Re-endothelialization Process Research Articles

Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.

Efficacy and Safety Evaluation of Tacrolimus-Eluting Stent in a Porcine Coronary Artery Model.

A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests. Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC). The stent was then inserted into the porcine coronary artery and monitored for a duration of 4weeks. SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215nm revealed that the drug was continuously released over a period of 4weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES). Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.

Chitosan-salvianolic acid B coating on the surface of nickel-titanium alloy inhibits proliferation of smooth muscle cells and promote endothelialization.

Introduction: Intracranial stents are of paramount importance in managing cerebrovascular disorders. Nevertheless, the currently employed drug-eluting stents, although effective in decreasing in-stent restenosis, might impede the re-endothelialization process within blood vessels, potentially leading to prolonged thrombosis development and restenosis over time. Methods: This study aims to construct a multifunctional bioactive coating to enhance the biocompatibility of the stents. Salvianolic acid B (SALB), a bioactive compound extracted from Salvia miltiorrhiza, exhibits potential for improving cardiovascular health. We utilized dopamine as the base and adhered chitosan-coated SALB microspheres onto nickel-titanium alloy flat plates, resulting in a multifunctional drug coating. Results: By encapsulating SALB within chitosan, the release period of SALB was effectively prolonged, as evidenced by the in vitro drug release curve showing sustained release over 28days. The interaction between the drug coating and blood was examined through experiments on water contact angle, clotting time, and protein adsorption. Cellular experiments showed that the drug coating stimulates the proliferation, adhesion, and migration of human umbilical vein endothelial cells. Discussion: These findings indicate its potential to promote re-endothelialization. In addition, the bioactive coating effectively suppressed smooth muscle cells proliferation, adhesion, and migration, potentially reducing the occurrence of neointimal hyperplasia and restenosis. These findings emphasize the exceptional biocompatibility of the newly developed bioactive coating and demonstrate its potential clinical application as an innovative strategy to improve stent therapy efficacy. Thus, this coating holds great promise for the treatment of cerebrovascular disease.

Features of re-endothelialization process during implantation of coronary stents (review of literature)

Method of endovascular treatment for coronary artery lesions has made its way from balloon angioplasty to implantation of drug-eluting stents. Today, drug-eluting stents are widely used for coronary artery revascularization and have significantly reduced the incidence of restenosis compared to bare metal stents. Delayed or incomplete re-endothelialization is a very specific problem for most drug-eluting stents, as after their implantation, there is a risk of developing late thrombosis associated not only with incomplete endothelialization of the stent struts or impaired endothelial function, but also with chronic inflammatory reaction of the vascular wall. The development of stents with ultrathin struts, the abluminal coating of the struts with polymer and drug contribute to the decrease of vascular wall trauma and of the inflammatory response and provide faster stent endothelialization. Keywords: coronary heart disease, coronary stents, re-endothelialization, microporous coating, polymer-free antiproliferative coating, Yukon stent

One-step fabrication of self-healing poly(thioctic acid) coatings on ZE21B Mg alloys for enhancing corrosion resistance, anti-bacterial/oxidation, hemocompatibility and promoting re-endothelialization

Coating magnesium (Mg) alloy stents with biodegradable polymeric materials can address the problems of thrombosis, inflammation, and restenosis caused by poor corrosion resistance and delayed endothelialization; however, these commonly used polymer coatings and their degradation products have no therapeutic effect and sometimes bring extra-side effects. Herein, to develop a polymeric coating with an additional therapeutic effect from that of the polymer itself, a poly(thioctic acid)-based homopolymer was simply synthesized via solvent-free thermal polymerization (containing Zn2+ ions) of thioctic acid (TA), a bioactive ingredient originating from the human body. A Poly(TA-Zn) coating was fabricated on alkali-heat (Mg(OH)2) treated ZE21B alloys via a one-step method, followed by conjugating REDV peptides, to simultaneously enhance the corrosion resistance and re-endothelialization process. Surface characterization and performance were comprehensively investigated. Molecular dynamics (MD) simulations demonstrate that the Zn-O coordination bonds formed between Zn2+ ions and carboxylic groups can inhibit the depolymerization of the Poly(TA-Zn) polymer. SEM micrographs show that the Poly(TA-Zn) coating is homogeneous and has a thickness of 45.03 ± 4.85 μm, and this coating is sturdily bonded to the Mg(OH)2 modified ZE21B substrate. Electrochemical and immersion tests show that the Poly(TA-Zn) sample provides good corrosion protection for ZE21B substrates because of its excellent self-healing properties, and it exhibits superior anti-bacterial/oxidation properties. After immobilizing REDV peptides, Poly(TA-Zn)-REDV samples can substantially hinder platelet adhesion/activation, reduce hemolysis rate, selectively promote the proliferation of endothelial cells and inhibit the growth of smooth muscle cells, thereby improving the anti-coagulation and re-endothelialization ability of Mg substrates.

