formation surrounding the implants, which are difficult to decontaminate in professional settings.

PDT has multiple advantages compared with conventional mechanical and chemical modalities:

• An efficient eradication of Streptococcus mutans and Fusobacterium nucleatum species from titanium substrates.
• Osteoblast viability preservation vs. hydrogen peroxide or aggressive lasers that can damage the surrounding bone.
• Advanced re-osseointegration: one animal study stated 30% more bone regeneration when PDT was used adjunctively¹⁴.

Novel Developments: Beyond antimicrobial activity, PDT recently integrated bioactive photosensitizers such as curcumin, which are characterized by their immunomodulatory and bone-regenerative effects ²². When delivered by nanoparticles, these agents are promising candidates for treating periodontitis without interfering with tissue repair responses to periodontitis.

Another practical approach proposed for decontaminating rough implant surfaces is Er: YAG laser-assisted PDT. It integrates mechanical debridement and chemical disinfectant without forming deposits (unlike metal scalers). Er: YAG Laser (2940 nm) and PDT (methylene blue + IR 660 nm diode laser) penetrate the residual biofilms to eliminate the recalcitrant anaerobes15.

Halitosis: Killers of Volatile Sulphur Compound (VSC)-Producing Microbes

Halitosis, or oral malodor, is primarily due to anaerobic bacteria (e.g., Fusobacterium, Prevotella) on the tongue dorsum. When PDT is combined with periodontal therapy, a 70–85% reduction in VSCs and long-lasting improvement in breath have been observed. However, traditional techniques such as tongue scraping and mouthwashes provide only temporary benefits, while PDT provides prolonged antibacterial action.

Key developments include:

• 3 months, 80% VSC reduction with Toluidine Blue O (TBO)-based PDT
• Chlorophyllin-PDT (excited with red LED lights) destroys odor-inducing bacteria and spares the beneficial salivary flora.
• Probiotic-PDT combinations such as Lactobacillus reuteri + photosensitizer restore the microbial balance post-treatment¹⁶.

PHOTODYNAMIC THERAPY IN ENDODONTICS

Photodynamic therapy (PDT) has recently been proposed as a promising adjunctive antimicrobial system in clinical endodontics. This is based on the interaction of a non-toxic photosensitizer (PS) excited by light in the presence of oxygen, leading to reactive oxygen species (ROS) that damage microbial cells^17,18. This procedure has reported promising results against resistant biofilms and persistent endodontic pathogens like Enterococcus faecalis, a commonly involved organism in endodontic failure analysis¹⁹.

PDT is typically used alongside conventional irrigants such as sodium hypochlorite (NaOCl) and chlorhexidine (CHX), enhancing disinfection efficacy, especially in inaccessible areas of the root canal system, where mechanical instrumentation cannot reach. Methylene blue and toluidine blue are common photosensitizers excited under red light (630–700 nm) to facilitate deeper tissues^18,21. Compared to conventional bleaching strategies, PDT is effective against planktonic bacteria and mature biofilms while having low cytotoxic effects^18,23.

Notably, PDT has exhibited efficacy against antibiotic-resistant bacterial strains and has not led to the emergence of microbial resistance^19,22. In addition to this, it serves as a less harmful alternative to strong chemical irrigants because of its ability to facilitate disinfection within complex root canal anatomies and dentinal tubules²⁰. Additionally, under clinical conditions, PDT has demonstrated a high biocompatibility and safety profile with a low risk of damaging effects^18,23.

As a result, the clinical extent of PDT adoption in endodontics is limited by the absence of standardization of protocols. Indeed, each study utilizes different parameters for variables such as the type of photosensitizer, its concentration, parameters of the light source, and light exposure time^17,21,24. Such variation complicates comparative research and underscores the necessity for subsequent, standardized clinical investigations ^20,24.

