Shape Memory Polymer Foams Synthesized Using Glycerol and Hexanetriol for Enhanced Degradation Resistance.

Shape memory polymer foams have been used in a wide range of medical applications, including, but not limited to, vessel occlusion and aneurysm treatment. This unique polymer system has been proven to shape-fill a void, which makes it useful for occlusion applications. While the shape memory polymer foam has superior performance and healing outcomes compared to its leading competitors, some device applications may benefit from longer material degradation times, or degradation-resistant formulations with increased fibrous encapsulation. In this study, biostable shape memory polymer foams were synthesized, and their physical and chemical properties were characterized as an initial evaluation of feasibility for vascular occlusion applications. After characterizing their shape memory behavior in an aqueous environment, degradation of this polymer system was studied in vitro using accelerated oxidative and hydrolytic solutions. Results indicated that the foams did not lose mass under oxidative or hydrolytic conditions, and they maintained high shape recovery in aqueous in vitro models. These degradation-resistant systems have potential for use in vascular occlusion and other wound healing applications that benefit from permanent, space-filling shape memory behavior.

Comparative mechanics of diverse mammalian carotid arteries.

The prevalence of diverse animal models as surrogates for human vascular pathologies necessitate a comprehensive understanding of the differences that exist between species. Comparative passive mechanics are presented here for the common carotid arteries taken from bovine, porcine, ovine, leporine, murine-rat, and murine-mouse specimens. Data is generated using a scalable biaxial mechanical testing device following consistent circumferential (pressure-diameter) and axial (force-length) testing protocols. The structural mechanical response of carotids under equivalent loading, quantified by the deformed inner radius, deformed wall thickness, lumen area compliance and axial force, varies significantly among species but generally follows allometric scaling. Conversely, descriptors of the local mechanical response within the deformed arterial wall, including mean circumferential stress, mid-wall circumferential stretch, and mean axial stress, are relatively consistent across species. Unlike the larger animals studied, the diameter distensibility curves of murine specimens are non-monotonic and have a significantly higher value at 100 mmHg. Taken together, our results provide baseline structural and mechanical information for carotid arteries across a broad range of common animal models.

In vitro performance of a shape memory polymer foam-coated coil embolization device.

Intracranial saccular aneurysm treatment using endovascular embolization devices are limited by aneurysm recurrence that can lead to aneurysm rupture. A shape memory polymer (SMP) foam-coated coil (FCC) embolization device was designed to increase packing density and improve tissue healing compared to current commercial devices. FCC devices were fabricated and tested using in vitro models to assess feasibility for clinical treatment of intracranial saccular aneurysms. FCC devices demonstrated smooth delivery through tortuous pathways similar to control devices as well as greater than 10 min working time for clinical repositioning during deployment. Furthermore, the devices passed pilot verification tests for particulates, chemical leachables, and cytocompatibility. Finally, devices were successfully implanted in an in vitro saccular aneurysm model with large packing density. Though improvements and future studies evaluating device stiffness were identified as a necessity, the FCC device demonstrates effective delivery and packing performance that provides great promise for clinical application of the device in treatment of intracranial saccular aneurysms.

An experimental canine patent ductus arteriosus occlusion device based on shape memory polymer foam in a nitinol cage.

Patent ductus arteriosus (PDA) is a congenital cardiovascular defect in which a fetal connection between the aorta and pulmonary artery does not spontaneously close shortly after birth. If left uncorrected serious complications and even death can occur. Surgical ligation is the traditional treatment method; however, it is an invasive procedure, that motivates development of a minimally invasive option. Shape memory polymer (SMP) foams are unique materials that hold promise in the field of minimally invasive occlusion devices. In this work, a prototype nitinol foam cage (NFC) incorporating SMP foams has been designed and evaluated in multiple mechanical and in vitro verification tests. The NFC demonstrated acceptable fatigue resistance in a preliminary strut integrity test, withstanding one million cycles without complete strut fracture. Radial force analysis of both thick- and thin-walled prototype variations generated less vessel distension and wall tension in a vessel mimic compared to a commercial device. The NFCs exhibited negligible in vitro migration, comparable to that of a commercial device, using simplified, ideal models of PDA. Deployment characteristics of the prototypes were evaluated and compared to that of a commercial device when delivered into physiological models of PDA. During mock deployments, a veterinary cardiologist noted that, while deliverable, the thin-walled NFC prototype exhibited poor deployment characteristics, however the thick-walled NFC had deployment characteristics comparable to that of a commercial device. The promising results of this study warrant further investigation of the NFC device for canine PDA closure.

Mechanical and in vitro evaluation of an experimental canine patent ductus arteriosus occlusion device.

Patent ductus arteriosus (PDA) is a congenital cardiovascular malformation in which a fetal connection between the aorta and pulmonary artery remains patent after birth. This defect commonly results in clinical complications, even death, necessitating closure. Surgical ligation is the most common treatment but requires a thoracotomy and is therefore invasive. A minimally invasive option is preferable. A prototype device for PDA occlusion which utilizes shape memory polymer foams has been developed and evaluated using mechanical and in vitro experiments. Removal force and radial pressure measurements show that the prototype device exhibited a lower removal force and radial pressure than a commercially available device. The in vitro experiments conducted within simplified and physiological PDA models showed that the prototype does not migrate out of position into the pulmonary artery at either physiological or elevated pressures in multiple model configurations. While the radial pressure and removal force were lower than commercial devices, the device performed acceptably in the in vitro benchtop experiments warranting further prototype development.

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. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1407-1415, 2016.

A Processable Shape Memory Polymer System for Biomedical Applications.

Polyurethane shape memory polymers (SMPs) with tunable thermomechanical properties and advanced processing capabilities are synthesized, characterized, and implemented in the design of a microactuator medical device prototype. The ability to manipulate glass transition temperature (Tg ) and crosslink density in low-molecular weight aliphatic thermoplastic polyurethane SMPs is demonstrated using a synthetic approach that employs UV catalyzed thiol-ene "click" reactions to achieve postpolymerization crosslinking. Polyurethanes containing varying C=C functionalization are synthesized, solution blended with polythiol crosslinking agents and photoinitiator and subjected to UV irradiation, and the effects of number of synthetic parameters on crosslink density are reported. Thermomechanical properties are highly tunable, including glass transitions tailorable between 30 and 105 °C and rubbery moduli tailorable between 0.4 and 20 MPa. This new SMP system exhibits high toughness for many formulations, especially in the case of low crosslink density materials, for which toughness exceeds 90 MJ m(-3) at select straining temperatures. To demonstrate the advanced processing capability and synthetic versatility of this new SMP system, a laser-actuated SMP microgripper device for minimally invasive delivery of endovascular devices is fabricated, shown to exhibit an average gripping force of 1.43 ± 0.37 N and successfully deployed in an in vitro experimental setup under simulated physiological conditions.

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.