A review on developments of in-vitro and in-vivo evaluation of hybrid PCL-based natural polymers nanofibers scaffolds for vascular tissue engineering

The main objective of the present review article is to investigate the in-vitro and in-vivo biocompatibility behavior of hybrid PCL-based scaffolds with collagen, gelatin, and chitosan to improve endothelialization for VTE applications. It is reported that the high-rate failure of small diameters vascular grafts (SDVGs, <6 mm) due to adhesion of platelets and plasma protein and aggregation, over-proliferation of smooth muscle cells (SMCs), and neointimal hyperplasia at the implantation site is main challenge in vascular tissue engineering (VTE). The fast re-establishment of a functional endothelial cell (EC) layer representing a crucial importance strategy has been proposed to reduce these adverse outcomes. Polycaprolactone (PCL), with optimum mechanical properties, it showed great potential in biomedical applications, but its biocompatibility is still highly concerned in VTE. Modifications of the PCL vascular grafts by developing the hybrid structures using natural polymers with optimum hydrophilicity and biocompatibility properties in order to speed up the re-endothelialization process have been proposed over the last years. Analyzing the mentioned results in the present study can offer a better understanding of the benefits and challenges of applying the natural polymer as a thrombotic response upon implantation in clinical trials. Also, it can suggest the PCL-Collagen as the best framework for the fabrication of rationally designed SDVGs for VTE.

Exosome-eluting stents for vascular healing after ischaemic injury.

Drug-eluting stents implanted after ischaemic injury reduce the proliferation of endothelial cells and vascular smooth muscle cells and thus neointimal hyperplasia. However, the eluted drug also slows down the re-endothelialization process, delays arterial healing and can increase the risk of late restenosis. Here we show that stents releasing exosomes derived from mesenchymal stem cells in the presence of reactive oxygen species enhance vascular healing in rats with renal ischaemia-reperfusion injury, promoting endothelial cell tube formation and proliferation, and impairing the migration of smooth muscle cells. Compared with drug-eluting stents and bare-metal stents, the exosome-coated stents accelerated re-endothelialization and decreased in-stent restenosis 28 days after implantation. We also show that exosome-eluting stents implanted in the abdominal aorta of rats with unilateral hindlimb ischaemia regulated macrophage polarization, reduced local vascular and systemic inflammation, and promoted muscle tissue repair.

Endothelial progenitor cells as the target for cardiovascular disease prediction, personalized prevention, and treatments: progressing beyond the state-of-the-art.

Stimulated by the leading mortalities of cardiovascular diseases (CVDs), various types of cardiovascular biomaterials have been widely investigated in the past few decades. Although great therapeutic effects can be achieved by bare metal stents (BMS) and drug-eluting stents (DES) within months or years, the long-term complications such as late thrombosis and restenosis have limited their further applications. It is well accepted that rapid endothelialization is a promising approach to eliminate these complications. Convincing evidence has shown that endothelial progenitor cells (EPCs) could be mobilized into the damaged vascular sites systemically and achieve endothelial repair in situ, which significantly contributes to the re-endothelialization process. Therefore, how to effectively capture EPCs via specific molecules immobilized on biomaterials is an important point to achieve rapid endothelialization. Further, in the context of predictive, preventive, personalized medicine (PPPM), the abnormal number alteration of EPCs in circulating blood and certain inflammation responses can also serve as important indicators for predicting and preventing early cardiovascular disease. In this contribution, we mainly focused on the following sections: the definition and classification of EPCs, the mechanisms of EPCs in treating CVDs, the potential diagnostic role of EPCs in predicting CVDs, as well as the main strategies for cardiovascular biomaterials to capture EPCs.

