Surface Modification with Dopamine and Heparin/Poly-l-Lysine Nanoparticles Provides a Favorable Release Behavior for the Healing of Vascular Stent Lesions

Abstract

Surface biofunctional modification of coronary artery stents to prevent thrombosis and restenosis formation, as well as accelerate endothelialization, has become a new hot spot. However, bioactive coatings on implants are not yet sufficiently developed for long-term activity, as they quickly lose efficiency in vivo and finally fail. On the basis of a novel time-ordered concept of biofunctionality for vascular stents, heparin/poly l-lysine nanoparticle (NP) was developed and immobilized on a polydopamine-coated titanium surface, with the aim of regulating and maintaining the intravascular biological response within the normal range after biomaterial implantation. An in vitro dynamic release model was established to mimic the blood flow condition in vivo with three phases: (1) An early phase (1-7 days) with release of predominantly anticoagulant and anti-inflammatory substances and to a minor degree antiproliferative effects against smooth muscle cells (SMCs); (2) this is followed by a phase (7-14 days) of supported endothelial cell (ECs) proliferation and suppressed SMC proliferation with persisting high antithrombogenicity and anti-inflammatory properties of the surface. (3) Finally, a stable stage (14-28 days) with adequate biomolecules on the surface that maintain hemocompatibility and anti inflammation as well as inhibit SMCs proliferation and promote ECs growth. In vivo animal tests further confirmed that the NP-modified surface provides a favorable release behavior to apply a stage-adjusted remedy. We suggested that these observations provide important guidance and potential means for reasonable and suitable platform construction on a stent surface.

Cardiovascular stents: overview, evolution, and next generation

“…The formation of blood clot in the stent has been classified into two groups: (1) acute stent thrombosis (ST) due to inadequate stent expansion or arterial dissection occurs mostly within hours of the stent implantation, (2) sub-acute late ST which occurs up to 30 days after the implantation (Gandhi and Dawkins 1999 ). The first week is said to be the highest risk period for implantation (Liu et al 2014 ). To put the cascade biological events in order, the following 3-phase biological response is seen: (1) the inflammatory reaction occurs within 3–7 days, and the intimal thickness increases significantly in 4 weeks, (2) in the second phase, within 1–3 months, the stent surface is exposed to the blood flow within the vessel and the surrounding tissue starts to cover the stent surface.…”

Materials from Mussel-Inspired Chemistry for Cell and Tissue Engineering Applications

“…Furthermore, coated stents inhibited smooth muscle cell (SMC) proliferation and promoted endothelial cell growth without thrombus formation or intimal hyperplasia (Figure 5A). 123 Neural stem cells (NSCs) have shown excellent selfregenerative capacity toward neural cells, thereby offering a promising cell source to mitigate the issue of self-recovery of native neural-like cells and glial cells. 131,132 Pure NSCs suspended in culture medium frequently lack adequate physiochemical stimulation to initiate signaling cascades that promote proliferation and differentiation and often fail to survive post-transplantation.…”

Nanoparticles for Detection and Treatment of Peripheral Arterial Disease

“…The addition of NPs to BMS provides the inhibition of thrombosis and restenosis while promoting endothelialization. For instance, titanium vascular stents coated with polydopamine immobilized heparine/poly‐ l ‐lysisne NPs, supported endothelial regeneration, and prevented thrombus formation and neointimal hyperplasia in dog femoral arteries, when compared to arteries treated with a dopamine coated titanium stent (control) . In addition, stents coated with magnetic mesoporous silica nanoparticles (MMSNs) and carbon nanotubes (CNTs) have been explored .…”