Mahdis Shayan

An overview of thin film nitinol endovascular devices

Thin film nitinol has unique mechanical properties (e.g., superelasticity), excellent biocompatibility, and ultra-smooth surface, as well as shape memory behavior. All these features along with its low-profile physical dimension (i.e., a few micrometers thick) make this material an ideal candidate in developing low-profile medical devices (e.g., endovascular devices). Thin film nitinol-based devices can be collapsed and inserted in remarkably smaller diameter catheters for a wide range of catheter-based procedures; therefore, it can be easily delivered through highly tortuous or narrow vascular system. A high-quality thin film nitinol can be fabricated by vacuum sputter deposition technique. Micromachining techniques were used to create micro patterns on the thin film nitinol to provide fenestrations for nutrition and oxygen transport and to increase the devices flexibility for the devices used as thin film nitinol covered stent. In addition, a new surface treatment method has been developed for improving the hemocompatibility of thin film nitinol when it is used as a graft material in endovascular devices. Both in vitro and in vivo test data demonstrated a superior hemocompatibility of the thin film nitinol when compared with commercially available endovascular graft materials such as ePTFE or Dacron polyester. Promising features like these have motivated the development of thin film nitinol as a novel biomaterial for creating endovascular devices such as stent grafts, neurovascular flow diverters, and heart valves. This review focuses on thin film nitinol fabrication processes, mechanical and biological properties of the material, as well as current and potential thin film nitinol medical applications.

An in vivo pilot study of a microporous thin film nitinol-covered stent to assess the effect of porosity and pore geometry on device interaction with the vessel wall

Sputter-deposited thin film nitinol constructs with various micropatterns were fabricated to evaluate their effect on the vessel wall in vivo when used as a covering for commercially available stents. Thin film nitinol constructs were used to cover stents and deployed in non-diseased swine arteries. Swine were sacrificed after approximately four weeks and the thin film nitinol-covered stents were removed for histopathologic evaluation. Histopathology revealed differences in neointimal thickness that correlated with the thin film nitinol micropattern. Devices covered with thin film nitinol with a lateral × vertical length = 20 × 40 µm diamond pattern had minimal neointimal growth with well-organized cell architecture and little evidence of ongoing inflammation. Devices covered with thin film nitinol with smaller fenestrations exhibited a relatively thick neointimal layer with inflammation and larger fenestrations showed migration of inflammatory and smooth muscle cells through the micro fenestrations. This “proof-of-concept” study suggests that there may be an ideal thin film nitinol porosity and pore geometry to encourage endothelialization and incorporation of the device into the vessel wall. Future work will be needed to determine the optimal pore size and geometry to minimize neointimal proliferation and in-stent stenosis.

In Vitro Study of a Superhydrophilic Thin Film Nitinol Endograft that Is Electrostatically Endothelialized in the Catheter Prior to the Endovascular Procedure

Electrostatic endothelial cell seeding has evolved as an exceptional technique to improve the efficiency of cell seeding in terms of frequency of attached cells and the amount of cell adhesion for the treatment of vascular diseases. In the recent times, both untreated and superhydrophilic thin film nitinol (TFN) have exhibited strong prospects as substrates for creation of small-diameter endovascular grafts due to their hallmark properties of superelasticity, ultra low-profile character, and grown hemocompatible oxide layer with the presence of a uniform endothelial layer on the surface. The purpose of the current study is to understand the effects of endothelial cell seeding parameters (i.e., applied voltage, incubation time, substrate chemistry, and cell suspension solution) to investigate the cell seeding phenomenon and to improve the cell adhesion and growth on the TFN surface under electrostatic transplantation. Both parallel plate and cylindrical capacitor models were used along with the Taguchi Design of Experiment (DOE) methods to design in vitro test parameters. A novel in vitro system for a cylindrical capacitor model was created using a micro flow pump, micro incubation system, and silicone tubings. The augmented endothelialization on thin film nitinol was developed to determine the effect of cell seeding and deployed in a 6 Fr intravascular catheter setup. Cell viability along with morphology and proliferation of adhered cells were evaluated using fluorescent and scanning electron microscopy. Our results demonstrated that the maximum number of cells attached on STFN in the catheter was observed in 5 V with the 2 h exposure of in the cell culture medium (CCM) solution. The condition showed 5 V voltage with 0.68 × 10−6 µC electrostatic charge and 5.11 V·mm−1 electric field. Our findings have first demonstrated that the electrostatic endothelialization on the superhydrophilic thin film nitinol endograft within the catheter prior to the endovascular procedure could enhance the biocompatibility for low-profile endovascular applications.