Latest generation stents: is it time to revive the bioresorbable scaffold?

Bioresorbable scaffolds (BRS) have been introduced in the last decade in percutaneous coronary interventions. Despite several advantages being postulated, the negative results from the mid-term follow-up of the Absorb trials have tempered enthusiasm for these innovative devices. The Absorb scaffold was associated with higher rates of target-lesion failure and scaffold thrombosis when compared to current metallic stents, and for this reason was withdrawn from the market. This failure has to be considered multifactorial, involving technical and technological aspects. Continuous engineering refinements in BRS technology, means newer-generation devices are available in clinical practice, and several more are under preclinical and clinical assessment. Thinner and smaller struts, associated with a faster resorption and reendothelialization process, are at the basis of promising preclinical results for new BRS. In this review we summarize the Absorb scaffold experience and focus on the latest evidence concerning emerging new BRS, to explore if a "BRS revival" is conceivable.

Collagen-Based Tissue Engineering Strategies for Vascular Medicine.

Cardiovascular diseases (CVDs) account for the 31% of total death per year, making them the first cause of death in the world. Atherosclerosis is at the root of the most life-threatening CVDs. Vascular bypass/replacement surgery is the primary therapy for patients with atherosclerosis. The use of polymeric grafts for this application is still burdened by high-rate failure, mostly caused by thrombosis and neointima hyperplasia at the implantation site. As a solution for these problems, the fast re-establishment of a functional endothelial cell (EC) layer has been proposed, representing a strategy of crucial importance to reduce these adverse outcomes. Implant modifications using molecules and growth factors with the aim of speeding up the re-endothelialization process has been proposed over the last years. Collagen, by virtue of several favorable properties, has been widely studied for its application in vascular graft enrichment, mainly as a coating for vascular graft luminal surface and as a drug delivery system for the release of pro-endothelialization factors. Collagen coatings provide receptor–ligand binding sites for ECs on the graft surface and, at the same time, act as biological sealants, effectively reducing graft porosity. The development of collagen-based drug delivery systems, in which small-molecule and protein-based drugs are immobilized within a collagen scaffold in order to control their release for biomedical applications, has been widely explored. These systems help in protecting the biological activity of the loaded molecules while slowing their diffusion from collagen scaffolds, providing optimal effects on the targeted vascular cells. Moreover, collagen-based vascular tissue engineering substitutes, despite not showing yet optimal mechanical properties for their use in the therapy, have shown a high potential as physiologically relevant models for the study of cardiovascular therapeutic drugs and diseases. In this review, the current state of the art about the use of collagen-based strategies, mainly as a coating material for the functionalization of vascular graft luminal surface, as a drug delivery system for the release of pro-endothelialization factors, and as physiologically relevant in vitro vascular models, and the future trend in this field of research will be presented and discussed.

Heparin-Modified Collagen Gels for Controlled Release of Pleiotrophin: Potential for Vascular Applications.

A fast re-endothelialization, along with the inhibition of neointima hyperplasia, are crucial to reduce the failure of vascular bypass grafts. Implants modifications with molecules capable of speeding up the re-endothelialization process have been proposed over the last years. However, clinical trials of angiogenic factor delivery have been mostly disappointing, underscoring the need to investigate a wider array of angiogenic factors. In this work, a drug release system based on a type I collagen hydrogel has been proposed for the controlled release of Pleiotrophin (PTN), a cytokine known for its pro-angiogenetic effects. Heparin, in virtue of its ability to sequester, protect and release growth factors, has been used to better control the release of PTN. Performances of the PTN drug delivery system on endothelial (ECs) and smooth muscle cells (SMCs) have been investigated. Structural characterization (mechanical tests and immunofluorescent analyses of the collagen fibers) was performed on the gels to assess if heparin caused changes in their mechanical behavior. The release of PTN from the different gel formulations has been analyzed using a PTN-specific ELISA assay. Cell viability was evaluated with the Alamar Blue Cell Viability Assay on cells directly seeded on the gels (direct test) and on cells incubated with supernatant, containing the released PTN, obtained from the gels (indirect test). The effects of the different gels on the migration of both ECs and SMCs have been evaluated using a Transwell migration assay. Hemocompatibility of the gel has been assessed with a clotting/hemolysis test. Structural analyses showed that heparin did not change the structural behavior of the collagen gels. ELISA quantification demonstrated that heparin induced a constant release of PTN over time compared to other conditions. Both direct and indirect viability assays showed an increase in ECs viability while no effects were noted on SMCs. Cell migration results evidenced that the heparin/PTN-modified gels significantly increased ECs migration and decreased the SMCs one. Finally, heparin significantly increased the hemocompatibility of the collagen gels. In conclusion, the PTN-heparin-modified collagen here proposed can represent an added value for vascular medicine, able to ameliorate the biological performance, and integration of vascular grafts.

