7.1 Biological Rationale

Periodontitis is a bacterial biofilm–caused oral disease associated with loss of the supporting tissues (i.e. periodontal ligament and alveolar bone) around the tooth (Page and Kornman 1997). Therefore, the main objective of periodontal therapy is the removal/destruction of the supra‐ and subgingival biofilm from the root surface to stop or slow down disease progression (Cobb 1996). A plethora of studies have provided evidence for the clinical efficacy of nonsurgical periodontal treatment, and therefore, it is considered to be the key part of cause‐related periodontal therapy and maintenance (Badersten et al. 1981; 1984; Lindhe et al. 1984).

Nonsurgical periodontal treatment is usually performed by means of power‐driven instruments, curettes, or a combination thereof and, in the great majority of cases, is sufficient to reestablish periodontal health. However, under certain clinical circumstances, such as persistent deep periodontal pockets with or without infrabony defects or pockets located in the furcation area of multirooted teeth, nonsurgical subgingival instrumentation may not be sufficiently effective to adequately eliminate/disrupt the subgingival bacterial biofilm and calculus (Drisko 1998; Adriaens and Adriaens 2004; Umeda et al. 2004). At these sites, mechanical debridement alone is insufficient to eliminate some “key note” pathogens, such as Aggregatibacter actinomycetemcomitans (A.a.) (Rudney et al. 2001) and/or Porphyromonas gingivalis (P.g.) (Bostanci and Belibasakis 2012), which have been shown to possess the ability to penetrate in the surrounding soft tissues. In such complex clinical situations, in order to optimize the clinical outcomes, topical or systemic antibiotics may be used (Bonito et al. 2006; Keestra et al. 2015a, b).

However, although antibiotics have been shown to be efficient in reducing or eliminating periodontal pathogens, their use may be associated with a number of side effects, including skin rash, itching, oral candidiasis, or gastrointestinal problems such and nausea or vomiting (Gillies et al. 2015) and may comport the risk to increase bacterial resistance, a growing public health issue with substantial economic and social consequences (Rams et al. 2014; Olsen 2015). Thus, there is an obvious need for developing new treatment alternatives with fewer side effects, but with the potential to effectively reduce or eliminate bacterial biofilms (Grzech‐Lesniak 2017).

Photodynamic therapy (PDT), also termed photoradiation therapy, phototherapy, photochemotherapy, photo‐activated disinfection (PAD), or light‐activated disinfection (LAD), was introduced in medical therapy in 1904 as the light‐induced inactivation of cells, microorganisms, or molecules and involves the combination of visible light, usually through the use of a diode laser and a photosensitizer (von Tappeiner 1904).

The photosensitizer is a substance that is capable of absorbing light of a specific wavelength and transform it into useful energy. When used alone, neither of the two components (i.e. photosensitizer and light) is harmful. However, when combined they can lead to the production of lethal cytotoxic substances which can selectively destroy bacteria or cells (Sharman et al. 1999). Therefore, PDT has been proposed as a modality to reduce bacterial load or even to eliminate periodontal pathogens (Wilson et al. 1992; Pfitzner et al. 2004).

Most frequently, diode lasers of a wavelength between 635 and 670 nm are used, although in some studies also wavelengths of 808 nm (Dilsiz et al. 2013) and 940 nm have been also tested (Lui et al. 2011).

The most commonly used photosensitizers in the treatment of periodontal and peri‐implant therapy infections are methylene blue (MB) and toluidine blue (TB) (Romanos and Brink 2010; Noro Filho et al. 2012; Bassir et al. 2013; Javed and Romanos 2013; Schär et al. 2013). The two substances have similar chemical and physicochemical characteristics and have been demonstrated to be effective against both Gram‐positive and Gram‐negative bacteria (Kikuchi et al. 2015; Olsen et al. 2017).

Ideally, following its application, the photosensitizer should remain for a period of 1–5 minutes in the periodontal and peri‐implant pockets followed by irradiation with wavelengths between 630 and 660 nm, respectively (Chan and Lai 2003; Kikuchi et al. 2015).

On the other hand, when green‐colored photosensitizers such as indocyanine green are used, the irradiation wavelength is 805 nm (Nagahara et al. 2013).

