Bioclickable and mussel adhesive peptide mimics for engineering vascular stent surfaces.

Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.

[Effects of Heat Treatment Conditions on Shape Memory Recovery of NiTi Self-expanding Vascular Stents].

Effects of heat treatment conditions (including temperature and time) on the shape memory recovery and corrosion resistance of NiTi self-expanding vascular stents were studied based on working mechanism and clinical use. The Af temperature, dimensional recovery, crush resistance with radially applied load and point applied load of stents and corrosion resistance were characterized in diffident heat treatment conditions. The research results allow the conclusion that the stent treated at 500 ℃ for 10 min has optimum performance, and corrosion resistance meets the requirements.

Pharmacologic targeting of coagulation factors XII and XI by monoclonal antibodies reduces thrombosis in nitinol stents under flow.

BACKGROUND: Cardiovascular implantable devices, such as vascular stents, are critical for the treatment of cardiovascular diseases. However, their success is dependent on robust and often long-term antithrombotic therapies. Yet, the current standard-of-care therapies often pose significant bleeding risks to patients. Coagulation factor (F)XI and FXII have emerged as potentially safe and efficacious targets to safely reduce pathologic thrombin generation in medical devices. OBJECTIVES: To study the efficacy of monoclonal antibody-targeting FXII and FXI of the contact pathway in preventing vascular device-related thrombosis. METHODS: The effects of inhibition of FXII and FXI using function-blocking monoclonal antibodies were examined in a nonhuman primate model of nitinol stent-related thrombosis under arterial and venous flow conditions. RESULTS: We found that function-blocking antibodies of FXII and FXI reduced markers of stent-induced thrombosis in vitro and ex vivo. However, FXI inhibition resulted in more effective mitigation of thrombosis markers under varied flow conditions. CONCLUSION: This work provides further support for the translation of contact pathway of coagulation inhibitors for their adjunctive clinical use with cardiovascular devices.

Methods for improving the properties of zinc for the application of biodegradable vascular stents.

Biodegradable stents can support vessels for an extended period, maintain vascular patency, and progressively degrade once vascular remodeling is completed, thereby reducing the constraints of traditional metal stents. An ideal degradable stent must have good mechanical properties, degradation behavior, and biocompatibility. Zinc has become a new type of biodegradable metal after magnesium and iron, owing to its suitable degradation rate and good biocompatibility. However, zinc's poor strength and ductility make it unsuitable as a vascular stent material. Therefore, this paper reviewed the primary methods for improving the overall properties of zinc. By discussing the mechanical properties, degradation behavior, and biocompatibility of various improvement strategies, we found that alloying is the most common, simple, and effective method to improve mechanical properties. Deformation processing can further improve the mechanical properties by changing the microstructures of zinc alloys. Surface modification is an important means to improve the biological activity, blood compatibility and corrosion resistance of zinc alloys. Meanwhile, structural design can not only improve the mechanical properties of the vascular stents, but also endow the stents with special properties such as negative Poisson 's ratio. Manufacturing zinc alloys with excellent degradation properties, improved mechanical properties and strong biocompatibility and exploring their mechanism of interaction with the human body remain areas for future research.

Mechanical analysis of radial performance in biodegradable polymeric vascular stents manufactured using micro-injection molding.

Micro-injection molding (MiM) is a promising technique for manufacturing biodegradable polymeric vascular stents (BPVSs) at scale, in which a trapezoidal strut cross section is needed to ensure high-quality de-molding. However, there is a lack of research on the influence of the strut cross-sectional shape on its mechanical properties, posing a challenge in determining the key geometries of the strut when using MiM to produce BPVSs. Hence, this work has investigated the relationships between the geometry parameters, including the de-molding angle, and the radial support property of BPVSs using the finite element method. The results reveal that the radial stiffness of BPVSs is significantly affected by the de-molding angle, which can be counteracted by adjusting strut height, bending radius, and strut thickness. Stress distribution analysis underscores the crucial role of the curved portion of the support ring during compression, with the inner side of the curved region experiencing stress concentration. A mathematical model has been established to describe the relationships between the geometry parameters and the radial support property of the BPVSs. Notably, the radius of the neutral layer emerges as a key determinant of radial stiffness. This study is expected to serve as a guideline for the development of BPVSs that can be manufactured using MiM.

Photocurable Nitric Oxide-Releasing Copolyester for the 3D Printing of Bioresorbable Vascular Stents.

