Effects of Tapered-Strut Design on Fatigue Life Enhancement of Peripheral Stents.

Peripheral stent could fracture from cyclic loadings as a result of our blood pressures or daily activities. Fatigue performance has therefore become a key issue for peripheral stent design. A simple yet powerful tapered-strut design concept for fatigue life enhancement was investigated. This concept is to move the stress concentration away from the crown and re-distribute the stresses along the strut by narrowing the strut geometry. Finite element analysis was performed to evaluate the stent fatigue performance under various conditions consistent with the current clinical practice. Thirty stent prototypes were manufactured in-house by laser with a series of post-laser treatments, followed by the validation of bench fatigue tests for proof of concept. FEA simulation results show that the fatigue safety factor of the 40% tapered-strut design increased by 4.2 times that of a standard counterpart, which was validated by bench tests with 6.6-times and 5.9-times fatigue enhancement at room temperature and body temperature, respectively. Bench fatigue test results agreed very well with the increasing trend predicted by FEA simulation. The effects of the tapered-strut design were significant and could be considered as an option for fatigue optimization of future stent designs.

Detection of Carotid Artery Stenosis Based on Video Motion Analysis for Fast Screening.

Background Carotid artery stenosis (CAS) is a common cause of ischemic stroke, and the early detection of CAS may improve patient outcomes. Carotid Doppler ultrasound is commonly used to diagnose CAS. However, it is costly and may not be practical for regular screening practice. This article presents a novel noninvasive and noncontact detection technique using video-based motion analysis (VMA) to extract useful information from subtle pulses on the skin surface to screen for CAS. Methods and Results We prospectively enrolled 202 patients with prior carotid Doppler ultrasound data. A short 30-second video clip of the neck was taken using a commercial mobile device and analyzed by VMA with mathematical quantification of the amplitude of skin motion changes in a blinded manner. The first 40 subjects were used to set up the VMA protocol and define cutoff values, and the following 162 subjects were used for validation. Overall, 54% of the 202 subjects had ultrasound-confirmed CAS. Using receiver operating characteristic curve analysis, the area under the curve of VMA-derived discrepancy values to differentiate patients with and without CAS was excellent (area under the curve, 0.914 [95% CI, 0.874-0.954]; P<0.01). The best cutoff value of VMA-derived discrepancy values to screen for CAS was 5.1, with a sensitivity of 87% and a specificity of 87%. The diagnostic accuracy was consistently high in different subject subgroups. Conclusions A simple and accurate screening technique to quickly screen for CAS using a VMA system is feasible, with acceptable sensitivity and specificity.

Novel Blood Clot Retriever for Ischemic Stroke.

Stroke is the second leading cause of death in the world. Ischemic stroke, caused by the blockage of intracranial arteries, accounts for approximately 80% of strokes. Among this proportion, acute ischemic stroke, usually caused by the sudden formation of blood clots, can cause fatal blockages in arteries. We proposed a unique blood clot retriever for the treatment of acute ischemic stroke, and conducted a series of tasks, including design, computer simulation, prototyping, and bench testing, for the proof of concept. Unlike most blood clot retrievers used today, our novel design deviates from traditional stent-like blood clot retrievers and uses large closed cells, irregular spikes, and strut protrusions to achieve maximum entanglement for better retrieval performance. Experimental results showed that the retrieval rate of our blood clot retriever was 79%, which demonstrated the feasibility of our new design concept.

A Single-Connector Stent Antenna for Intravascular Monitoring Applications.

Recently, smart stents have been developed by integrating various sensors with intravascular stents for detecting vascular restenosis or monitoring intravascular biomedical conditions such as blood pressure or blood flow velocity. The information on biomedical signals is then transmitted to external monitoring systems via wireless communications. Due to the limited volumes of blood vessels and limited influence of blood flow, antennas with good radiation performance are required for intravascular applications. In this paper, we propose a stent antenna composed of multiple rings containing crowns and struts, where each ring is connected with one connector. Unlike a conventional stent, wherein each ring is connected with several connectors, the single connector prevents the random distribution of electrical current and thus achieves good radiation performance. The implantable stent antenna is designed for the frequency range of 2 to 3 GHz for minimum penetration loss in the human body and tissues. Mechanical FEM simulations were conducted to ensure that the mechanical deformation was within specific limits during balloon expansions. A prototype was fabricated with laser cutting techniques and its radiation performance experimentally characterized. It was demonstrated that the fabricated stent antenna had an omnidirectional radiation pattern for arbitrary receiving angles, a gain of 1.38 dBi, and a radiation efficiency of 74.5% at a resonant frequency of 2.07 GHz. The main contribution of this work was the manipulation of the current distributions of the stent for good EM radiation performances which needed to be further examined while inserted inside human bodies. These research results should contribute to the further development of implantable wireless communications and intravascular monitoring of biomedical signals such as blood pressure and blood flow velocity.

