Introduction: In-stent restenosis (ISR) is a serious problem after coronary stent implantation and remains a major concern with bare-metal stent [1]. The suitable surface properties of coronary stents for endothelial cell adhesion, migration and proliferation are important and desirable for surface modification of implanted biomaterials [2]. In this study, therefore, SiCOH plasma nanocoatings prepared by low-temperature plasma deposition were used for surface modification of 316L stainless steel (316L SS) stents to examine their effects on re-endothelialization under in vivo conditions.
Materials & Methods: 316L SS wafers (15 mm in diameter and 2 mm in thickness) and 316L SS stents (1.6 mm in diameter and 18 mm in length) used in this study. SiCOH plasma nanocoatings deposited under different TMS:O2 ratios were used to explore the best plasma conditions for treatment of intravascular 316L SS stents by performing in vitro platelet and human umbilical vein endothelial cell (HUVEC) adhesion test. With uncoated 316L SS stents as the control, the SiCOH plasma nanocoated 316L SS stents were implanted into rabbit abdominal artery model for in vivo evaluation of re-endothelialization and ISR inhibition.
Results & Discussion: SiCOH plasma nanocoatings with thickness of 30-40 nm were deposited by low-temperature plasmas from a gas mixture of trimethysilane (TMS) and oxygen at different TMS:O2 ratios. Water contact angle measurements showed that the SiCOH plasma nano-coating surfaces prepared from TMS:O2 = 1:4 are hydrophilic with contact angle of 29.5 ± 1.9°. The SiCOH plasma nanocoated 316L stainless steel (316L SS) wafers were first characterized by in vitro adhesion tests for blood platelets and HUVECs. the rational SiCOH plasma nanocoating sample can significantly decrease the amount of blood platelets adhering on surface. Compared with the cells on the 316L SS group, HUVECs spread better and exhibit much more pseudopodia on the SiCOH plasma nanocoatings groups. The in vitro test results showed that the SiCOH plasma nanocoatings prepared from TMS:O2 = 1:4 had excellent hemo- and cyto-compatibility. SEM showed that SiCOH plasma nanocoated stents were almost completely covered with cells after stent implantation for 1 week, in which the outline of implanted stent could be observed clearly. The surface of regenerative endothelium was compact and smooth without any hemocytes. The spindle-shaped ECs arrayed orderly, being paralleled to the flow direction. After 4 week implantation, obvious neointimal could be found on both bare 316L SS stents and SiCOH plasma nanocoatings groups. The difference between the two groups from SEM images showed that the outline of bare 316L SS stents was clearly seen with some cracks observed on the fragile neointimal, while the outline of SiCOH plasma nanocoatings groups was hardly to see, and the neointimal was healthy being similar to normal vessel wall. In conclusion, the SiCOH plasma nanocoatings applied to SiCOH plasma nanocoated 316L SS stents group were much more effective in preventing ISR than the uncoated bare 316L SS stents group. After implantation for 12 weeks, the animals testing results showed that the SiCOH plasma nanocoatings accelerated re-endothelialization and inhibited ISR with lumen reduction of 26.3 ± 10.1%, which were considerably less than the 41.9 ± 11.6% lumen reduction from the uncoated control group.
Conclusions: Low-temperature plasma deposition technology exhibits its capability in surface modification. The rational design of surface wettability depends on different demands and implanted sites. 12 weeks animal model results obtained in this study indicate that surface modification of 316L SS stents with appropriate SiCOH plasma nanocoatings could significantly accelerate re-endothelialization, effectively inhibit ISR, and show its great promise in clinical treatment of various cardiovascular diseases.
National Natural Science Foundation of China (11332003 and 30970721); National Key Technology R & D Program of China (2012BAI18B02); Fundamental Research Funds for the Central Universities (CQDXWL-2012-120, CQDXWL-2012-117, 2015CDJZR)
References:
[1] Saito T, Hokimoto S, Oshima S, et al. Metal allergic reaction in chronic refractory in-stent restenosis [J]. Cardiovasc Revasc Med, 2009, 10(1):17-22.
[2] Zhang Q, Shen Y, Tang C, et al. Surface modification of coronary stents with SiCOH plasma nanocoatings for improving endothelialization and anticoagulation [J]. J Biomed Mater Res B Appl Biomater, 2015, 103(2):464-472.