Noninvasive in vivo Assessment of the Re-endothelialization Process Using Ultrasound Biomicroscopy in the Rat Carotid Artery Balloon Injury Model.

Ultrasound biomicroscopy (UBM), or ultra high-frequency ultrasound, is a technique used to assess the anatomy of small research animals. In this study, UBM was used to assess differences in intimal hyperplasia thickness as a surrogate measurement of the re-endothelialization process after carotid artery balloon injury in rats. Ultrasound biomicroscopic data from 3 different experiments and rat strains (Sprague Dawley, Wistar, and diabetic Goto-Kakizaki) were analyzed. All animals were subjected to carotid artery balloon injury and examined with UBM (30-70 MHz) 2 and 4 weeks after injury. Re-endothelialization on UBM was defined as the length from the carotid bifurcation to the most distal visible edge of the intimal hyperplasia. En face staining with Evans blue dye was performed at euthanasia 4 weeks after injury, followed by tissue harvesting for histochemical and immunohistochemical evaluations. A significant correlation (Spearman r = 0.63; P < .0001) was identified when comparing all measurements of re-endothelialization obtained from UBM and en face staining. The findings revealed a similar pattern for all rat strains: Sprague Dawley (Spearman r = 0.70; P < .0001), Wistar (Spearman r = 0.36; P < .081), and Goto-Kakizaki (Spearman r = 0.70; P < .05). A Bland-Altman test showed agreement between en face staining and UBM. Immunohistochemical staining confirmed the presence of the endothelium in the areas detected as re-endothelialized by the UBM assessment. Ultrasound biomicroscopy can be used for repeated in vivo assessment of re-endothelialization after carotid artery balloon injury in rats.

Abstract 245: Non-Invasive in vivo Assessment of the Re-Endothelialization Process Using Ultrasound Biomicroscopy in the Rat Carotid Artery Balloon Injury Model

Objective: Ultrasound BioMicroscopy (UBM), or high-frequency ultrasound, is a novel technique used for assessment of anatomy and physiology small research animals. In this study, we evaluate the UBM assessment of the re-endothelialization process following denudation of the carotid artery in rats. Methods: Ultrasound BioMicroscopy data from three different experiments were analyzed. A total of 66 rats of three different strains (Sprague-Dawley, Wistar and Goto-Kakizaki) were included in this study. All animals were subjected to common carotid artery balloon injury and examined with UBM 2 and 4 weeks after injury. Re-endothelialization in UBM was measured as the length from the carotid bifurcation to the distal edge of the intimal hyperplasia. En face staining with Evans-blue dye was performed upon euthanization at 4 weeks after injury followed by tissue harvest for morphological and immunohistochemical evaluation. Results: A significant correlation (Spearman r=0.63,p&lt;0.0001) and an agreement according to Bland-Altman test was identified when comparing all measurements of re-endothelialization in high frequency ultrasound and en face staining. Analysis by animal strain revealed a similar pattern and a significant growth in re-endothelialization length measured in UBM from 2 to 4 weeks could be identified. Immunohistochemical staining for von Willebrand factor confirmed the presence of endothelium in the areas detected as re-endothelialized by the ultrasound assessment. Conclusion: Ultrasound BioMicroscopy can be used for longitudinal in vivo assessment of the re-endothelialization following arterial injury in rats.