The design of bioresorbable vascular stents (BVS) capable of releasing nitric oxide (NO) at the implant site may enable BVS to mimic the antiplatelet, antiproliferative, and pro-endothelial actions of NO, overcoming complications of BVS such as late thrombosis and restenosis. In this study, the fabrication of BVS composed of methacrylated poly(dodecanediol citrate-co-dodecanediol S-nitroso-mercaptosuccinate) (mP(DC-co-DMSNO)), a novel elastomeric, bioabsorbable, and photocurable copolyester, containing covalently bound S-nitrosothiol groups in the carbon backbone of the polymer, is reported. The mP(DC-co-DMSNO) stents are manufactured via photoinduced 3D printing and allow deployment via a self-expansion process from a balloon catheter. After deployment, hydration of the stents triggers the release of NO, which is maintained during the slow hydrolysis of the polymer. Real-time NO release measurements show that by varying the copolyester composition and the strut geometry of the mP(DC-co-DMSNO) stents, it is possible to modulate their NO release rate in the range of 30-52 pmol min-1 cm-2 . Preliminary biological assays in cell culture show that endothelial cells adhere to the surface of the stents and that NO release favors their endothelization. Thus, mP(DC-co-DMSNO) may emerge as a new platform for the fabrication of advanced BVS.

Structure design and mechanical performance analysis of three kinds of bioresorbable poly-lactic acid (PLA) stents.

Vascular stent implantation has become an important choice for the treatment of severe cardiovascular and cerebrovascular blockage. Rational design is vital to ensure the mechanical properties of the vascular stents, which are important both to the implantation and service as for clinical treatment of coronary heart disease. Therefore we proposed a wholly new non-uniform honeycomb stent E and compared with an inverted honeycomb-like shaped stent F and a honeycomb-like shaped stent G. To evaluate their properties, a finite element method (FEM) was used to simulate the implantation process (crimp, crimp recoil, expand, and expand recoil) of these three different kinds of stents. Results showed that the stent E exhibits better mechanical behaviour than the other two stents F and G as far as radial strength and axial shortening performances and that the distribution of equivalent stress among the stent E is more uniform than that among the other two stents F and G. After that, a three-point bending method was used to study the bending flexibility of these three vascular stents. Stent E shows high bending stiffness compared with stents F and G due to the existence of additional support bridges in its structure. This study can be helpful to the rational design of optimizable PLA stents for its practical clinical performance and therefore possibly improve the prognosis of patients.

Development of three-dimensionally printed vascular stents of bioresorbable poly(l-lactide-co-caprolactone).

With the ripening of 3D printing technology and the discovery of a variety of printable materials, 3D-printed vascular stents provide new treatment options for patients with angiocardiopathy. Bioresorbable stent not only combines the advantages of metallic stent and drug-coated balloon, but also avoids the disadvantages of them. 3D printing is also an economical and efficient way to produce stents and makes it possible to construct complex structures. In this study, stents made from poly(l-lactic acid) (PLLA), poly(ε-caprolactone) (PCL) and poly(l-lactide-co-caprolactone) (PLCL) were manufactured by 3D printing and evaluated for radial strength, crystallinity and molecular weight. PLCL copolymerized by different proportions of lactic acid and caprolactone showed different mechanical and degradation properties. This demonstrated the potential of 3D printing as a low-cost and high throughput method for stent manufacturing. The PLLA and PLCL 95/5 stents had similar mechanical properties, whereas PLCL 85/15 and PCL stents both had relatively low radial strength. In general, PLCL 95/5 had a faster degradation rate than PLLA. These two materials were made into peripheral vascular bioresorbable scaffolds (BRS) and further studied by additional bench testing. PLCL 95/5 peripheral BRS had superior mechanical properties in terms of flexural/bending fatigue and compression resistance.

Biosafety and biodegradation studies of AZ31B magnesium alloy carotid artery stent in vitro and in vivo.

Biosafety of AZ31B magnesium (Mg) alloy and the effect of its degradation products on tissues, organs, and whole systems are highly needed to be evaluated before clinical application. This study serves a wide variety of safety evaluations of biodegradable AZ31B alloy on nerve cells. As a result of this in vitro study, the maximum aluminum (Al) ion and Mg ion concentrations in the medium were estimated to be 22 µmol/L and 2.75 mmol/L, respectively, during degradation. In addition, the corresponding cell mortality was observed to be 36% and lower than 5% according to the resistance curves of the cell to Mg and Al ions. Furthermore, the maximum Al ion and Mg ion concentrations in serum and cerebrospinal fluid were detected to be 26.1 µmol/L and 1.2 mmol/L, respectively, for 5 months implantation. Combining the result of in vivo dialysis with the result of ion tolerance assay experiments, the actual death rate of nerve cells is estimated between 4 and 10% in vivo, which is lower than the result of in vitro cytotoxicity evaluation. Moreover, no psychomotor disability during clinical studies is observed. Consequently, stent made of AZ31B alloy with surface treatment is feasible for carotid artery stenosis, and it is safe in terms of cell viability on the nervous system.

