## 4 Discussion  
Results of this preliminary study suggest that the use of EDEBEX for ridge preservation surgeries allows for the formation of new bone tissue as early as two months after surgery, with an average of \(4.5\pm 2.6\) months. The amount of NFB found in the present study (NFB, \(43.2\pm 22.1\%\); RB, \(8.8\pm 5.9\%\)) is in line with another study that compared the histomorphometric outcome of particulate EDEB with anorganic bovine bone (ABB) used for post-extractive socket grafting [12]. In this latter study, NFB was observed to be significantly higher with EDEB than with ABB (\(45.12\pm 10.54\%\) vs. \(33.61\pm 9.71\%\)), and RB lower (\(10.91\pm 4.27\%\) vs. \(18.47\pm 5.62\%\)), with no difference in the healing time (\(4.1\pm 1.2\) vs. \(4.4\pm 1.2\) months) [12]. It is worth noting that the percentage of bioptic samples collected at an early stage of healing (\(<\)3.5 months) in the present study was almost double (\(53.85\%\) vs. \(27.27\%\)) compared to that reported in the study comparing EDEB and AB [12]. Altogether, these results suggest that the presence of type I bone collagen in its native conformation in EDEB, which is absent in ABB, allows for EDEB to undergo fast remodeling [12]. Indeed, the presence of type I collagen is known to be associated with active osteocl remodeling, as demonstrated by in vitro studies [26; 27]. A non-freeze-dried, mouldable version of EDEBEX combined with a demineralized bone matrix (DBM) was shown to stimulate the expression of known modulator of bone regeneration, such as the Runt-related transcription factor 2 (RUNX2), bone sialoprotein (BSP) and osteoclast in an in vitro study on human bone marrow stem cells [24]. The authors compared the results obtained with those achieved by EDEB + DBM mixed in a water-based carrier, showing that the latter did not exhibit such a pro-regenerative effect. This observation suggests that the Exur(r) carrier itself may contribute to the regenerative action of EDEBEX. The same study also investigated in vivo the effects of this bone paste when grafted in artificially induced femoral defects in rabbits. The histological analysis of the grafted sites at one and two months showed an interesting re-organization of the regenerating tissue within the lesion boundaries [24]. In one patient, this mouldable EDEBEX + DBM formulation, when grafted in post-extractive sockets, was observed to allow for considerable new bone formation already at three months from grafting (NFB, \(60.12\%\); RB = \(20.53\%\)) [28], a timing consistent with the observations reported in this study. Moreover, it can be also speculated that the pro-regenerative potential of EDEBEX may be partially due to the presence of ascorbic acid (vitamin C) in the hydrogel carrier, which may favor collagen deposition throughout the entire lesion volume. Indeed, ascorbic acid is known to  
Figure 5: Regression analysis between Marginal Bone Loss (MBL, mm) and Newly Formed Bone (NFB, %). be a co-factor for the activity of prolyl- and lysil-hydroxylases, essential enzymes for collagen fibril assembly [29]. From the operative perspective, the malleability of the EDEBEX bone paste granted by the hydrogel carrier ensures a more intimate contact between the graft and the underlying bone tissue, which can potentially favor bone regeneration. Even if a better performance of EDEBEX in terms of NFB was not observed when comparing the percentage obtained in the present study with that obtained in another study employing EDEB [12], it must be highlighted that the majority of the samples analyzed in the present study were collected after less than 3.5 months from the grafting surgery, suggesting a possible role of EDEBEX in further enhancing the regenerative performance showed by EDEB. The present study also highlights a satisfactory clinical outcome, with a good success rate (92.3%, only one implant failed) for implants placed in the grafted post-extractive sockets after an average of 4.5 months after grafting.