# Angioplasty Using 4-Hexylresorcinol-Incorporated Silk Vascular Patch in Rat Carotid Defect Model
## 4 Discussion
Furthermore, according to the ultrasonography results, the velocity of blood flow in the control group significantly differed from that observed in the other groups (\(p\) < 0.05). This indicates that the diameter of artery was reduced, and that this reduction increased the blood flow velocity in the direct closure area. According to the results of the angiography, the blood flow velocities of the 4-HR silk and PTFE groups did not change after the angioplasty operation. This finding confirmed that the patch angioplasty can repair an arterial wall defect more effectively than the direct closure method. Furthermore, the efficacy of the 4-HR silk patch as a patch material was found to be comparable to that of the commercial PTFE patch product. Autogenous veins and xenogeneic and synthetic materials are used as vascular patch materials [50]. As a synthetic patch material, PTFE demonstrated acceptable suture strength and mechanical strength through its ability to resist blood pressure increase [51]. However, it carries the risk of inducing aforeign-body response that leads to chronic inflammation and thrombus formation [52]. The implanted synthetic biomaterial functions as a foreign body to the host, and control of this immune reaction is key to the success of the graft [53]. Foreign-body reaction and giant cell formation often occur around the implanted material, and can lead to graft failure and retrieval [53; 54]. Furthermore, although the PTFE material was successfully employed as a vascular patch in clinical applications, rare cases of infection and pseudoaneurysm after angioplasty were reported [9; 14]. In our experiment, severe aneurysm and granuloma formation were observed in the PTFE group. In contrast, in the 4-HR silk group, no signs of restenosis or an aneurysm were observed, and there was stable blood flow. Moreover, as previously reported, the 4-HR-incorporated silk cocoon demonstrated excellent biocompatibility as a vascular patch scaffold, and did not induce any severe immunological reaction [26]. The 4-HR compound has anti-microbial activity and is used as an antiseptic [55]. In consideration of these characteristics, in this study, 4-HR was used as a material component in the silk patch in order to prevent bacterial infection and an immune reaction, as this compound is known to inhibit foreign-body reaction and giant cell formation around the graft material area [31]. The 4-HR compound inhibits foreign-body giant cell formation via suppression of the diacylglycerol kinase in macrophages, and induces the biodegradation of the graft material [31; 34]. Thus, 4-HR is associated with soft-tissue healing and regeneration [56]. Furthermore, it inhibits tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)) expression in raw cells, and contributes to the rapid epithelization and collagen regeneration in burn wounds [56]. In our histological examination, we did not observe any inflammatory or immunological reaction in the 4-HR silk group. Instead, a newly regenerated endothelium was observed near the silk patch (Figure 7). The fluorescence and immunohistochemical examination results for the 4-HR silk group revealed a high level of vWF expression in the regenerated endothelium, and a well-maintained vascular lumen (Figures 8 and 9). In summary, 4-HR was not only demonstrated to be effective, but it was found to contribute to the success of the silk patch angioplasty by reducing the immune reaction and inducing endothelium regeneration. In a recent study, the proteins released from the silk mat of the silkworm cocoon were associated with an angiogenesis effect [57]. As previously mentioned, silk mat from the cocoon can be divided into layers of varying thickness by peeling the inner and outer layers [24]. Proteins released from the inner layer of the silk mat can induce expression of the angiogenesis-related gene [57].