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Restenosis and thrombosis formation after cardiovascular devices implantation continue to be problematic. Although various platforms and parameters of cardiovascular devices have been designed and optimized over the years, postoperative complications are hard to avoid. The native vascular endothelium always provide a nonthrombogenic surface as well as prevent intimal overproliferation, thereby, the presence of a confluent endothelial cell layer on material surfaces have been widely accepted as an ideal approach to improve the biocompatibility of implanted cardiovascular materials. Endothelialization on biomaterial surfaces is initially developed by in vitro cell seeding. However, numerous no-perfect parts of this method are existed for clinical use. The emergency of endothelial progenitor cells may provide a promising way for setting these limitations. Over the last decades, countless researches about EPCs-based in vivo induced self-endothelialization have been reported and mainly focused on cellular therapy, pharmacological therapy, materials designing, or surface biofunctional modification. This review details the development of endothelialization on cardiovascular material surfaces from in vitro to in vivo. Endothelialization progress on the basis of molecular biological level and bioinformatics theory is expected to be the key point in the coming decades.

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.

Nanozyme-based catalytic tumor therapyi sa n emerging therapeutic method with high reactivity in response to tumor microenvironments (TMEs). To overcome the current limitations of deficient catalytic activity of nanozymes,w e studied the contributing factors of enzymatic activity based on non-metallic-atom doping and irradiation. Nitrogen doping significantly enhanced the peroxidase activity of Ti-based nanozymes,whichwas shown experimentally and theoretically. Based on the excellent NIR-adsorption-induced surface plasmon resonance and photothermal effect, the enzymatic activity of TiNn anoparticles (NPs) was further improved under NIR laser irradiation. Hence,a na cidic TME-responsive and irradiation-mediated cascade nanocatalyst (TLGp) is presented by using TiN-NP-encapsulated liposomes linked with pHresponsive PEG-modified glucose oxidase (GOx). The integration of pH-responsive GOx-mediated H 2 O 2 self-supply, nitrogen-doping,a nd irradiation-enhanced enzymatic activity of TiNN Ps and mild-photothermal therapye nables an effective tumor inhibition by TLGp with minimal side effects in vivo.

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The endothelialization of the metal surface of vascular stents came into focus as a new method for improving the biocompatibility of intravascular stents. This article has its focus on building a biofunctional layer on the activated titanium surface with anti-CD34 antibody, vascular endothelial growth factor (VEGF), and heparin by a layer-by-layer (LBL) self-assembly technique, to promote the endothelialization of the surface. When compared with titanium surface, the number of adhered endothelial progenitor cells (EPCs) on LBLs increased 47.1% after 5 days culture, meanwhile the proliferation rate of EPCs on LBLs during 5 days culture also exhibit significantly improvement. The results of blood compatibility evaluation clearly show that the LBLs reduce the number of adhered and activated blood platelets (adhered: Ti 83% vs. LBL <20% and activated: Ti 57% vs. LBL 19%), and the activated partial thromboplastin time of the LBL surface prolonged about 20 s in compared with platelet-poor plasma. The assembled LBL thus improves the thromboresistance of the titanium surface. The presented biofunctional multilayer of anti-CD34, VEGF, and heparin on titanium can significantly improve the blood compatibility and the endothelialization of a medical device. The biofunctional layer supports generation of a new endothelium onto titanium surface by capturing EPCs and oriented differentiation.

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