Landon D. Nash

A pH-responsive supramolecular polymer gel as an enteric elastomer for use in gastric devices

Devices resident in the stomach -- which are used for a variety of clinical applications including nutritional modulation for bariatrics, ingestible electronics for diagnosis and monitoring, and gastric retentive dosage forms for prolonged drug delivery -- typically incorporate elastic polymers to compress the devices during delivery through the esophagus and other narrow orifices in the digestive system. However, in the event of accidental device fracture or migration, the non-degradable nature of these materials risks intestinal obstruction. Here, we show that an elastic, pH-responsive supramolecular gel remains stable and elastic in the acidic environment of the stomach but can be dissolved in the neutral-pH environment of the small and large intestines. In a large animal model, prototype devices with these materials as the key component demonstrated prolonged gastric retention and safe passage. These enteric elastomers should increase the safety profile for a wide range of gastric retentive devices.

A High‐Performance Recycling Solution for Polystyrene Achieved by the Synthesis of Renewable Poly(thioether) Networks Derived from d‐Limonene

Nanocomposite polymers are prepared using a new sustainable materials synthesis process in which d-Limonene functions simultaneously both as a solvent for recycling polystyrene (PS) waste and as a monomer that undergoes UV-catalyzed thiol-ene polymerization reactions with polythiol comonomers to afford polymeric products composed of precipitated PS phases dispersed throughout elastomeric poly(thioether) networks. These blended networks exhibit mechanical properties that greatly exceed those of either polystyrene or the poly(thioether) network homopolymers alone.

Reticulation of low density shape memory polymer foam with an in vivo demonstration of vascular occlusion

Predominantly closed-cell low density shape memory polymer (SMP) foam was recently reported to be an effective aneurysm filling device in a porcine model (Rodriguez et al., Journal of Biomedical Materials Research Part A 2013: (http://dx.doi.org/10.1002/jbm.a.34782)). Because healing involves blood clotting and cell migration throughout the foam volume, a more open-cell structure may further enhance the healing response. This research sought to develop a non-destructive reticulation process for this SMP foam to disrupt the membranes between pore cells. Non-destructive mechanical reticulation was achieved using a gravity-driven floating nitinol pin array coupled with vibratory agitation of the foam and supplemental chemical etching. Reticulation resulted in a reduced elastic modulus and increased permeability, but did not impede the shape memory behavior. Reticulated foams were capable of achieving rapid vascular occlusion in an in vivo porcine model.

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.

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.

Increased X-ray Visualization of Shape Memory Polymer Foams by Chemical Incorporation of Iodine Motifs

Shape memory polymers can be programmed into a secondary geometry and recovered to their primary geometry with the application of a controlled stimulus. Porous shape memory polymer foam scaffolds that respond to body temperature show particular promise for embolic medical applications. A limitation for the minimally invasive delivery of these materials is an inherent lack of X-ray contrast. In this work, a triiodobenzene containing a monomer was incorporated into a shape memory polymer foam material system to chemically impart X-ray visibility and increase material toughness. Composition and process changes enabled further control over material density and thermomechanical properties. The proposed material system demonstrates a wide range of tailorable functional properties for the design of embolic medical devices, including X-ray visibility, expansion rate, and porosity. Enhanced visualization of these materials can improve the acute performance of medical devices used to treat vascular malformations, and the material porosity provides a healing scaffold for durable occlusion.

Characterization of plasma deposited hydrocarbon diffusion barriers for embolic foam devices

Shape memory polymer (SMP) containing medical implants that are delivered through catheters require controlled expansion times to prevent the device from binding in the delivery catheter. Delayed expansion can be accomplished using body temperature and moisture plasticization from the aqueous environment of the blood. Although bulk material approaches are effective at delaying the expansion rate, they often compromise the ultimate expansion volume, or necessitate temperatures above body temperature for actuation. These factors motivate material refinement beyond bulk chemistry changes to achieve nonlinear passive actuation profiles. In this work, plasma deposited hydrocarbon diffusion barriers enable a second degree of material expansion control, facilitating extended catheter delivery times for endovascular medical devices. Hydrocarbon plasma films polymerized from mixtures of acetylene, ethylene and propylene were deposited on silicon wafers and characterized using ellipsometry, static water contact angles, and x-ray photoelectron spectroscopy. Selected plasma processes were applied to polyurethane SMP foams and material performance was characterized using differential scanning calorimetry and unconstrained foam expansion in 37 °C water. These plasma films were found to increase surface hydrophobicity and delay the moisture plasticization rate of shape memory polymer embolic foams without altering bulk thermo-mechanical properties.

Fabrication and Characterization of Optical Tissue Phantoms Containing Macrostructure

The rapid development of new optical imaging techniques is dependent on the availability of low-cost, customizable, and easily reproducible standards. By replicating the imaging environment, costly animal experiments to validate a technique may be circumvented. Predicting and optimizing the performance of in vivo and ex vivo imaging techniques requires testing on samples that are optically similar to tissues of interest. Tissue-mimicking optical phantoms provide a standard for evaluation, characterization, or calibration of an optical system. Homogenous polymer optical tissue phantoms are widely used to mimic the optical properties of a specific tissue type within a narrow spectral range. Layered tissues, such as the epidermis and dermis, can be mimicked by simply stacking these homogenous slab phantoms. However, many in vivo imaging techniques are applied to more spatially complex tissue where three dimensional structures, such as blood vessels, airways, or tissue defects, can affect the performance of the imaging system. This protocol describes the fabrication of a tissue-mimicking phantom that incorporates three-dimensional structural complexity using material with optical properties of tissue. Look-up tables provide India ink and titanium dioxide recipes for optical absorption and scattering targets. Methods to characterize and tune the material optical properties are described. The phantom fabrication detailed in this article has an internal branching mock airway void; however, the technique can be broadly applied to other tissue or organ structures.

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.

Effects of Sterilization on Shape Memory Polyurethane Embolic Foam Devices

Polyurethane shape memory polymer (SMP) foams have been developed for various embolic medical devices due to their unique properties in minimally invasive biomedical applications. These polyurethane materials can be stored in a secondary shape, from which they can recover their primary shape after exposure to an external stimulus, such as heat and water exposure. Tailored actuation temperatures of SMPs provide benefits for minimally invasive biomedical applications, but incur significant challenges for SMP-based medical device sterilization. Most sterilization methods require high temperatures or high humidity to effectively reduce the bioburden of the device, but the environment must be tightly controlled after device fabrication. Here, two probable sterilization methods (nontraditional ethylene oxide (ntEtO) gas sterilization and electron beam irradiation) are investigated for SMP medical devices. Thermal characterization of the sterilized foams indicated that ntEtO gas sterilization significantly decreased the glass transition temperature. Further material characterization was undertaken on the electron beam (ebeam) sterilized samples, which indicated minimal changes to the thermomechanical integrity of the bulk foam and to the device functionality.