Rhombic-Shaped Channel Stent with Enhanced Drug Capacity and Fatigue Life.

A drug-eluting stent with rhombic-shaped drug reservoirs is proposed, aimed at providing long-term drug delivery and enhanced fatigue life. Unique rhombic-shaped reservoirs or channels on the stent struts can increase the total drug capacity and improve the stress distribution for longer fatigue life, without compromising other important clinical attributes. Our rhombic-shaped channel stent increases the total drug capacity by multiple times. Its fatigue safety factor, even with the large rhombic cutouts on the stent struts, could be 50% higher than that of the conventional drug-eluting stent. A pulsed fiber-optic laser and a series of expansions and heat treatments were used to make the first prototype of our rhombic-shaped channel stent. This new concept may open up a wide variety of new treatment options and opportunities for the medical industry in the future.

A Novel Nitinol Spherical Occlusion Device for Liver Cancer.

Liver cancer or hepatic cancer is a cancer that originates in the liver. It is formed from either the liver itself or from structures within the liver, including blood vessels or the bile duct. Liver cancer can be a life-threatening condition, but it may be cured if found early. Hepatic artery embolization is one of the treatment options involving the injection of substances to reduce the blood flow to cancer cells in the livers of patients with tumors that cannot be removed by surgery; however, this treatment has some limitations. In this paper, we propose a novel nitinol "spherical occlusion device" concept, the first of its kind in the world. Our proposed spherical occlusion device is able to reduce the blood flow to cancer cells by deploying it in the upstream hepatic artery supplying blood to the liver. Moreover, it could carry multiple chemotherapy or radioactive drugs for delivery directly to the target site. Nitinol alloy was chosen as the device material due to its excellent super-elastic property. Computational models were developed to predict the mechanical response of the device during manufacturing and deployment procedures, as well as its hemodynamic behavior. Simulation results showed that the presence of the spherical occlusion device with 14%-27% metal density deployed at the upstream location of the right hepatic artery had significant occlusion effects, with the average blood flow rate cut down by 30%-50%. A pulsed fiber laser and a series of expansions and heat treatments were developed to make the first prototype of the spherical occlusion device for the demonstration of our novel concept.

Investigation of fibrous cap stresses on vulnerable plaques leading to heart attacks.

Rupture-prone plaques in the coronary arteries, called ``vulnerable plaques'', are recognized as the key factor in acute myocardial infarction. Vulnerable plaques have a thin fibrous cap over a large fatty core and are highly susceptible to rupture. In general, this type of plaque rupture is mainly associated with stress concentrated on the fibrous cap. Fibrous cap stresses are counted among the most important factors in the plaque rupture process and must be taken into consideration when assessing the plaque vulnerability leading to heart attacks. The objective of this paper was to investigate the effects of nitinol stent deployment on the morphological changes of vulnerable plaques and then to propose a new stent design concept for effectively reducing fibrous cap stresses and the associated rupture risk. The deployment of a self-expanding nitinol stent was modeled, and the resulting stress distribution on the fibrous cap was investigated. The fibrous cap stresses were more uniformly distributed and the maximum stress was reduced by 13% when the crown number of the stent was increased. This study demonstrates an excellent approach to stent design that could effectively reduce the risk of a vulnerable plaque rupturing and causing a heart attack.

Investigation of fibrous cap stresses on vulnerable plaques leading to heart attacks.

Rupture-prone plaques in the coronary arteries, called ``vulnerable plaques'', are recognized as the key factor in acute myocardial infarction. Vulnerable plaques have a thin fibrous cap over a large fatty core and are highly susceptible to rupture. In general, this type of plaque rupture is mainly associated with stress concentrated on the fibrous cap. Fibrous cap stresses are counted among the most important factors in the plaque rupture process and must be taken into consideration when assessing the plaque vulnerability leading to heart attacks. The objective of this paper was to investigate the effects of nitinol stent deployment on the morphological changes of vulnerable plaques and then to propose a new stent design concept for effectively reducing fibrous cap stresses and the associated rupture risk. The deployment of a self-expanding nitinol stent was modeled, and the resulting stress distribution on the fibrous cap was investigated. The fibrous cap stresses were more uniformly distributed and the maximum stress was reduced by 13% when the crown number of the stent was increased. This study demonstrates an excellent approach to stent design that could effectively reduce the risk of a vulnerable plaque rupturing and causing a heart attack.

Effects of stent design on new clinical issue of longitudinal stent compression in interventional cardiology.