A Polymeric Strategy Empowering Vascular Cell Selectivity and Potential Application Superior to Extracellular Matrix Peptides.

Endothelialization of vascular implants plays a vital role in maintaining the long-term vascular patency. In situ endothelialization and re-endothelialization is generally achieved by selectively promoting endothelial cell (EC) adhesion and, meanwhile, suppressing smooth muscle cell (SMC) adhesion. Currently, such EC versus SMC selectivity is achieved and extensively used in vascular-related biomaterials utilizing extracellular-matrix-derived EC-selective peptides, dominantly REDV and YIGSR. Nevertheless, the application of EC-selective peptides is limited due to their easy proteolysis, time-consuming synthesis, and expensiveness. To address these limitations, a polymeric strategy in designing and finding EC-selective biomaterials using amphiphilic ß-peptide polymers by tuning serum protein adsorption is reported. The optimal ß-peptide polymer displays EC versus SMC selectivity even superior to EC-selective REDV peptide regarding cell adhesion, proliferation, and migration of ECs versus SMCs. Study of the mechanism indicates that surface adsorption of bovine serum albumin, an abundant and anti-adhesive serum protein, plays a critical role in the ECs versus SMCs selectivity of ß-peptide polymer. In addition, surface modification of the optimal ß-peptide polymer effectively promotes the endothelialization of vascular implants and inhibits intimal hyperplasia. This study provides an alternative strategy in designing and finding EC-selective biomaterials, implying great potential in the vascular-related biomaterial study and application.

Biodegradable Zn-Cu-Mn alloy with suitable mechanical performance and in vitro degradation behavior as a promising candidate for vascular stents.

Recently, zinc (Zn) alloy has been considered as a promising biodegradable material due to its excellent physiological degradable behavior and acceptable biocompatibility. However, poor mechanical performance limits its application as vascular stents. In this study, novel biodegradable Zn-2.2Cu-xMn (x = 0.4, 0.7, and 1.0 wt%) alloys with suitable mechanical performance were investigated. The effects of Mn addition on microstructure, mechanical properties, and in vitro degradation of Zn-2.2Cu-xMn alloys were systematically investigated. After adding Mn, dynamic recrystallization (DRX) during hot extrusion was promoted, resulting in slightly finer grain size, higher DRXed regions ratio, and weaker texture. And volume fraction and number density of second phase precipitates (micron, submicron, and nano-sized ε and MnZn13 phase) and the concentration of (Cu, Mn) in the matrix were increased. Therefore, Zn-2.2Cu-xMn alloys exhibited suitable mechanical performances (strength >310 MPa, elongation >30%) mainly due to the combination effects of grain refinement, solid solution strengthening, second phase precipitation hardening, and texture weakening. Moreover, the alloys maintained good stability of mechanical properties within 18 months and good elongation over 15% even at a high strain rate of 0.1 s-1. In addition, the alloys presented appropriate in vitro degradation rates in a basically uniform degradation mode and acceptable in vitro cytocompatibility. The above results indicated that the newly designed biodegradable Zn-2.2Cu-0.4Mn alloy with suitable comprehensive mechanical properties, appropriate degradation behavior, and acceptable cytocompatibility is a promising candidate for vascular stents.

Bioresponsive starPEG-heparin hydrogel coatings on vascular stents for enhanced hemocompatibility.

Hydrogel coatings can improve the biocompatibility of medical devices. However, stable surface bonding and homogeneity of hydrogel coatings are often challenging. This study exploits the benefits of biohybrid hydrogels of crosslinked four-armed poly(ethylene glycol) and heparin to enhance the hemocompatibility of cobalt­chromium (CoCr) vascular stents. A bonding layer of dual silane and poly(ethylene-alt-maleic anhydride) (PEMA) treatment was applied to the stent to provide covalent immobilization and hydrophilicity for the homogeneous spreading of the hydrogel. A spray coating technology was used to distribute the aqueous solution of the reactive hydrogel precursors onto the sub-millimeter struts of the stents, where the solution polymerized to a homogeneous hydrogel film. The coating was mechanically stable on the stent after ethanol dehydration, and the stents could be stored in a dry state. The homogeneity and stability of the coating during stent expansion were verified. Quasistatic and dynamic whole blood incubation experiments showed substantial suppression of the pro-coagulant and inflammatory activity of the bare metal by the coating. Translation of the technology to industrial coating devices and future surface modification of stents with anti-inflammatory hydrogels are discussed.

