In situ endothelialization of intravascular stents from progenitor stem cells coated with nanocomposite and functionalized biomolecules

Abstract

Abstract.Owing to their noninvasive nature, coronary artery stents have become popular demand for patients undergoing percutaneous coronary intervention. Late restenosis, in-stent restenosis, and late thrombosis, all mediated by the denuded endothelium, represent the most recurrent failures of vascular stent induction. Higher patency rates of stents can be achieved by restoring the native internal environment of the vessel-an endothelium monolayer. This active organ inhibits the inflammatory reaction to injury responsible for thrombus and intimal hyperplasia, thereby providing a novel therapeutic option to combat the unacceptably high prevalence of restenosis. As the climax of the nanotechnology era approaches, tissue engineering is being explored by means of exploiting the multipotent abilities of stem cells and their adherence to bioactive surface nanocomposite polymers. The endothelium can be reconstructed from neighboring intact endothelium and adherence of circulating endothelium progenitor cells. The latter takes place via a series of signaling events: mobilization, adhesion, chemoattraction, migration, proliferation, and finally their differentiation in mature endothelial cells. A nanotopography surface can orchestrate endothelium formation, attributable to cellular interactions promoted by its nanosize. This review encompasses the prospect of in situ endothelialization, the mechanisms regulating the process, and the advantages of using a new generation of bioactive nanocomposite materials for coating metal stent scaffolds.

A Nanocage for Nanomedicine: Polyhedral Oligomeric Silsesquioxane (POSS)

“…To meet the essential requirements for these applications, we have developed nanocomposite materials by copolymerization of POSS monomers with poly(carbonate urea)urethane (POSS-PCU) to form covalently modified and cross-linked nanostructures within the hard segments, and form pendant chain groups. [10,[50][51][52][53] Studies on its cytocompatibility, anti-thrombogenicity, and biostability have shown that this nanocomposite polymer has unique characteristics for applications at the blood-biomaterial interface. [52] This nanocomposite polymer can be biofunctionalized by anchoring peptides and growth factors through surface modification in order to attract endothelial progenitor cells (EPCs) from the circulatory blood, and become endothelialized to enhance the bio-and haemocompatibility of cardiovascular devices made with this material ( Figure 2).…”

Intracranial Stents Past, Present and the Future Trend: Stents Made with Nano-particle or Nanocomposite Biomaterials

“…Theoretically, rapid endothelialization of the luminal surfaces of stents is a way of increasaing implant patency and preventing in-stent stenosis by inhibiting both thrombosis and intimal hyperplasia [39]. Recent studies focus on the immobilization of endothelial progenitor cell (EPC) specific antibodies for circulating EPC capturing [40]. Many in vitro and in vivo studies have already successfully induced EPC incorporation onto target sites, and the immobilized EPCs have been observed to be differentiated and proliferated into an EC monolayer [41].…”

“…It does not cause inflammatory reactions in the surrounding host tissue [46][47][48][49]. Experiments in cardiac implants also prove that POSS-PCU has a fine quality of calcification resistance (Alobaid et al, 2006;Motwani et al, 2011). POSS-PCU has already been used first-in-human studies as a bypass graft [50], lacrimal duct [51] and the world's first synthetic trachea [52,53].…”

In Vitro Studies of Polyhedral Oligo Silsesquioxanes: Evidence for Their Low Cytotoxicity

“…Studies on polyhedral oligo silsesquioxanes (POSS) were limited to conjugation with fluorescent dyes [5], incorporation into dendrimeric systems [6,7], development of dental nano-composites [8] and cardiovascular implants [9]. Silsesquioxanes were scarcely studied as drug delivery systems and never as moieties covalently conjugated with drugs, even though they are free of the disadvantages of polymers as polydispersity of hyperbranched polymers or laborious syntheses of dendrimers.…”