Despite these drawbacks, PDT is highly promising as a minimally invasive and biocompatible disinfection approach. However, its potential will only be fully realized through large-scale clinical trials assessing long-term outcomes, efficacy, and cost-effectiveness¹⁷.

Photodynamic Therapy in Conservative Dentistry: A Targeted Approach Towards Caries and Biofilm Management.

Dental caries is a common and multifactorial disease that affects people of all ages, but especially children and the underserved²⁵. Acid generated by microbial biofilms causes the demineralization of tooth structure. Traditional management usually requires significant mechanical removal of carious material, which may jeopardize the vitality and structural integrity of the tooth. To this end, conservative dentistry is characterized by relying on minimally invasive techniques that respect healthy tooth structure and maintain pulp vitality²⁶. Among recent adjunctive therapies, antimicrobial photodynamic therapy (PDT) is one therapy that has attracted attention due to its selective antimicrobial activity against cariogenic microorganisms and its ability to preserve the conservation of affected dental tissues²⁷. In this method, a biocompatible photosensitizer is first applied and then activated by light in an oxygen-containing environment, producing reactive oxygen species (ROS) that can attack and kill bacterial cells²⁸. It fits nicely into the rules of conservative dentistry, as it provides an efficacious, relatively non-invasive, and biologically compatible means to deal with early carious lesions and biofilms.

Mechanism and Photosensitizers

PDT employs photosensitizers (e.g., methylene blue, toluidine blue, curcumin, or indocyanine green), which generate cytotoxic singlet oxygen and other reactive oxygen species after the light of the appropriate wavelength excites them. These species can damage bacterial membranes, proteins, and nucleic acids²⁸. These include methylene blue and toluidine blue, which are activated by red light (~630–660 nm) and are the most widely used due to their deep tissue penetration and strong antimicrobial effect²⁹. Furthermore, curcumin and indocyanine green have extrinsic antioxidant and anti-inflammatory effects, extending the therapeutic impact of a PDT²⁸.

PDT IN THE MANAGEMENT OF CARIES

Selective caries removal is a standard approach used in conservative dentistry to retain partly demineralized, remineralizing dentin. Alves et al. assessed PDT as an adjunct to this method in a randomized clinical trial on children, observing a significant bacterial reduction (92.6% for the PDT group vs. 76.4% for the control group treated by mechanical excavation only)²⁵. The clinical performance of restorations placed, following PDT was comparable between groups, and adverse effects were not observed after 6 months of follow-up. In accordance, Melo et al., through an in vivo rat model, showed that PDT, which combined toluidine blue and red light, reduced Streptococcus mutans counts early in enamel demineralization, significantly inhibiting the progression of carious lesions²⁶. Thus, PDT may have a preventive ability in carious lesions and may be used alongside conventional fluoride preventive methods.

PDT IN BIOFILM MANAGEMENT ON DENTIN AND ENAMEL

Oral biofilms are complex multispecies communities capable of acid production and therefore, the initiation of caries. Cieplik et al. and Baptista et al. highlighted the effectiveness of different photosensitizing agents, such as curcumin and methylene blue, in dislodging preformed biofilms on enamel and dentin surfaces ^27,28. Curcumin-mediated PDT, using blue light as an activator, significantly reduced microbial viability within biofilms with low cytotoxicity to host tissues²⁷. This demonstrates its importance in controlling early non-cavitated lesions and the residual biofilm left after the excavation phase. Cieplik et al. conducted a thorough review to substantiate the relevance of PDT in controlling the biofilm involved in caries, mainly since it can be used instead of conventional antimicrobial agents, which can lead to the development of resistance ²⁶. They also emphasize the need for more in vivo trials to standardize protocols and long-term outcomes.