Wireless, intraoral hybrid electronics for real-time quantification of sodium intake toward hypertension management

Significance We introduce a soft, low-profile, intraoral electronics that offers continuous real-time monitoring of sodium intake via long-range wireless telemetry. The stretchable, hybrid electronic system integrates chip-scale components and microstructured sodium sensors with stretchable interconnects, together in an ultrasoft, breathable, microporous membrane. The quantitative computational and experimental studies of antenna performance optimize the wireless electronics, offering consistent functionality with minimal loss during multimodal deformation. Examples of in vivo study with human subjects demonstrate a highly sensitive, real-time quantification of sodium intake. Recent wearable devices offer portable monitoring of biopotentials, heart rate, or physical activity, allowing for active management of human health and wellness. Such systems can be inserted in the oral cavity for measuring food intake in regard to controlling eating behavior, directly related to diseases such as hypertension, diabetes, and obesity. However, existing devices using plastic circuit boards and rigid sensors are not ideal for oral insertion. A user-comfortable system for the oral cavity requires an ultrathin, low-profile, and soft electronic platform along with miniaturized sensors. Here, we introduce a stretchable hybrid electronic system that has an exceptionally small form factor, enabling a long-range wireless monitoring of sodium intake. Computational study of flexible mechanics and soft materials provides fundamental aspects of key design factors for a tissue-friendly configuration, incorporating a stretchable circuit and sensor. Analytical calculation and experimental study enables reliable wireless circuitry that accommodates dynamic mechanical stress. Systematic in vitro modeling characterizes the functionality of a sodium sensor in the electronics. In vivo demonstration with human subjects captures the device feasibility for real-time quantification of sodium intake, which can be used to manage hypertension.

A novel low-profile thin-film nitinol/silk endograft for treating small vascular diseases

Since the introduction of various endovascular graft materials such as expanded polytetrafluoroethylene (e-PTFE) and Dacron® polyester, they have been rapidly applied in endovascular devices for treating a variety of clinical situations. While present endovascular grafts have been successful in treating large blood vessels, there are still significant challenges and limitations for small and tortuous vessels to their use. Recently, our group has demonstrated the potential to use thin-film nitinol (TFN) as a novel material to develop endografts used in the treatment of a wide range of small vascular diseases because TFN is ultralow profile (that is, a few micrometers thick), relatively thromboresistant, and superelastic. While TFN has shown superior thromboresistance, its surface endothelialization is not rapid and sufficient. Therefore, our laboratory has been exploring the feasibility of using thin-film silk as a novel coating for facilitating rapid and confluent endothelial cell growth. The purpose of this study is to fabricate a low-profile composite endograft using thin layers of nitinol and silk, and to evaluate both thrombogenicity as well as endothelial cell and smooth muscle cell responses. This study also evaluates the functionality of the composite endograft using an in vitro blood circulation model.

Assessment of endothelial cell growth behavior in thin film nitinol

Growing clinical needs for less invasive endovascular treatments necessitate the development of advanced biomaterials that exhibit low-profile and enhanced biocompatible properties. One of the endovascular devices is a stent graft, which contains a metallic backbone, covered with thin polymeric membranes such as Dacron® and expandable polytetrafluoroethylene (ePTFE). This device has been widely used for treating various vascular diseases and injuries. While the commercial materials including Dacron® and ePTFE have demonstrated a good feasibility, they were found to induce inflammatory vessel wall reactions with neointimal hyperplasia. Consequently, it causes re-narrowing of the lumen space and thrombogenic issues that ultimately lead the treatment failure. In this paper, we introduced a thin film nitinol (TFN) as an alternative graft material and evaluated the growth behavior of endothelial cells (EC) both qualitatively and quantitatively. As a proof-of-concept study, both untreated nonpatterned film (TFN) and surface treated TFN (S-TFN) materials were used. We compared the adhesion, growth, and proliferation of ECs on a solid (non-patterned) TFN with the two most widely-used commercial graft materials (Dacron® and ePTFE). The in vitro experimental results showed better adhesion and growth of ECs on TFN materials than either ePTFE or Dacron®. Specifically, S-TFN showed approximately twice number of ECs attached on the surface than any other materials tested in this study. In addition, in vivo swine study demonstrated that ECs had a relatively high proliferation on the micropatterrned S-TFN with ~50% surface coverage within two weeks. Both in vitro and in vivo study results of cell growth suggested that TFN materials could be a promising graft material for low-profile endovascular devices.

