Sayyeda M. Hasan

Effects of Isophorone Diisocyanate on the Thermal and Mechanical Properties of Shape-Memory Polyurethane Foams

Previously developed shape-memory polymer foams display fast actuation in water due to plasticization of the polymer network. The actuation presents itself as a depression in the glass-transition temperature when moving from dry to aqueous conditions; this effect limits the working time of the foam to 10 min when used in a transcatheter embolic device. Reproducible foams are developed by altering the chemical backbone, which can achieve working times of greater than 20 min. This is accomplished by incorporating isophorone diisocyanate into the foam, resulting in increased hydrophobicity, glass transitions, and actuation time. This delayed actuation, when compared with previous systems, allows for more optimal working time in clinical applications.

Tungsten-loaded SMP foam nanocomposites with inherent radiopacity and tunable thermo-mechanical properties

Shape memory polymer (SMP) foams have been developed for use in neurovascular occlusion applications. These materials are predominantly polyurethanes that are known for their biocompatibility and tunable properties. However, these polymers inherently lack X-ray visibility, which is a significant challenge for their use as implantable materials. Herein, low density, highly porous shape memory polyurethane foams were developed with tungsten nanoparticles dispersed into the foam matrix, at increasing concentrations, to serve as a radiopaque agent. Utilizing X-ray fluoroscopy sufficient visibility of the foams at small geometries was observed. Thermal characterization of the foams indicated altered thermal response and delayed foam actuation with increasing nanoparticle loading (because of restricted network mobility). Mechanical testing indicated decreased toughness and strength for higher loading because of disruption of the SMP matrix. Overall, filler addition imparted x-ray visibility to the SMP foams and allowed for tuned control of the transition temperature and actuation kinetics for the material.

In vitro and in vivo evaluation of a shape memory polymer foam‐over‐wire embolization device delivered in saccular aneurysm models

Current endovascular therapies for intracranial saccular aneurysms result in high recurrence rates due to poor tissue healing, coil compaction, and aneurysm growth. We propose treatment of saccular aneurysms using shape memory polymer (SMP) foam to improve clinical outcomes. SMP foam-over-wire (FOW) embolization devices were delivered to in vitro and in vivo porcine saccular aneurysm models to evaluate device efficacy, aneurysm occlusion, and acute clotting. FOW devices demonstrated effective delivery and stable implantation in vitro. In vivo porcine aneurysms were successfully occluded using FOW devices with theoretical volume occlusion values greater than 72% and rapid, stable thrombus formation.

Design and verification of a shape memory polymer peripheral occlusion device.

Shape memory polymer foams have been previously investigated for their safety and efficacy in treating a porcine aneurysm model. Their biocompatibility, rapid thrombus formation, and ability for endovascular catheter-based delivery to a variety of vascular beds makes these foams ideal candidates for use in numerous embolic applications, particularly within the peripheral vasculature. This study sought to investigate the material properties, safety, and efficacy of a shape memory polymer peripheral embolization device in vitro. The material characteristics of the device were analyzed to show tunability of the glass transition temperature (Tg) and the expansion rate of the polymer to ensure adequate time to deliver the device through a catheter prior to excessive foam expansion. Mechanical analysis and flow migration studies were performed to ensure minimal risk of vessel perforation and undesired thromboembolism upon device deployment. The efficacy of the device was verified by performing blood flow studies that established affinity for thrombus formation and blood penetration throughout the foam and by delivery of the device in an ultrasound phantom that demonstrated flow stagnation and diversion of flow to collateral pathways.

Modification of shape memory polymer foams using tungsten, aluminum oxide, and silicon dioxide nanoparticles

Shape memory polymer (SMP) foams were synthesized with three different nanoparticles (tungsten, silicon dioxide, and aluminum oxide) for embolization of cerebral aneurysms. Ultra-low density SMP foams have previously been utilized for aneurysm occlusion, resulting in a rapid, stable thrombus. However, the small cross section of foam struts can potentially lead to fracture and particulate generation, which would be a serious adverse event for an embolic device. The goal of this study was to improve the mechanical properties of the system by physically incorporating fillers into the SMP matrix. Thermal and mechanical characterization suggested minimal changes in thermal transition of the SMP nanocomposites and improved mechanical strength and toughness for systems with low filler content. Actuation profiles of the three polymer systems were tuned with filler type and content, resulting in faster SMP foam actuation for nanocomposites containing higher filler content. Additionally, thermal stability of the SMP nanocomposites improved with increasing filler concentration, and particulate count remained well below accepted standard limits for all systems. Extraction studies demonstrated little release of silicon dioxide and aluminum oxide from the bulk over 16 days. Tungstun release increased over the 16 day examination period, with a maximum measured concentration of approxiately 2.87 μg/mL. The SMP nanocomposites developed through this research have the potential for use in medical devices due to their tailorable mechanical properties, thermal resisitivity, and actuation profiles.

