## 1 Introduction  
Recurrent aphthous stomatitis (RAS) is an inflammatory disease with a multifactorial and immune-mediated etiology whose clinical manifestation is associated with recurrent ulcerations of the oral mucosa [1, 2]. This pathology is documented as one of the most frequent diseases of the oral cavity, affecting around 10-20% of the population, especially between the second and third decade [3, 4]. RAS has recurrent evidence that shows periods of quiescence following phases of exacerbation with a moderate tendency to decrease in frequency and severity in the following decades [5, 6]. An individual predisposition can sometimes generate the presentation of recurrent lesions even in adulthood, especially if associated with systemic disorders or states of immunodegression [2, 5, 7]. Several factors have been detected for RAS including local trauma, microbiological activity, hypersensitivity, immunological and hormonal disorders, and vitamin deficiencies such as zinc, iron, vitamin B1, B2, B6, B12, folic acid, and beta-blockers, bisphosphonates, NSAIDs, protease inhibitors, and sulfonamides [4; 5; 6; 8; 9; 10; 11]. Moreover, syndromic conditions, such as Behcet's syndrome, Reiter's disease, Sweet's syndrome, PFAPA syndrome, MAGIC syndrome, and HIV/AIDS infection, have been correlated to a higher frequency and severity of RAS disease [4; 5; 6; 8; 9; 10; 11].  
A recent study by [PERSON] et al. reported that a higher salivary expression of irisin, interleukin-2 (IL-2), and interferon-y (IF-y) was detected in the RAS group compared with the smoker and non-smoker cohort [12]. The authors supposed that a higher level of irisin could be involved with the mucosal healing process in the digestive system [12], and that this biomarker could be used for this purpose due to its high sensitivity for this disorder group.  
From the point of view of clinical treatment, several protocols have been proposed in the literature that are mainly symptomatic therapies that do not produce an elimination of the disease or do not influence its possible recrudescence in both adulthood and pediatric age [5; 6; 13; 14; 15; 16]. Although no curative treatments have been detected, several therapeutic approaches and active ingredients have been described including chlorhexiidine 0.2% in mouthwash, topical applications of benzidamine and zinc chloride, and polycresulene [6; 8; 9; 10; 11] devices. Possible therapeutic efficacy has been associated with tetracycline and lidocaine 1%, where many ulcerative lesions may sometimes recur and be refractory to such administrations [16; 17; 18].  
Regarding the efficacy of topical treatment, a clinical difficulty could be represented by the keeping the molecule in situ for a sufficient time to express its therapeutic action, in association with the dilution and wash-out effect of saliva [13; 18]. In addition, the bio-adhesiveness of soft tissues affected by aphthous lesions is a decisive factor for the effectiveness of treatment [19].  
The aim of the present research was to evaluate the efficacy of a gel formulation for a total treatment of 14 days for the treatment of oral ulcers of traumatic or aphthosic nature. The null hypothesis (H0) means that no difference at 14 days in the reduction in the mean pain sensation and ulcer area score, thermography [20; 21], and ulcer severity score (USS) [22] was detected between the two groups.