A multi-dimensional non-uniform corrosion model for bioabsorbable metallic vascular stents.

Bioabsorbable metallic vascular stents (BMVSs) are an innovative technological advancement in the medical engineering field of vascular implants. BMVSs have great potential to revolutionize vascular intervention, but the lack of understanding of the construction material's natural corrosion within the body inhibits the use in clinical medicine. In this study, a corrosion function concept for in vivo implants was created to develop a multi-dimensional, non-uniform corrosion model with a larger goal of simulating the mechanical integrity of BMVSs. This proposed corrosion model simulates the corrosion rate and its effects on magnesium (Mg) alloy AZ31 based on continuum damage mechanics. The model was calibrated using three degradation experiments on Mg alloy specimens. These experiments focused on multi-dimensional corrosion, mass loss rate, and mechanical integrity during the corrosion process. Lastly, to verify the applicability of the proposed model, the resulting corrosion behaviors and mechanical characteristics of the BMVSs were implemented into a finite element framework to produce an overarching simulation of the BMVS's degradation in vivo. The results of the experiments and simulations revealed a proportional link between the corrosion of BMVSs and the number of exposed surfaces. A non-linear decline in mechanical integrity with increasing mass loss was also discovered through experimentation and modeling. Furthermore, the model and simulation can provide some details about changes in morphology and mechanics during BMVS corrosion. This work gives new insights into accurately modeling for BMVS degradation and can be used to optimize product development of BMVSs. STATEMENT OF SIGNIFICANCE: Bioabsorbable metallic vascular stents (BMVSs) are an innovative technological advancement in the medical engineering field of vascular implants. Despite BMVSs have great potential to revolutionize vascular intervention, the lack of understanding of the construction material's natural corrosion within the body inhibits their use in clinical medicine. In this study, a novel multi-dimensional non-uniform corrosion model was proposed to unveil the mechanisms during the in vivo degradation of bioabsorbable metallic implants, which can accurately capture the overlooked changes in morphology and mechanics during BMVS corrosion. This work provides a technical solution to enhance the modeling accuracy in BMVS degradation and can be further used to optimize the design of BMVSs in the future.

Covalent immobilization of biomolecules on stent materials through mussel adhesive protein coating to form biofunctional films.

It is widely accepted that surface biofunctional modification may be an effective approach to improve biocompatibility and confer new bioactive properties on biomaterials. In this work, mussel adhesive protein (MAP) was applied as a coating on 316 L stainless steel substrates (316 L SS) and stents, and then either immobilized VEGF or CD34 antibody were added to create biofunctional films. The properties of the MAP coating were characterized by scanning electron microscope (SEM), atomic force microscope (AFM) and a water contact angle test. Universal tensile testing showed that the MAP coating has adequate adhesion strength on a 316 L stainless steel material surface. Subsequent cytotoxicity and hemolysis rate tests showed that the MAP coatings have good biocompatibility. Moreover, using N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysulfosussinimide (EDC/NHS) chemistry, VEGF and CD34 antibody were immobilized on the MAP coatings. The amount and immobilized yield of VEGF on the MAP coatings were analyzed by enzyme-linked immuno-assays (ELISA). Finally, an endothelial cells culture showed that the VEGF biofunctional film can promote the viability and proliferation of endothelial cells. An in vitro CD34+ cells capturing test also verified the bioactive properties of the CD34 antibody coated stents. These results showed that the MAP coatings allowed effective biomolecule immobilization, providing a promising platform for vascular device modification.

The effect of intrinsic characteristics on mechanical properties of poly(l-lactic acid) bioresorbable vascular stents.

Poly(L-lactic acid) (PLLA) is currently the bioresorbable polymer of choice for vascular stents with its superior biocompatibility and mechanical properties. However, it is still difficult to enhance the radial supporting capacity of PLLA stents without increasing the strut thickness. In this study, the performance of laser-cut thin-strut stents from two groups of PLLA tubes are investigated. We considered two groups of PLLA tubes. Group 1 indicates the longitudinally stretched from original 150-µm-thick tubes, and Group 2 indicates the directly thinned from original 150-µm-thick tubes. Three stages of mechanical tests were conducted in this study, which are defined as tensile tests of dog-bone specimens, radial loading tests of tubes and radial loading tests of stents. The results suggest that Group 2 has higher radial supporting capacity than Group 1 with the same wall thickness. This work serves as a basis for manufacturing thin-strut stents with sufficient radial supporting capacity.