Management of Precancerous and Cancerous Lesions

Photodynamic therapy (PDT) has evolved as a minimally invasive and highly selective therapeutic modality in the management of potentially malignant oral disorders (OPMDs) and selected early-stage oral cancers. PDT is based on generating reactive oxygen species (ROS) produced by the interaction of a photosensitizing agent, a defined wavelength of light, and tissue oxygen³¹. This reaction produces selective cytotoxicity to dysplastic and malignant cells but preserves adjacent healthy tissue. This degree of selectivity is particularly beneficial in functionally crucial anatomical locations such as the tongue, buccal mucosa, and floor of the mouth ³².

The light source, which is non-invasive and therapeutic, emits light wavelengths chosen carefully to match the absorption spectrum of the photosensitizer. This results in ROS production, leading to apoptosis of tumor cells and disrupting tumor vasculature to improve the inflammatory and immune response. PDT has shown clinical efficacy in treating common OPMDs, including oral leukoplakia and erythroplakia. Notably, Chen et al. (2007) and later reports showed CRs of between 60% and 90%, especially among non-homogeneous lesions where photosensitizer accumulation can be improved. Compared to traditional treatments like CO₂ laser ablation or surgical excision, PDT appears to achieve similar CR rates but with improved oral function preservation and reduced recurrence rate. Recurrence rates after PDT remain at 15–30% for two years. Moreover, patients who undergo PDT experience less scarring, maintain their speech and swallowing functions, and have a less painful postoperative course, which makes PDT a candidate for first-line therapy, particularly for broad and multifocal lesions³³.

T1/T2 tumors have shown promising results in the early stage of OSCC (oral squamous cell carcinoma) with a CR rate from 70% to 90% using PDT. This is particularly advantageous for patients with systemic comorbidities, making them ineligible for surgery or in whom tissue preservation is essential. However, the shallow penetration of PDT (5–10 mm) limits its therapeutic effect on superficial lesions³⁴. To overcome these limitations, adjunctive modalities like interstitial photodynamic therapy utilizing fiber-optic delivery systems and combinatorial strategies with immuno-oncology are being actively explored.

The possibility of performing PDT repetitively at the same site without cumulative toxicity is an advantage of PDT over surgery and radiotherapy. In addition, its usage is not limited to the oral cavity but expands to other cancers like early gastrointestinal and esophageal cancers and lung cancer³⁵. Other recent data indicate that it can evoke antitumor immune responses. In particular, decreased distant metastasis has been associated with using checkpoint inhibitors such as pembrolizumab in a combinatorial therapy setting. Additionally, this synergy is being studied for its ability to target resistant populations of tumor cells³⁶.

Although PDT does have some advantages, it also has some limitations. Clinical challenges include adverse effects (e.g. photosensitivity reactions), the potentially high costs of photosensitizers, and variable efficacy indexed to lesion characteristics. Due to poor penetration of drugs under hyperkeratotic lesions, mechanical debridement is often needed before treatment³⁷. However, innovations like nanoparticle-augmented photosensitizers and advanced light delivery systems also mitigate these disadvantages. Moreover, the smart nanoplatforms with synergistic antitumor mechanisms showed even greater therapeutic effects than the two-drug combination therapy ³⁸.

In conclusion, PDT is changing how we conservatively manage OPMDs and some early OSCC patients. This synergy of high effectiveness with low invasiveness, functional sparing, and repeatability establishes it as a powerful option for standard surgical and radiotherapies. The evolution of photodynamic therapy (PDT), incorporating nanotechnology and microbiome-modulated strategies, represents a significant advancement in palliative care and the enhancement of survival outcomes for patients with advanced, non-resectable head and neck cancers. PDT is increasingly recognized as a critical modality within multidisciplinary management frameworks for head and neck oncology.

PHOTODYNAMIC THERAPY IN TEMPOROMANDIBULAR DISORDERS AND OROFACIAL PAIN

Temporomandibular disorders (TMDs) refer to disorders of the temporomandibular joint (TMJ),  its surrounding musculature, and associated bony structures. Commonly, these conditions are found among younger and middle-aged adults, usually between the ages of 20 and 40 years, exhibiting symptoms that include jaw loading,  pain, facial pain, and chronic headaches³⁹. TMD is a multifactorial process with possible causes involving aberrant masticatory patterns, dental malocclusions, psychological stress, post-traumatic alteration of the joint, and morphologic changes⁴⁰.