In recent years, interventional cardiologists have discussed over a new clinical issue called longitudinal stent compression (LSC), a failure mode not previously observed in coronary stents. This phenomenon occurs when the physician attempts to cross a deployed stent with a second device, causing the stent to dramatically shorten when two devices are accidentally entangled. While this phenomenon has been observed with a number of stent platforms, it seems more common with the Element stent. In this paper, a computational LSC model using finite element analysis was developed. A systematic investigation was conducted in attempts to quantify individual contribution of the stent design pattern, connector number, design parameter, and connector location on LSC. Computational simulations were performed on two representative coronary stents resembling Element and Endeavor for comparison. Simulation results show that the connector number plays the most significant role in LSC. The LSC could be easily tripled or quadrupled for the same stent design simply by increasing the connector number from two to three. The design pattern and design parameter play a secondary role in LSC, with the LSC improved by up to 30 and 65 %, respectively. It was also found that the LSC could be doubled for the Element stent simply by rearranging its connector location. This small design tweak could help improve the current Element LSC significantly, while still maintaining the majority of its excellent deliverability. These findings could provide great insights into this new clinical issue and help optimize future stent design to reduce the associated risk involved in LSC.

New clinical failure mode triggered by a new coronary stent design.

Longitudinal stent compression (LSC) is a new failure mode not previously observed in coronary stents. This phenomenon occurs when the physician tries to cross the deployed stent with other devices. While this phenomenon has been observed with a number of stent designs, it seems more common with the Element stent. A computational LSC model using finite element analysis was developed. Computational simulations were performed on two representative coronary stents in the current market resembling Element and Endeavor in attempts to quantify individual contribution of the stent design pattern and connector number on LSC. Simulation results show that the connector number plays the most significant role in the development of the LSC issue. The LSC could be easily tripled for the Element stent simply by increasing the connector number from two to three. The stent design pattern plays a secondary role in LSC. The LSC could be improved by up to 30% when the design pattern changes from the offset peak-to-peak design (Element) to the peak-to-peak design (Endeavor). Conclusions obtained from this paper may help clinical stent selection and future stent design optimization to reduce the risk associated with longitudinal stent compression.

An intriguing design concept to enhance the pulsatile fatigue life of self-expanding stents.

Intravascular stenting has emerged as the primary treatment for vascular diseases and has received great attention from the medical community since its introduction two decades ago. The endovascular self-expanding stent is used to treat peripheral artery diseases; however, once implanted, these stents suffer from various cyclic motions caused by pulsatile blood pressure and daily activities. Due to this challenging environment, fatigue performance has become a critical issue for stent design. In this paper, a simple yet intriguing concept of stent design aimed at enhancing pulsatile fatigue life is investigated. The concept of this design is to shift the highly concentrated stresses/strains away from the crown and re-distribute them along the stress-free bar arm by tapering its strut width. Finite element models were developed to evaluate the mechanical integrity and pulsatile fatigue resistance of the stent to various loading conditions. Results show that the fatigue safety factor jumped to 2.5-3.0 times that of the standard stent with constant strut width. This is astonishing considering that the stent profile and scaffolding were not compromised. The findings of this paper provide an excellent approach to the optimization of future stent design to greatly improve stent fatigue performance.

Thermo-induced shape-memory PEG-PCL copolymer as a dual-drug-eluting biodegradable stent.

In this work, a thermo-induced shape-memory drug-eluting stent (SMDES) has been developed by cross-linking PEG-PCL copolymer (cPEG-PCL). The stent is able to perform the shape-memory effect from a temporary linear form to a permanent spiral shape with the transition temperature close to body temperature. The stent incorporates a controlled dual drug-release system for the purpose of preventing in-stent restenosis of the vessel for short- and long-term therapeutic effects. From the results, (1)H NMR and GPC indicate that the compositions of PEG-PCL block copolymers are similar to the feed ratios of PEG/ε-CL. A Young's modulus of the cPEG-PCL stent can be achieved that ranges from tens to one hundred megapascals by modulation of the mixing ratio of PEG/PCL. The cPEG-PCL stent is demonstrated to recover to its permanent shape with a high fixing ratio (>99%), recovery ratio (>90%), and recovery time (<10 s). DSC data reveals that the transition temperature is around body temperature (40 °C). Cytotoxicity tests prove that the cPEG-PCL_6040 stent has good biocompatibility. In vitro degradation tests show that the cPEG-PCL_6040 stent undergoes a bulk degradation of 47% after 60 days of incubation under flow conditions. Platelet adhesion and smooth muscle cell proliferation were significantly inhibited by coculture with a mitomycin C/curcumin-eluting stent as a result of the release of curcumin for antiplatelet adhesion during the initial 2 weeks followed by long-term inhibition of smooth muscle cell hyperproliferation for 60 days via mitomycin C. After 60 days of incubation in a bioreactor, the appearance of the stent remains intact and shows no signs of recoiling or collapse.

Vapor-based tri-functional coatings.

