Dual-functional surfaces of everolimus immobilised on biodegradable poly(l-lactic acid)/poly(d-lactic acid) scaffold mediated by polydopamine coating for stent development

Abstract

Drug-eluting stent (DES) is a promising treatment for atherosclerosis and in-stent restenosis. However, the long-term implantation of DES contributes to late-stent thrombosis due to the rapid release of anti-proliferative drug and delayed endotheliasation. Besides, the presence of anti-proliferative drugs which is typically effective in preventing in-stent restenosis, has also could suspend the healing process by inhibiting the growth of endothelial cells. Everolimus is one of the anti-proliferative drugs used in developing commercial DES. Therefore, this study, aimed at developing a dual-functional surfaces of everolimus immobilised polydopamine (PDA) on poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) scaffolds. The study, also printed scaffolds with different PLLA and PDLA compositions (100% PLLA, 0% PDLA; 90% PLLA, 10% PDLA; 80% PLLA, 20% PDLA and 70% PLLA, 30% PDLA) using three-dimensional (3D) printer. The study further subjected PLLA/PDLA scaffolds to wettability, mechanical and degradation analyses. The incorporation of PDLA into the blend of PLLA has increased the scaffold hydrophobicity and mechanical properties. Observation on the degraded PLLA/PDLA scaffolds show the capability in retaining its chemical functionalities. Less crack formation, less acidity of the degraded solution, higher percentages of remaining weight, greater average molecular weight and higher crystallinity percentages were recorded on the higher PDLA composition after the degradation analysis. The 80% PLLA and 20% PDLA scaffold blend was selected for further grafting and immobilisation processes due to its wettability, mechanical and degradation properties. The grafted scaffolds with the PDA intermediate layer were partly immobilised with different everolimus concentrations (0.01, 0.05 and 0.10 mM) to form dual-functional surfaces. The study further analyses the dual-functional surfaces of everolimus immobilised PDA using ATR-FTIR, XPS, SEM, AFM, wettability, everolimus quantification, drug release, coating stability, blood compatibility and in-vitro endothelial cell analyses. Immobilisation of the everolimus on the PDA layer through O–N and C–O covalent linkages was also determined. The flowery-structured everolimus demonstrated a lower wettability (103.33 ± 7.13°) and higher surface roughness (784.92 ± 21.33 nm) on the greater concentration of everolimus (0.10 mM). A sustainable drug release profile based on the zero-order release profile was acquired for 0.05 mM and 0.10 mM everolimus concentrations. The higher everolimus concentration produced greater contribution on the coating stability. All scaffolds were classified as non-haemolytic with haemolytic index less than 2%. The endothelial cells extensively proliferated on the PDA surface which support scaffold implantation in the abluminal area. Meanwhile, cell growth inhibition was observed on the everolimus surface. Thus, this dual-functional scaffolds are beneficial for DES application in preventing possible complications such as burst drug release, late-stent thrombosis and delayed endotheliasation.