Design and biocompatibility of endovascular aneurysm filling devices

The rupture of an intracranial aneurysm, which can result in severe mental disabilities or death, affects approximately 30,000 people in the United States annually. The traditional surgical method of treating these arterial malformations involves a full craniotomy procedure, wherein a clip is placed around the aneurysm neck. In recent decades, research and device development have focused on new endovascular treatment methods to occlude the aneurysm void space. These methods, some of which are currently in clinical use, utilize metal, polymeric, or hybrid devices delivered via catheter to the aneurysm site. In this review, we present several such devices, including those that have been approved for clinical use, and some that are currently in development. We present several design requirements for a successful aneurysm filling device and discuss the success or failure of current and past technologies. We also present novel polymeric-based aneurysm filling methods that are currently being tested in animal models that could result in superior healing.

Particulate Release From Nanoparticle-Loaded Shape Memory Polymer Foams

Highly porous, open-celled shape memory polymer (SMP) foams are being developed for a number of vascular occlusion devices. Applications include abdominal aortic and neurovascular aneurysm or peripheral vascular occlusion. A major concern with implanting these high surface area materials in the vasculature is the potential to generate unacceptable particulate burden, in terms of number, size, and composition. This study demonstrates that particulate numbers and sizes in SMP foams are in compliance with limits stated by the most relevant standard and guidance documents. Particulates were quantified in SMP foams as made, postreticulation, and after incorporating nanoparticles intended to increase material toughness and improve radiopacity. When concentrated particulate treatments were administered to fibroblasts, they exhibited high cell viability (100%). These results demonstrate that the SMP foams do not induce an unacceptable level of risk to potential vascular occlusion devices due to particulate generation.

Cold Plasma Reticulation of Shape Memory Embolic Tissue Scaffolds

Polyurethane shape memory polymer (SMP) foams are proposed for use as thrombogenic scaffolds to improve the treatment of vascular defects, such as cerebral aneurysms. However, gas blown SMP foams inherently have membranes between pores, which can limit their performance as embolic tissue scaffolds. Reticulation, or the removal of membranes between adjacent foam pores, is advantageous for improving device performance by increasing blood permeability and cellular infiltration. This work characterizes the effects of cold gas plasma reticulation processes on bulk polyurethane SMP films and foams. Plasma-induced changes on material properties are characterized using scanning electron microscopy, uniaxial tensile testing, goniometry, and free strain recovery experiments. Device specific performance is characterized in terms of permeability, platelet attachment, and cell-material interactions. Overall, plasma reticulated SMP scaffolds show promise as embolic tissue scaffolds due to increased bulk permeability, retained thrombogenicity, and favorable cell-material interactions.

Development of siloxane-based amphiphiles as cell stabilizers for porous shape memory polymer systems

HYPOTHESIS Polyurethane foaming surfactants are cell stabilized at the polymer-gas interface during foam blowing to prevent bubble coalescence. Siloxane-based surfactants are typically used to generate a surface tension gradient at the interface. The chemical structure of the hydrophobic and hydrophilic units affects surfactant properties, which can further influence foam morphology. EXPERIMENTS Siloxane-polyethylene glycol (PEG) ether amphiphiles were synthesized in high yield via hydrosilylation to serve as surfactants for shape memory polymer (SMP) foams. Hydrophobic units consisted of trisiloxane and polydimethyl siloxane, and PEG allyl methyl ether (n=8 or 25) was the hydrophilic component. Upon confirming successful synthesis of the surfactants, their surface tension was measured to study their suitability for use in foaming. SMP foams were synthesized using the four surfactants, and the effects of surfactant structure and concentration on foam morphology were evaluated. FINDINGS Spectroscopic data confirmed successful siloxane-PEG coupling. All surfactants had a low surface tension of 20-21mN/m, indicating their ability to reduce interfacial tension. SMP foams were successfully fabricated with tunable cell size and morphology as a function of surfactant type and concentration.

Embolic applications of shape memory polyurethane scaffolds

Polyurethane shape memory polymers (SMPs) have found a variety of uses in the medical industry in the form of self-tightening sutures, suture anchors, ligament fixation devices, vascular stents, and thrombectomy devices. New formulations of polyurethane SMP scaffolds are gaining significant interest for use in vascular embolization procedures. These scaffolds have demonstrated rapid time to occlusion, improved healing, and favorable biocompatibility, and they eliminate the need to implant multiple devices to achieve stable occlusion, significantly reducing procedure times and the total cost of treatment. Described here are various methods used to fabricate SMP scaffolds, indications for SMP scaffold embolization, advantages of using these scaffolds in embolization procedures, results seen in animal studies that made use of SMP scaffolds, and future directions for SMP scaffolds that will propel the technology to significant use beyond vessel occlusion.