## 4 Discussion
Carrying out an intergroup comparison between the last two abovementioned products, no differences for BoP were assessed at any time, except at T\({}_{3}\) for Biorepair Peribioma PRO when the index had further decreased. The benefit of the periodontal status obtained after using the three experimental toothpastes was directly linked to the properties of the ingredients contained inside. On the contrary, the absence of particular curative components in the control toothpaste (Meridol Gum Protection) justified the reduced benefit obtained with this product, which was limited to a slight reduction in BoP after baseline, with no influence on FMBS and mSBI. However,it is important to say that the clinical variations assessed cannot be connected only to the domociliary treatment alone but are mainly influenced by the in-office SRP. Specifically focusing on the favorable effects of the three experimental toothpastes on bleeding indexes, it is worth discussing their specific compositions to explain their action. All these experimental agents are composed of hyaluronic acid, which is a natural polysaccharide constituting the extracellular matrix of the connective tissue, and the use of which is widely recognized for the treatment of chronic periodontitis [15]. The use of this substance covers several medical areas, especially dermatology and plastic surgery; with regard to dentistry, and specifically periodonontology, hyaluronic acid has anti-inflammatory, regenerative, and anti-bacterial effects with potential in the treatment of periodontal disease. Because of its tissue healing properties, this compound is used as an adjunct to mechanical therapy in the treatment of periodontitis [16]. In addition to hyaluronic acid, the potential of using the three experimental toothpastes may also be linked to medicinal plant extracts (e.g., _Hamanelis virginiana_ Leaf Extract, _Spirulina platensis_ Extract, and Calendula Officials Flower Extract) that are common among the three pastes and whose action against anaerobic and facultative aerobic periodontal bacteria has been suggested in several studies [17; 18; 19]. In particular, the effect of _Calendula officinalis_ on oxidative stress and bone loss has been studied in rats subjected to experimental periodontitis, and a positive outcome was assessed for this substance with preservation of collagen fibers [20]. Considering _Spirulina platensis_ Extract, it is known to have an antimicrobial effect against _S. aureus, E. coli, P. aeruginosa, Klebsiella sp., Proteus_ sp., and _Embedobacter_ sp. ; a mass of evidence is in favor of Spirulina due to its anti-inflammatory effects [21]. Despite the general change in periodontal bleeding indexes assessed after the use of the three products in the respective groups, the effect size appeared to be the same only on mSBI, whereas the change generated on BoP and FMBS appeared to be different. For instance, Biorepair Plus Parodontgel and Biorepair Peribioma PRO showed the highest impact on BoP index, whereas Biorepair Gum Protection reported a lower effect, although more significant with respect to Meridol Gum Protection. In particular, the different result observed for Biorepair Plus Parodontgel and Biorepair Gum Protection can be ascribed to the presence of lactoferrin only in the former product. The anti-inflammatory action of this substance has widely been studied in in vitro periodontitis models as well as in observational clinical studies: in vitro lactoferrin exerts strong anti-inflammatory properties against gingival fibroblasts infected with _Precotella intermediia_, whereas in vivo the topical administration to patients suffering from periodontitis is able to decrease both the levels of cytokines in crevicular fluid (e.g., IL-6), as well as edema, bleeding, pocket depth, and gingival and plaque index, with a positive variation of clinical attachment levels [22].