The action mechanism of PDT has been extensively described (Dougherty et al. 1998). Briefly, upon illumination the photosensitizer is excited from the ground state to the triplet state. The longer lifetime of the triplet state enables the interaction of the excited photosensitizer with the surrounding molecules. It is anticipated that the generation of the cytotoxic species produced during PDT occurs while in this state (Moan and Berg 1991; Ochsner 1997).

The cytotoxic product, usually singlet oxygen (¹O₂), cannot migrate at a distance of more than 0.02 μm after its formation, thus making it ideal for local application of PDT, without endangering distant molecules, cells, or organs (Moan and Berg 1991).

During the last two decades, a considerable interest has evolved in evaluating the use of PDT in the treatment of periodontal and peri‐implant infections.

In patients with untreated periodontitis, treatment with subgingival scaling and root planing (SRP) followed by subsequent application of PDT may lead to statistically significant higher improvements in probing depth (PD) reduction and/or clinical attachment (CAL) gain than following SRP alone (Andersen et al. 2007; Braun et al. 2008; Sigusch et al. 2010; Al‐Zahrani and Austah 2011; Dilsiz et al. 2013; Betsy et al. 2014; Alwaeli et al. 2015), while other studies have failed to reveal statistically significant differences in these parameters (Christodoulides et al. 2008; Polansky et al. 2009; Ge et al. 2011; Lui et al. 2011; Theodoro et al. 2012; Balata et al. 2013; Luchesi et al. 2013; Queiroz et al. 2015).

A frequently observed outcome following the use of PDT was additional improvement in terms of bleeding on probing (BOP), thus pointing to the potential effects of this treatment on reducing periodontal inflammation (Christodoulides et al. 2008; Polansky et al. 2009; Ge et al. 2011; Lui et al. 2011; Theodoro et al. 2012; Balata et al. 2013; Luchesi et al. 2013; Queiroz et al. 2015). However, it is interesting to note that despite the obtained clinical improvements, changes of microbiological parameters were only found in some of the studies (Braun et al. 2008; Christodoulides et al. 2008; Sigusch et al. 2010; Ge et al. 2011; Alwaeli et al. 2015).

A very recent systematic review has investigated the adjunctive effects of PDT application to nonsurgical mechanical instrumentation. Only studies including at least 20 patients with untreated periodontitis and with a follow‐up period of six months were included, while PDT has only been used once after mechanical debridement. The results failed to reveal statistically significant additional clinical improvements following a single application of PDT to nonsurgical mechanical instrumentation compared to mechanical debridement alone (Salvi et al. 2019).

However, in periodontal patients enrolled in a maintenance program (i.e. patients with treated periodontitis), the additional application of PDT to mechanical debridement has been shown to stabilize tissue inflammation, evidenced by higher values of BOP reduction (Chondros et al. 2009; Lulic et al. 2009; Cappuyns et al. 2012; Campos et al. 2013; Kolbe et al. 2014; Petelin et al. 2014; Muller Campanile et al. 2015).

Increasing evidence also suggests that in periodontal patients enrolled in maintenance, the repeated application (i.e. two, three, or even five times) of PDT to mechanical debridement may yield better outcomes in terms of pocket depths and inflammation (i.e. BOP), compared to single applications (Lulic et al. 2009; Muller Campanile et al. 2015; Grzech‐Leśniak et al. 2019).

A very recent study has evaluated clinically and microbiologically the outcomes following one single session of subgingival mechanical debridement (scaling and root planing; e.g. SRP) followed by 1× immediate use of PDT and 2 × subsequent use of PDT without SRP. Forty patients diagnosed with generalized chronic periodontitis who were enrolled in a periodontal maintenance (recall) program were randomly assigned to one of the two treatments: (i) SRP by means of ultrasonic and hand instruments followed by one single session of SRP followed by 1× immediate use of PDT and 2 × subsequent use of PDT without SRP (test) or (i) SRP alone (control) (Grzech‐Leśniak et al. 2019).

The results revealed that both treatments improved statistically significantly in most of the evaluated parameters. In the test group, BOP decreased statistically significantly (p < 0.05) after three and six months, while in the control group the respective values decreased statistically significantly only at three months. The results have provided additional evidence of the potential clinical benefit of repeated PDT applications indicating that the repetition of this treatment may additionally improve clinical outcomes, in particular the gingival inflammation evidenced by a decrease in BOP (Figures 7.1