Elastic recovery of polymeric braided stents under cyclic loading: Preliminary assessment.

Over the last decades, stents have been largely used to treat vascular diseases such as coronary artery or peripheral vessel stenosis. Among the solutions which are commercially available to treat vascular stenosis, metallic stents represent the gold standard. However, issues such as restenosis, corrosion and fractures have been reported with these devices and are especially due to the material which is used. Braided polymeric stents could present an alternative to replace metallic stents especially in peripheral vessels where flexibility is required. Among polymeric materials, polyethylene terephthalate (PET), could be a good candidate as its biocompatibility has already been widely proven especially in the field of cardiovascular applications. Moreover, braided devices have been already used for the stenting of peripheral zones, providing locally outstanding flexibility due to the discontinuity of these structures. The goal of this work was to evaluate the radial strength and the recovery performances of polymeric braided stents made from PET monofilaments. In particular, the behavior of these stents under repeated cyclic radial compression loading was assessed and compared to results obtained with a metallic braided stent of same diameter. Results show that polymeric braided stents provide 100% elastic recovery after 20% diameter compression over 2000 repetitive loading cycles. However, radial strength goes slightly down with cycling, which points out that friction occurs in the braid. It comes out from the study that a braided polymer stent shows suitable mechanical behavior compared to a metallic stent over cyclic loading up to 2000 cycles. Moreover, it is shown that the mechanical behavior of these stents depend highly on the braid angle.

Nano-biomaterials for cardiovascular applications: Clinical perspective.

Cardiovascular diseases, including ischemic heart disease and stroke, are responsible for nearly 25% of all deaths worldwide. Globally, their prevalence continues to increase, in spite of enormous progress in cardiovascular diagnostics and therapy. For therapeutic and regenerative purposes, biomaterials promise solutions with multiple advantages over synthetic materials. Furthermore, their easy availability as nanoformulations recommends their application as drug carriers or protective nanoshells improving the biocompatibility of imaging agents. In this work, we review the most promising and clinically meaningful scientific reports with regard to (nano)biomaterials with particular focus on potential improvements of existing, and development of novel constructs for cardiovascular applications.

Development and application of metal materials in terms of vascular stents.

BACKGROUND: With life pace accelerated, poor diet habits developed, psychological burden enhanced and many other factors, the incidence of coronary heart disease, atherosclerosis and other cardiovascular cerebrovascular diseases has been increased year by year, which are serious threat to human health. OBJECTIVE: Provide relational references for the similar researchers after metal stent materials were reviewed and prospected. METHODS: This paper reviews the development and application of metal materials in terms of vascular stents, focusing on the advantages and disadvantages of 316L stainless steel, nitinol super-elastic alloys, cobalt-based alloys (Co-Cr-Ni-Mo-Mn), magnesium-based alloy, iron-based alloys and tantalum metal stents as well as in clinical practice research and application. RESULTS: Recognize the advantages and disadvantages of different metal stent materials as well as in clinical practice research and application. CONCLUSIONS: Although metal stents have been widely used in clinical practice, there are still many problems to be solved, especially to improve mechanical properties and biological activity. Strong immune rejection is also a problem. Therefore, it will be a significant direction for future material research to treat surface modification, further improve the biocompatibility, reduce the thrombosis and completely eliminate the rejection and vascular restenosis. In addition, the stent materials should be developed toward controllable degradation and special features in the future.

MRI-compatible Nb-60Ta-2Zr alloy for vascular stents: Electrochemical corrosion behavior in simulated plasma solution.

Using revised simulated body fluid (r-SBF), the electrochemical corrosion behavior of an Nb-60Ta-2Zr alloy for MRI compatible vascular stents was characterized in vitro. As indicated by XPS analysis, the surface passive oxide film of approximately 1.3nm thickness was identified as a mixture of Nb2O5, Ta2O5 and ZrO2 after immersion in the r-SBF. The Nb-60Ta-2Zr alloy manifests a low corrosion rate and high polarization resistance similar to pure Nb and Ta, as shown by the potentiodynamic polarization curves and EIS. Unlike 316L stainless steel and the L605 Co-Cr alloy, no localized corrosion has been detected. Semiconducting property of passive film on the Nb-60Ta-2Zr alloy was identified as the n-type, with growth mechanism of high-field controlled growth. The excellent corrosion resistance in simulated human blood enviroment renders the Nb-60Ta-2Zr alloy promising as stent candidate material.