Enhanced biocompatibility of CD47-functionalized vascular stents

Abstract

The effectiveness of endovascular stents is hindered by in-stent restenosis (ISR), a secondary re-obstruction of treated arteries due to unresolved inflammation and activation of smooth muscle cells in the arterial wall. We previously demonstrated that immobilized CD47, a ubiquitously expressed transmembrane protein with an established role in immune evasion, can confer biocompatibility when appended to polymeric surfaces. In present studies, we test the hypothesis that CD47 immobilized onto metallic surfaces of stents can effectively inhibit the inflammatory response thus mitigating ISR. Recombinant CD47 (recCD47) or a peptide sequence corresponding to the Ig domain of CD47 (pepCD47), were attached to the surfaces of both 316L-grade stainless steel foils and stents using bisphosphonate coordination chemistry and thiol-based conjugation reactions to assess the anti-inflammatory properties of CD47-functionalized surfaces. Initial in vitro and ex vivo analysis demonstrated that both recCD47 and pepCD47 significantly reduced inflammatory cell attachment to steel surfaces without impeding on endothelial cell retention and expansion. Using a rat carotid stent model, we showed that pepCD47-functionalized stents prevented fibrin and platelet thrombus deposition, inhibited inflammatory cell attachment, and reduced restenosis by 30%. It is concluded that CD47-modified stent surfaces mitigate platelet and inflammatory cell attachment, thereby disrupting ISR pathophysiology.

GalT‐KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels

“…Our data, along with previous data in vitro and in vivo, are consistent with the hypothesis that species incompatibility of CD47 and its ligand, SIRPα, may play an important role in the early destruction of endothelium in the alveolar network, resulting in hemorrhagic changes in lung grafts. In the present study, the lung grafts of both recipients surviving >7 days expressed hCD47 not only on alveolar epithelium but also on the endothelium, while all other lungs lacked hCD47 expression on the endothelium, despite the expression of hCD47 in alveoli.…”

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

“…For the second generation of DESs, whose coatings mostly delivered paclitaxel and sirolimus together with their analogues 43 , the coating could only achieve short-term anti-proliferative function with delayed re-endothelialization. Most vascular stent coatings that have been produced have been given only one kind of function, such as the inhibition of inflammation 44,45 , promotion of re-endothelialization 46 or a novel way of preventing in-stent restenosis 47 . In our design, we arranged the coating to have dual anti-thrombosis and anti-restenosis functions.…”

Paraffin processing of stented arteries using a postfixation dissolution of metallic and polymeric stents

“…After performing carotid balloon denudation with 3 passages of a 2F Fogarty catheter (Edwards LifeSciences, Irvine, CA) the stents (n=5 for each stent type) were deployed with PTA catheters (1.5 mm nominal diameter; NuMed) at 16 atm in the mid-segments of the left common carotid arteries as described in our previous publications [12–14]. The animals were euthanized 14 days after stent deployment.…”