Successful management of peri-implantitis remains a challenging task owing to its complexity [1]. During the surgical phase, the steps involved comprise the dental plaque and calculus removal, decontamination of dental implant surface, guided tissue regeneration, and eventually maintenance of health conditions [2]. Effective decontamination of the implant surface is a crucial and one of the most difficult steps. For this reason, numerous varying approaches have been used [3,4]. The surfaces of titanium implants can be decontaminated mechanically (i.e., air-powder abrasive, ultrasonic scalers, dental curettes) and/or chemically (i.e., EDTA, chlorhexidine digluconate, hydrogen peroxide, and citric acid), normally associated with systemic and local antibiotics [5,6]. However, some of these approaches may promote bacterial resistance or damage the surface characteristics of implants [7,8].

Several investigations have exhibited that the utilization of lasers might be helpful to decontaminate the surfaces of titanium implants. The most used lasers in peri-implant care include erbium, diode, and carbon dioxide lasers, owing to their bactericidal activity, selective calculus ablation, and hemostatic features [9,10]. However, undesirable temperature increases can be promoted by high-power lasers. The high cost of equipment is another limitation of such lasers [9,10].

Photodynamic therapy (PDT), also known as photochemotherapy, phototherapy, or photoradiation therapy, is a photochemical decontamination approach, which conjugates the utilization of low-level light energy with a photosensitizer (PS) as a non-toxic chemical agent in the presence of oxygen [11]. PDT is an extensively investigated treatment modality that is being widely employed for the treatment of numerous oral and systemic infections [12,13]. Moreover, PDT has been used in several clinical, in vivo, and in vitro studies as adjunctive therapy for the treatment of peri-implantitis and periodontitis [14], [15], [16].

Sonodynamic therapy (SDT), also known as sonodynamic antimicrobial chemotherapy, sonodynamically antibacterial chemotherapy, or sonodynamic chemotherapy, is an ultrasound intervention approach that has been revealed to be very efficacious in the killing of microorganisms [17,18]. Recent investigations have demonstrated satisfactory outcomes with SDT to inhibit microorganisms owing to its strong penetrating power via its activity propagation only when irradiation to ultrasound, no drug resistance, non-invasive capacity, and a sonochemical process [19,20]. SDT is an amalgamation of molecular oxygen, a sonosensitizer (SS), and ultrasound waves [21]. In SDT, microbubbles might generate via the acoustic cavitation procedure during the associations between target cells and ultrasound wave, which results in sonoporation [17]. The increased temperature, as a result of cavitation, might lead to the generation of reactive oxygen species (ROS) in the similar manner as in the PDT, which ultimately causes cell death [22].

The management of oral biofilm-related bacterial infections (such as peri-implantitis) poses challenges because of numerous antibacterial resistance mechanisms of oral biofilms [23]. The decreased susceptivity of oral biofilms derived from plaque to methylene blue (MB)-mediated PDT in vitro has also recently been exhibited [24]. Many probable explanations exist regarding the decreased susceptivity of biofilms to PDT, such as the expression of specific phenotypes by microbes within the biofilm [25], the presence of biofilm microbes in a starved or slow-growing condition [26], and the inactivation of the PS [27]. The limited infiltration of MB in biofilms [28] and the capability of bacterial cells to expel MB through multidrug resistance pumps [29] also play their part in the partial removal of biofilm microbes. A possible way of overcoming the latter two limitations is to formulate a delivery system that considerably enhances the pharmacological features of MB.

The authors of the current study hypothesized that MB-loaded poly(D,L-lactide-co-glycolide; PLGA) nanoparticles (NPs) either negatively or positively charged and having a diameter of less than 220 nm would demonstrate a higher photodynamic effect and might free MB in bacterial plaque suspensions together with in biofilms derived from plaque inocula. The NP matrix PLGA is a co-polymer of poly(glycolic acid; PGA) and poly(lactic acid; PLA), and has been approved by the Food and Drug Administration owing to its capability of degrading in the body via natural mechanisms and its biocompatibility [30]. PLGA NPs have been successfully utilized for the purpose of PSs’ drug delivery [31,32]. Once loaded inside PLGA, the quenching of the PS's excited state takes place, which leads to phototoxicity loss. On incubating the NPs with cells, a time-dependent release of the PS is demonstrated by the NPs, which later recaptures its phototoxicity and leads to an activated photodynamic nano-agent [33]. The published literature strongly suggests that the phototoxicity on bacteria and uptake is improved by the positive charge of a PS [34], [35], [36]. Hence, the present study aimed to evaluate the mechanical (i.e., flexural modulus [FM], flexural strength [FS], and surface roughness [Ra]) and antibacterial efficacy of photo-sonodynamic therapy via MB-loaded PLGA NPs over dental implants for potential treatment of peri-implantitis.