Use of Micropatterned Thin Film Nitinol in Carotid Stents to Augment Embolic Protection

Stenting is an alternative to endarterectomy for the treatment of carotid artery stenosis. However, stenting is associated with a higher risk of procedural stroke secondary to distal thromboembolism. Hybrid stents with a micromesh layer have been proposed to address this complication. We developed a micropatterned thin film nitinol (M-TFN) covered stent designed to prevent thromboembolism during carotid intervention. This innovation may obviate the need or work synergistically with embolic protection devices. The proposed double layered stent is low-profile, thromboresistant, and covered with a M-TFN that can be fabricated with fenestrations of varying geometries and sizes. The M-TFN was created in multiple geometries, dimensions, and porosities by sputter deposition. The efficiency of various M-TFN to capture embolic particles was evaluated in different atherosclerotic carotid stenotic conditions through in vitro tests. The covered stent prevented emboli dislodgement in the range of 70%–96% during 30 min duration tests. In vitro vascular cell growth study results showed that endothelial cell elongation, alignment and growth behaviour silhouettes significantly enhance, specifically on the diamond-shape M-TFN, with the dimensions of 145 µm × 20 µm and a porosity of 32%. Future studies will require in vivo testing. Our results demonstrate that M-TFN has a promising potential for carotid artery stenting.

Smart guidewires for smooth navigation in neurovascular intervention

A smart guidewire using nitinol materials was designed, manufactured and evaluated the device functionality, such as bending performance, trackability, thermal effects, and thrombogenic response. Two types of nitinol material were partially used to enhance the guidewire trackability. A proposed smart guidewire system uses either one- or two-way shape-memory alloy nitinol (1W-SMA, 2W-SMA) wires (0.015, 381µm nitinol wire). Bending stiffness was measured using in vitro test system, which contains the NI USB-9162 data logger and LabView Signal Express 2010. Temperature distribution and displacement were evaluated via recording a 60Hz movie using a SC325 camera. Hemocompatibility was evaluated by scanning electron microscopy after one heating cycle of nitinol under the Na-citrate porcine whole blood circulation. A smart guidewire showed 30 degrees bending after applying or disconnecting electrical current. While the temperature of the nitinol wires increased more than 70 °C, the surrounding temperature with the commercially available catheter coverings showed below human body temperature showing 30 ̴ 33 °C. There was no significant platelet attachment or blood coagulation when the guidewire operates. Novel smart guidewires have been developed using shape memory alloy nitinol, which may represent a novel alternative to typical commercially available guidewires for interventional procedures.

Computational analysis of the regenerated knee structure after bone marrow stimulation techniques

Bone marrow stimulation techniques, such as abrasion arthroplasty or microfracture, have been widely used for repairing cartilage; however, the mechanical stress analysis of these surgical techniques has not been fully investigated. In this study, finite element analysis was used to investigate stresses produced in complex structures (e.g., cartilage, subchondral bone and trabecular bone) using 2D knee structural models. Abrasion arthroplasty creates global damages only in subchondral bone, but, microfracture technique creates local damages in both trabecular and subchondral regions. Although stresses do not significantly change in trabecular bones as 50% recovery occurs in both abrasion and microfacture samples, significant changes are observed in both subchondral bone and cartilage layer depending on the procedure. The maximum stress levels in the microfractured bone represent approximately a 10.48% increase in cartilage and a 38.25% increase in subchondral bones compared to normal conditions. After 150% recovery, however, all three layers increase their stress levels in microfractured samples. Therefore, the 2D computational analysis results suggest that the microfracture technique should be cautiously used.

In vitro assessment of the trackability of neurovascular intermediate catheters: a comparative analysis

Abstract The advent of new flexible intermediate catheters facilitated manual aspiration thrombectomy (MAT) for treating neurovascular ischaemic diseases. While these catheters are somewhat flexible, most catheters were not designed specifically for aspiration. Trackability is an important property of catheters facilitating catheter advancement in highly tortuous cerebrovasculature. In this study, a novel in vitro trackability test system has been developed using micro pressure transducers and silicone tubes. The exerted force from the catheter tips were quantitatively evaluated while the catheter passed the curved regions. The trackability of three different types of catheters were compared, i.e. Penumbra 054, Concentric DAC 057 and Reverse Reflex. The exerted forces obtained from the first sensor (Sensor 1) during passing the second curve showed the maximum values through the entire transcatheter procedure. When compared, the exerted forces were least for the Penumbra 054 (0.272 ± 0.012 N), representing highly trackable systems in highly tortuous vessel navigation.