Most mild cases are self-limiting and may not require clinical management, but a more severe presentation may require therapeutic intervention. Clinical Degree-Of-Effectiveness has suggested modalities such as iontophoresis, phonophoresis, hypnosis, acupuncture, and behavioral therapy with ≥ 10% but < 50% efficacy. Oral splints have previously been recommended, but the evidence to support this treatment approach is not clear⁴¹. In non-responsive cases, invasive techniques such as intra-articular steroid injection or maxillo-facial surgery, including joint replacement, might be necessary ⁴².

Advancements now implicate photodynamic therapy (PDT) as a promising alternative therapy for the treatment of TMD and related orofacial pain. PDT consists of exposing a photosensitizer to the light of certain wavelengths, which leads to the generation of reactive oxygen species (ROS) that address inflammation and promote tissue healing⁴³. Red light (633 ± 10 nm) penetrates deeper into tissues, reducing inflammation, and blue (417 ± 10 nm) and yellow (590 ± 10 nm) light have previously been used to relax muscle tension. Medium tissue penetration according to blue light (absolutely pretty shallow penetration) and red light (so deep penetration) with respective wavelengths of 70±20 nm and 633±10 nm, respectively. In summary,  blue and yellow light work well on muscle relaxation, and red light can penetrate deeper tissues and is anti-inflammatory. These effects, based on specific wavelengths, further demonstrate the capability of PDT to target multifactorial aspects of TMD⁴⁴.

A 2014 multicenter randomized controlled trial compared the effects of phototherapy (LLLT or low-level laser therapy and LED therapy) for TMD-associated muscle pain. Seventy-two healthy, non-pregnant females aged 18–40 participated in the study, recording clinical parameters in a double-masked method, such as electromyography (EMG), visual analog scale (VAS) scores, algometry, and phototherapy response. The study focused on the cumulative effect of phototherapy on symptomatic relief, with four sessions included. While results are not yet available,  the trial demonstrates increasing interest in light-based therapies for TMD. Melis et al. performed a systematic review (2012) highlighting the methodological heterogeneity of studies investigating LLLT and urged standardized procedures and more high-quality research⁴⁵.

The most recent retrospective study (2022–2024) directly compared the use of intra-articular injections with PDT for TMD treatment. A total of 91 individuals were included in the study, of whom 45 were assigned to the control group receiving injections and 46 to the PDT group. All the candidates were assessed using standard outcome measures such as the VAS scoring. Red, blue, and yellow light wavelengths were used to deliver PDT, and any additional modalities associated with pain relief were limited.

At the one-month follow-up, both groups had symptomatic improvement, but PDT had better pain reduction, joint movement, and muscle recovery. It concluded that the long-lasting therapeutic effects of PDT suggest that it may be instrumental in managing patients with complex TMD and represents a non-invasive, repeatable, effective intervention.

Thus, photodynamic therapy represents a promising treatment modality for TMD and orofacial pain, especially in patients who are reluctant to undergo invasive procedures ⁴⁴. With its impacts on inflammation, muscle tension, and tissue healing, it serves as a modern adjunct to maxillofacial non-surgical practices' pain-free state.

Photodynamic therapy (PDT) represents a potential methodology in dentistry, but the transition from laboratory to clinical work is associated with numerous obstacles and limitations. Addressing these challenges is critical for advancing PDT and maximizing its potential in oral healthcare.