Magnetically enhanced cell delivery for accelerating recovery of the endothelium in injured arteries

Arterial injury and disruption of the endothelial layer are an inevitable consequence of interventional procedures used for treating obstructive vascular disease. The slow and often incomplete endothelium regrowth after injury is the primary cause of serious short- and long-term complications, including thrombosis, restenosis and neoatherosclerosis. Rapid endothelium restoration has the potential to prevent these sequelae, providing a rationale for developing strategies aimed at accelerating the reendothelialization process. The present studies focused on magnetically guided delivery of endothelial cells (EC) functionalized with biodegradable magnetic nanoparticles (MNP) as an experimental approach for achieving rapid and stable cell homing and expansion in stented arteries. EC laden with polylactide-based MNP exhibited strong magnetic responsiveness, capacity for cryopreservation and rapid expansion, and the ability to disintegrate internalized MNP in both proliferating and contact-inhibited states. Intracellular decomposition of BODIPY558/568-labeled MNP monitored non-invasively based on assembly state-dependent changes in the emission spectrum demonstrated cell proliferation rate-dependent kinetics (average disassembly rates: 6.6±0.8% and 3.6±0.4% per day in dividing and contact-inhibited EC, respectively). With magnetic guidance using a transient exposure to a uniform 1-kOe field, stable localization and subsequent propagation of MNP-functionalized EC, markedly enhanced in comparison to non-magnetic delivery conditions, were observed in stented rat carotid arteries. In conclusion, magnetically guided delivery is a promising experimental strategy for accelerating endothelial cell repopulation of stented blood vessels after angioplasty.

Abstract 476: Glucagon Like Peptide -1 Receptor Activation Does Not Affect Re-endothelialization But Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Non-diabetic Model of Arterial Injury

Background/Aims: Diabetic patients have an increased risk of restenosis and late stent thrombosis after angioplasty, complications that are related to a defective re-endothelialization. Exendin-4, a stable GLP-1 receptor agonist has been suggested to influence the formation of intimal hyperplasia and to increase endothelial cell proliferation in vitro. Thus, the aim of the study was to investigate the mechanisms by which treatment with exendin-4 could influence re-endothelialization and intimal hyperplasia after vascular injury. Methods: 40 male Sprague-Dawley rats were subjected to balloon injury of the left common carotid artery (LCCA) and treated for four weeks with exendin-4 (1 nmol/day) or vehicle. Intimal hyperplasia and vessel wall elasticity were monitored non-invasively by high frequency ultrasound and re-endothelialization was evaluated upon sacrifice using Evans blue dye. The LCCA was then sectioned for subsequent morphometric and immunohistochemical analyses. To further investigate if and how smooth muscle cells (SMCs) are directly affected by exendin-4 treatment, we studied proliferation and apoptosis of SMCs in vitro. Results and Conclusion: Exendin-4 selectively reduced proliferation of SMCs and intimal hyperplasia in vivo without affecting the re-endothelialization process, however treatment with exendin-4 improved arterial wall elasticity. Our data also show that exendin-4 significantly decreased the proliferation and increased the apoptosis of SMCs in vitro, effects that appear to be mediated through cAMP signaling and endothelial nitric oxide synthase following GLP-1 receptor activation. Together, these effects of exendin-4 are highly desirable and may lead to improved outcome for patients undergoing vascular interventions.

MiR-92a – a key player in cardiovascular remodeling

Small non-coding, highly conserved microRNAs (miRs) play a crucial role in gene regulation, especially in post-transcriptional gene silencing, and are important for vascular homeostasis as well as during pathophysiological vascular remodeling processes. MiR-92a is known to attenuate endothelial cell proliferation, and angiogenesis. Conversely, down regulation of miR-92a improves these endothelial cell-dependent processes. We recently showed that inhibition of miR-92a also accelerates the re-endothelialization process and thus prevents neointima formation following wire-induced injury of murine femoral arteries. Thus, inhibition of miR-92a may represent a promising therapeutic strategy for the treatment of vascular diseases.

