## 4 Discussion  
In this study, a histological evaluation of tissue inflammation, bone formation, and the type of healing barrier adjacent to the scaffold was performed. Goats are a challenging experimental model, yet having lower premolars with two roots that often truncate as close as 2-4 mm from the cementoenamel junction makes it suitable to conduct in vivo studies to predict similar responses in human teeth. Thus, it was not surprising to notice epithelial proliferation and connective tissue in cases of inflamed fraction. Inflammation is a vital part of the immune system [26]; hence, it was used repeatedly in literature to monitor the healing process [27; 28]. Porous scaffolds seeded with bioactive substances have shown their ability to promote bone and dental regeneration where cells were able to migrate, grow, and differentiate [29]. Overall, our results showed similar slight inflammation in the scaffold samples which indicated a positive tissue response to each scaffold as found in preceding studies [30]. Moreover, bone formation was evident in all groups compared to the positive control group, which came in agreement with previous findings [31; 32]. No significant differences were detected between experimental groups at 1 month. The probable explanation for the high rate of repair is that the used scaffolds are biocompatible [11; 30] in addition to the SIM effect on angiogenesis and bone formation as shown in numerous experimental animal studies [33; 34; 35; 36]. At 3 months, CS scaffold showed significantly better performance compared to CL and CS/SIM groups. In addition, it was noticed clinically that the CS scaffold had better handling characteristics than CL as its structure permitted  
Figure 4: Histological section of fural perforation at 3 months repaired with (**A**) CollaCote showing less inflammation and more fibrosis (arrow). (**B**) Chitosan scaffold showing more bone formation and maturation (arrows), (**C**) Chitosan with Simvastatin scaffold showing dense fibroblastic tissue (*) and bone trabeculae with prominent reversal lines (arrows). H&E stain \(\times\) 40 magnification. Figure 3: Histological section of fural perforation at 1 month repaired with (**A**) CollaCote showing intense lymphocytic inflammatory infiltrate (arrow), (**B**) Chitosan scaffold showing inflammatory infiltrate with bone formation (arrows), (**C**) Chitosan with Simvastatin scaffold showing fibroblastic tissue (long arrows) with prominent vascularity (bv) and bone formation (short arrows). H&E stain \(\times\) 40 magnification. for a more controlled material packing into the furcation site. Previous studies reported the osteoclast and osteoblast's ability to regulate bone remodeling within the bone by balancing the amount of resorption and ossification which, therefore, is tightly linked to the number and activity of osteoclasts and osteoblast [37]. Continuous osteocl activity in CS/SIM subgroups was present and significantly shown by dense fibrobl tissue and bone trabeculae with prominent reversal lines at 3 months confirming the active bone formation. These results support previous studies where SIM reinforced bone formation [38; 39; 40]. Simvastatin showed its ability to trigger the early expression of growth factors, including vascular endothelial growth factor (VEGF) [41] and BMP-2, and to induce and accelerate the formation of bones locally [42]. The range of SIM doses is broad in the literature. Varied values have been investigated--2.2 mg [43; 44], 0.5 mg [33; 34], 0.1, 0.5, 1.0, and 1.5 mg [44]-- and shown positive or negative effects on bone repair. Since this study is a prolongation of our previous paper, we selected our fabricated CS with 0.05 mg SIM scaffold to continue with because it showed more osteoblastic differentiation among other examined concentrations [23]. Hence, different findings may be caused by varied local interactions or because SIM can be cytotoxic at certain doses--above 0.1 uM [45], 1 uM and 5 uM [41; 45], and higher than 0.5 uM [46].