The tri-functional coating synthesized via CVD copolymerization is comprised of distinguished anchoring sites of acetylene, maleimide, and ketone that can synergically undergo specific conjugation reactions to render surfaces with distinct biological functions, simultaneously. In addition, these tri-functional coatings can be fabricated in a micro-structured fashion on non-conventional surfaces.

Effects of through-hole drug reservoirs on key clinical attributes for drug-eluting depot stent.

Atherosclerosis, a condition related to cholesterol build-up and thickening of the inner wall of the artery, narrows or occludes the artery lumen. The drug-eluting stent is a major breakthrough for the treatment of such coronary artery diseases. In recent years, another innovative variation of the drug-eluting stent with drug reservoirs has been introduced. It allows programmable drug delivery with spatial and temporal control and has several potential advantages over traditional drug-eluting stents. However, creating such reservoirs on the stent struts may weaken the stent scaffolding and compromise its mechanical integrity. In this paper, the effects of these micro-sized through-hole drug reservoirs on several key clinically relevant functional attributes of the depot stent were investigated. Finite element models were developed to predict the mechanical integrity of a balloon-expandable stent at various stages such as manufacturing and deployment, as well as the stent radial strength and fatigue life. Results show that (1) creating drug reservoirs on a stent could impact the stent fatigue resistance to some degree; (2) drug reservoirs on the stent crowns led to much greater loss in all key clinical attributes than reservoirs on other locations; (3) reservoir shape change resulted in little differences in all key clinical attributes; (4) for the same drug loading capacity, larger and fewer reservoirs yielded lower equivalent plastic strain and radial strength but higher fatigue safety factor; and (5) the proposed depot stent was proven to be a feasible design. Its total drug capacity could be tripled with acceptable marginal trade-off in key clinical attributes. These results can serve as the guidelines to help future stent designs to achieve the best combination of stent mechanical integrity and smart drug delivery in the future, thereby opening up a wide variety of new treatment potentials and opportunities.

Assessment of mechanical integrity for drug-eluting renal stent with micro-sized drug reservoirs.

The drug-eluting stent (DES) has become the gold standard worldwide for the treatment of cardiovascular diseases. In recent years, an innovative variation of the DES with micro-sized drug reservoirs has been introduced. It allows programmable drug delivery with both spatial and temporal control and has several potential advantages over traditional DESs. However, creating such reservoirs on the stent struts may weaken the structure of the stent scaffolding and compromise its mechanical integrity. In this study, we propose to use this innovative stent concept in the renal indication for potential treatment of both renal artery stenosis (upstream) and its associated kidney diseases (downstream) at the same time. The effects of these micro-sized drug reservoirs on several key clinically relevant functional attributes of the drug-eluting renal stent were systematically and quantitatively investigated. Finite element models were developed to predict the mechanical integrity of a balloon-expandable stent at various stages. Results show that (1) creating drug reservoirs on a stent could impact the stent fatigue resistance to certain degrees; (2) drug reservoirs on the stent crowns lead to greater loss in all key stent attributes than reservoirs on either bar arms or connectors and (3) the proposed optimised depot stent was proven to be feasible and could triple drug capacity than the current DESs, with marginal trade-off in its key clinical attributes. These results can serve as the guidelines to help future stent designs to achieve the best combination of stent structural integrity and smart drug delivery in the future.

Rigidity guided cell attachment on inkjet-printed patterns.

A new approach is presented to control cell attachment behavior on biocompatible substrates. Multiple layers of polylactic acid (PLA) were inkjet-printed on dry alginate films to create composite surfaces with rigidity variation. The printed films were submerged in cell culture medium and fibroblast 3T3-L1 cells were cultured on the printed films. 3T3-L1 cells were found to preferentially adhere on PLA surfaces with higher rigidity. The same approach was also used to create various cell attachment patterns. This study provides a new methodology to fabricate biodegradable matrix for favorable cell adhesion or patterning.

Respiration-induced kidney motion on cobalt-chromium stent fatigue resistance.

During normal breathing, the kidneys move up and down due to the diaphragm motion and the renal artery subsequently experiences bending at or close to its point of fixation to the aorta. The impact of this kidney motion on implanted stent fatigue performance was not well understood in the past. Previous study from the authors on an 18-mm long single cobalt-chromium stent showed that the change in bending angle was minor during simulated respiration-induced kidney motion on cadavers. Finite Element Analysis revealed excellent fatigue resistance of the studied cobalt-chromium stent under simulated respiratory motion for the single stent configuration. In this article, the study was extended further to the overlapped stent configuration where a physician deploys two stents overlapping at the stent ends to fully cover a long lesion. Fluoroscopic images showed that the change in bending angle during simulated respiration-induced kidney motion on cadavers was more significant when two cobalt-chromium stents were overlapped. Calculated data of the Goodman analysis for the overlapped stents migrated toward the Goodman diagram failure line, indicating lower fatigue resistance during respiration when compared to a single stent.