Glucagon-Like Peptide-1 Receptor Activation Does Not Affect Re-Endothelialization but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Nondiabetic Model of Arterial Injury

Diabetic patients have an increased risk of restenosis and late stent thrombosis after angioplasty, i.e. complications that are related to a defective re-endothelialization. Exendin-4, a stable glucagon-like peptide (GLP)-1 receptor agonist, has been suggested to influence the formation of intimal hyperplasia and to increase endothelial cell proliferation in vitro. Thus, the aim of this study was to investigate the mechanisms by which treatment with exendin-4 could influence re-endothelialization and intimal hyperplasia after vascular injury. Methods: Sprague-Dawley rats were subjected to balloon injury of the left common carotid artery and treated for 4 weeks with exendin-4 or vehicle. Intimal hyperplasia and vessel wall elasticity were monitored noninvasively by high-frequency ultrasound, and re-endothelialization was evaluated upon sacrifice using Evans blue dye. Results and Conclusion: Exendin-4 selectively reduced the proliferation of smooth muscle cells (SMCs) and intimal hyperplasia in vivo without affecting the re-endothelialization process, but treatment with exendin-4 improved arterial wall elasticity. Our data also show that exendin-4 significantly decreased the proliferation and increased the apoptosis of SMCs in vitro, effects that appear to be mediated through cAMP signaling and endothelial nitric oxide synthase following GLP-1 receptor activation. Together, these effects of exendin-4 are highly desirable and may lead to an improved outcome for patients undergoing vascular interventions.

Neutrophils as new conductors of vascular homeostasis

Endothelial progenitor cells (EPCs) and stem cells have therapeutic potential for the treatment of peripheral arterial disease (PAD) and acute coronary syndrome (ACS) 1. These cells are thought to act either by giving rise to new vessels in situ or as helper cells to mature endothelial cells during the reendothelialization process after vascular injury. Within the context of thrombosis, different EPC subtypes can be recruited to sites of vessel damage, and, depending on the model used, they have been shown either to be beneficial for thrombus resolution or, conversely, to exhibit deleterious thrombotic effects.

Fabrication of a Novel Polymer-Free Nanostructured Drug-Eluting Coating for Cardiovascular Stents

Angioplasty with stents is the most important method for the treatment of coronary artery disease (CAD). However, the drug-eluting stents (DES) that are widely used have the increased risks of inflammatory reactions and late stent thrombosis (LST) because of the persistence of the polymer coatings. To improve the biosafety, a novel polymer-free-composite drug-eluting coating composed of magnetic mesoporous silica nanoparticles (MMSNs) and carbon nanotubes (CNTs) was constructed using the electrophoretic deposition (EPD) method in this study. A crack-free two-layered coating with impressive network nanotopologies was successfully obtained by regulating the composition and structures. This nanostructured coating exhibits excellent mechanical flexibility and blood compatibility in vitro, and the drug-loading and release performance is satisfactory as well. The in vivo study shows that this composite coating has the obvious advantage of rapid endothelialization because of its unique 3D nanostructured topology in comparison with the commercial polymer-coated DES. This study aims to provide new ideas and reliable data to design novel functional coatings that could accelerate the re-endothelialization process and avoid inflammatory reactions, thus improving the in vivo biosafety of DES.

Site‐selective immobilization of anti‐CD34 antibodies to poly(l‐lactide) for endovascular implant surfaces

Aiming at a speed up of the re-endothelialization process of biodegradable endovascular implants, novel approaches for the functionalization of poly(l-lactide) (PLLA) with anti-CD34 antibodies were established. We propose a three-step process involving PLLA surface activation with functional amino groups, attachment of a protein repelling peptide spacer, and covalent random or site-selective immobilization of the antibodies. Obtainable antibody surface densities and antigen binding capacities were thoroughly evaluated by means of enzyme-linked immunosorbent assay. Results indicate that a lower amount of anchoring sites on the antibody favors high coupling efficiency, while localization of the anchoring sites, facing the antigen binding moiety, strongly enhances the antigen capture capacity of the support. Besides minimization of physisorption and cell adhesion exemplarily shown with bovine serum albumin, avidin, and human umbilical vein endothelial cells, respectively, the inclusion of the protein-repelling spacer strengthened this effect, yielding antigen capture capacities exceeding values so far reported in literature. In contrast, the number of amino groups on the PLLA surfaces, which is indeed highly dependent on the applied activation procedure, does not seem to influence antibody coupling efficiency and antigen capture capacity considerably. This allows the choice of surface activation treatment, plasma or wet-chemical, regarding other processing parameters as for instance sterilizability or favored modification depth.