## 1 Introduction  
Peri-implant diseases are defined as inflammatory pathosis of the implant-surrounding tissues with an infectious origin, whose exacerbation follows the dysbiosis and impairment of the host immune response [1]. It can be distinguished into two different forms of peri-implant diseases: peri-implant mucositis, which is an inflammation of soft tissues around dental implants, and peri-implantitis, which is an irreversible inflammatory condition affecting both soft and hard (bone) implant-surrounding tissues, causing marginal bone loss if not treated [2].  
The recently published European Federation of Periodontology (EFP) guidelines for the prevention and treatment of peri-implantits clearly distinguish different phases for approaching the management of peri-implantitis [3]. The nonsurgical steps for the treatment of peri-implantitis should always include instructions and motivation for the patient for establishing and maintaining adequate oral hygiene, and the supramarginal and submarginal removal of dental biofilm through appropriate treatment protocols [3]. After this phase, a re-evaluation visit is fundamental for deciding whether the case should proceed with the surgical phase of treatment, if the endpoints of the nonsurgical treatment are not matched [3]. Currently, the local administration of antibiotics is not recommended, as associated with mechanical instrumentation for the treatment of periodontal diseases, based on systematic reviews of the literature [4; 5]. Interestingly, none of the studies used for providing such a recommendation were about the use of locally derived doxycycline. Doxycycline is an antibiotic belonging to the tetracycline family that may inhibit bacterial growth by acting through the inhibition of the protein synthesis of the bacteria. It is widely used for treating infections of the respiratory tract and of the urinary tract, and to treat oral infectious diseases [6].  
Local applications of doxycycline could be considered for the treatment of periodontal diseases as an adjunct to nonsurgical mechanical instrumentation, as reported in a systematic review used for the implementation of the European Federation of Periodontology Guidelines [7]. Locally delivered tetracycline was also used for the treatment of peri-implantitis associated with surgical procedure, as described in the study by [PERSON] et al., published in 2018, in which the application of doxycycline was performed in conjunction with the enamel matrix derivative and regenerative procedures [8]. In the cited study, the authors observed a significant improvement, on average, in all clinical and radiographic parameters. Another published case reported the use of a bioresorbable polymer that can release doxycycline over time, in conjunction with autogenous bone for the treatment of peri-implantitis [9].  
Regarding the use of the local administration of doxycycline for the treatment of peri-implant diseases, due to the lack of scientific evidence on the topic, and considering the risk of inducing bacterial resistance in patients with peri-implantitis [10], there is a need, in the opinion of the authors, for a scientific appraisal of the efficacy of such a treatment approach. In particular, the scientific literature does not provide, to our knowledge, a review about the efficacy/effectiveness of the local application of such an antibiotic, providing data about the scientific robustness of its use.  
For this reason, the aim of the present systematic review of the literature is to evaluate the efficacy of the local application of doxycycline gel as a monotherapy or in conjunction with another treatment as compared, if possible, with other treatment strategies when used for the treatment of peri-implant diseases and conditions.