Opportunities and Limitations

46. Shallow tissue penetration: One of the main constraints of PDT is the limited penetration depth of visible light in biological tissues. Konopka and Goslinski pointed out that this limitation restricts action to superficial lesions and infections of the oral mucosa and outer layers of the periodontium. It is less effective in deeper infections that might arise in root canals or chronic periodontal disease⁴⁶.
47. Selectivity and Delivery of Photosensitizers: As stated by Konopka and Goslinski, one of the critical challenges remaining is to achieve selective accumulation of photosensitizers in the target cells (e.g.,  bacteria, fungi, or malignant cells), preventing uptake in adjacent healthy tissues. Skin photosensitivity may last long after that exposure, and the effective delivery of first-generation photosensitizers to specific target sites in the oral cavity, such as periodontal pockets or root canals, maybe cumbersome⁴⁶.
48. Oxygen Dependence: Soukos and Goodson underscored the importance of molecular oxygen as the precursor of cytotoxic reactive oxygen species (ROS) that are responsible for successful PDT, and that hypoxic conditions often found in oral infections and tumors may limit the effectiveness of PDT⁴⁷.
49. Light Delivery: As Konopka and Goslinski noted, delivering the appropriate light wavelength and intensity to the target site,  particularly in an anatomically complex area such as the oral cavity, represents a significant technical challenge ⁴⁶.
50. Cost and Accessibility: The expense associated with PDT equipment, such as lasers or other specialized light sources, and the requirement for specialized training may restrict accessibility among practitioners and patients alike.
51. Absence of Uniform Protocol: Soukos and Goodson write that PDT has no standardized treatments. Differences in photosensitizer type, concentration, light source parameters, and treatment duration have been attributed to inconsistent comparisons and limited guideline decisions ⁴⁷.
52. Biofilms: Garcez et al. detailed that biofilm, i.e., highly resistant microbial communities, reduce the effect of PDT ⁵⁵. This has particular significance in the management of periodontitis and endodontic infections⁴⁸.
53. Periodontal Diseases: In periodontal diseases, Meisel and Kocher explored PDT and noted that consistent, long-lasting outcomes were difficult to obtain, especially in advanced cases ⁴⁹.
54. Endodontic Infections: Fimple et al. investigated PDT for endodontic infections and commented on the difficulties presented by complex root canal systems with diverse microbial flora and low light penetration⁵⁰.

FUTURE DIRECTIONS

To address these limitations and further extend the applications of PDT within the field of dentistry, future studies should be directed toward:

• Development of Novel Photosensitisers: The group of Wainwright et al proposed the design of a new generation of photosensitizers with greater specificity for the target cells and a favorable tissue penetration depth (e.g., near-infrared activation), reduced toxicity to healthy tissue cells, improved biocompatibility, and use of nanoparticle-containing delivery systems⁵¹.

1. Advanced Varieties of Light Delivery Systems: Future innovations will use optical fibers and waveguides for otherwise inaccessible regions (such as root canal applications), LED-based devices with variable parameters, and image-guided PDT to enhance the precision of target regions, thereby minimizing collateral damage⁴⁶.
2. Combination Therapies: The synergistic use of PDT with other treatments, such as mechanical debridement, antimicrobial agents, and even immunotherapy, has improved treatment outcomes. PDT appears to be helpful as an adjunct to scaling and root planing in periodontal therapy.
3. Counteracting Hypoxia: New approaches, such as oxygen-loaded nanoparticles and hypoxia-sensitive photosensitizers, help increase PDT effectiveness in hypoxic conditions ⁴⁷.
4. Clinical Trials and Standardization: Large-scale, well-designed, standardized clinical trials are urgently needed to facilitate the safe and effective incorporation of PDT into everyday dental practice⁴⁷.
5. Artificial Intelligence (AI) and PDT: AI plays a significant role in PDT optimization, assisting in treatment planning, ensuring the appropriate light dose, and selecting photosensitizers.
6. PDT vs. Photobiomodulation: Konopka and Goslinski pointed out that photobiomodulation (low-level laser therapy) ought to be differentiated from PDT. Both use light, but photosensitizers and ROS generation are only associated with PDT; the influence of photobiomodulation on cellular activity is non-cytotoxic46.

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