Figure 5-6 h & E staining section of selected segments at the following time points
(a) 1 month, (b) 3 months, (c) 9 months and (d) 24 months; (A1), (B1) and (C1) are partially enlarged images of (a), (b) and (c), respectively; (D1), (D2) and (D3) are partially enlarged images of (d); (D1) the green square marks the previous position of the strut and has been replaced by smooth muscle cells. (D2) the image obtained by overexposure clearly shows the pillar residues and corrosion products (marked with black arrows); (D3) white arrow marks epithelioid cells, green arrow marks lymphocytes, green circle highlights foreign body macrophages, and the size of corrosion products is 10 ~ 15 μ m
In early studies, it was found that iron-based implants produced layered corrosion products 9 months after implantation of blood vessels, and pushed the surrounding biological tissue > 750 away from the surface of the original implant μ m. There is little organizational integration [33]. In Figure 5-6, the zinc copper alloy scaffold rod residues and corrosion products are closely surrounded by tissues throughout the study cycle, which shows that the zinc copper alloy scaffold has good histocompatibility.
Figures 5-6 (a) and 5-6 (A1) show that the endothelialization process can be completed within the first month after operation, which well confirms the results observed by Oct. Rapid endothelialization is one of the important conditions for good after stent implantation. The endothelialization rate of zinc copper stent can meet the clinical needs.
Three months after the implantation of Zn Cu scaffold, epithelial like macrophages with deeply stained nuclei (Fig. 5-6 (b) and Fig. 5-6 (B1)) can be seen gathered around the scaffold rod. This is a common lymphocyte in the process of foreign body inflammation, which is transformed by macrophages phagocytizing some indigestible bacteria or long-term stimulation of other antigenic substances [34]. It shows that zinc and its primary and secondary metabolites exist in the vascular wall as foreign bodies, which continuously stimulates the body to produce a relatively stable foreign body inflammatory reaction. After 9 months of implantation, macrophage infiltration decreased and changed to mild inflammation (Fig. 5-6 (c) and Fig. 5-6 (C1)). Throughout the observation period, the inflammatory response of zinc copper stent in this study was similar to that of pure zinc stent in rabbit model [35]. In this study, no new risks related to stent vessels caused by copper addition were found.
Fig. 5-6 (d) shows a partially degraded scaffold rod, which has been replaced by cells similar to natural smooth muscle cells (SMC). The area marked by the green square in Figure 5-6 (D1) is the previous position of the partially degraded support rod, which has been replaced by SMC, and there is no serious inflammatory reaction. The black deeply stained corrosion products were observed near the original support rod, and the diffusion direction of the corrosion products was opposite to the center of the lumen. Figure 5-6 (D2) is a light microscopic photograph obtained by excessive exposure, in which the black arrow marks the degradation product of the strut. Figure 5-6 (D2) shows that after the degradation product is formed around the support rod, it can be decomposed into small product debris (< 20) μ m) And diffuse to the outer membrane (reverse to the vascular lumen), rather than not staying in situ or agglomerating into large-size agglomerates that are not easy to diffuse and further degrade.
There are two possibilities for outward migration of corrosion products. One is through body fluid in the intercellular pathway, and the other is through cell phagocytosis in the cellular pathway. The green circle in Figure 5-6 (D3) marks a piece of corrosion product and the cells that swallow the corrosion product. There are more than 10 nuclei scattered around the corrosion products, which is the morphological feature of foreign giant cells. Foreign body type giant cells are formed by epithelioid macrophages stimulated by chemokines, gathered around zinc and its degradation products, and further combined. Figure 5-6 (D3) shows that the formed multinuclear foreign body giant cells phagocytized the degradation product fragments of zinc copper scaffolds and transported towards the outer membrane. This is the direct evidence that the degradation products of zinc copper scaffolds migrate to the outer membrane through the cellular pathway, suggesting that the degradation products of zinc copper scaffolds may complete the final metabolism through the human body's foreign body removal system. The transfer of the product to the outer membrane ensures that in this process, the stent rod will be replaced by normal tissue without the risk of entering the blood circulation system and causing thrombosis or inflammatory reaction. During the study period, the neointima observed by OCT was smooth, no thrombosis or serious inflammatory reaction was found, which also confirmed that the transport of corrosion products of zinc copper stent in the stent model was safe.
