Custom 3D Printable Silicones with Tunable Stiffness.

Silicone elastomers have broad versatility within a variety of potential advanced materials applications, such as soft robotics, biomedical devices, and metamaterials. A series of custom 3D printable silicone inks with tunable stiffness is developed, formulated, and characterized. The silicone inks exhibit excellent rheological behavior for 3D printing, as observed from the printing of porous structures with controlled architectures. Herein, the capability to tune the stiffness of printable silicone materials via careful control over the chemistry, network formation, and crosslink density of the ink formulations in order to overcome the challenging interplay between ink development, post-processing, material properties, and performance is demonstrated.

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.

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.

Low density biodegradable shape memory polyurethane foams for embolic biomedical applications.

Low density shape memory polymer foams hold significant interest in the biomaterials community for their potential use in minimally invasive embolic biomedical applications. The unique shape memory behavior of these foams allows them to be compressed to a miniaturized form, which can be delivered to an anatomical site via a transcatheter process and thereafter actuated to embolize the desired area. Previous work in this field has described the use of a highly covalently crosslinked polymer structure for maintaining excellent mechanical and shape memory properties at the application-specific ultralow densities. This work is aimed at further expanding the utility of these biomaterials, as implantable low density shape memory polymer foams, by introducing controlled biodegradability. A highly covalently crosslinked network structure was maintained by use of low molecular weight, symmetrical and polyfunctional hydroxyl monomers such as polycaprolactone triol (PCL-t, Mn= 900 g), N,N,N0,N0-tetrakis(hydroxypropyl)ethylenediamine and tris(2-hydroxyethyl)amine. Control over the degradation rate of the materials was achieved by changing the concentration of the degradable PCL-t monomer and by varying the material hydrophobicity. These porous SMP materials exhibit a uniform cell morphology and excellent shape recovery, along with controllable actuation temperature and degradation rate. We believe that they form a new class of low density biodegradable SMP scaffolds that can potentially be used as "smart" non-permanent implants in multiple minimally invasive biomedical applications.

Porous Shape Memory Polymers.

Porous shape memory polymers (SMPs) include foams, scaffolds, meshes, and other polymeric substrates that possess porous three-dimensional macrostructures. Porous SMPs exhibit active structural and volumetric transformations and have driven investigations in fields ranging from biomedical engineering to aerospace engineering to the clothing industry. The present review article examines recent developments in porous SMPs, with focus given to structural and chemical classification, methods of characterization, and applications. We conclude that the current body of literature presents porous SMPs as highly interesting smart materials with potential for industrial use.

Controlling the Actuation Rate of Low-Density Shape-Memory Polymer Foams in Water.

SMPs have been shown to actuate below their dry glass transition temperatures in the presence of moisture due to plasticization. This behavior has been proposed as a self-actuating mechanism of SMPs in water/physiological media. However, control over the SMP actuation rate, a critical factor for in vivo transcatheter device delivery applications, has not been previously reported. Here, a series of polyurethane SMPs with systematically varied hydrophobicity is described that permits control of the time for their complete shape recovery in water from under 2 min to more than 24 h. This control over the SMP actuation rate can potentially provide significant improvement in their delivery under conditions, which may expose them to high-moisture environments prior to actuation.

Moisture desorption rates from TATB formulations: experiments and kinetic models.

The rate of water desorption from PBX-9502, a formulation containing 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), is measured using temperature-programmed desorption and modeled using conventional kinetic modeling methods. The results of these studies show two stages of moisture release. At lower temperatures, the release is likely assisted by thermal expansion of the TATB and melting of the Kel-F binder. At higher temperatures, a considerable amount of water is released and is attributed to sublimation of the TATB, which exposes new surfaces for water desorption.

Ultra Low Density and Highly Crosslinked Biocompatible Shape Memory Polyurethane Foams.

We report the development of highly chemically crosslinked, ultra low density (~0.015 g/cc) polyurethane shape memory foams synthesized from symmetrical, low molecular weight and branched hydroxyl monomers. Sharp single glass transitions (Tg) customizable in the functional range of 45-70 °C were achieved. Thermomechanical testing confirmed shape memory behavior with 97-98% shape recovery over repeated cycles, a glassy storage modulus of 200-300 kPa and recovery stresses of 5-15 kPa. Shape holding tests under constrained storage above the Tg showed stable shape memory. A high volume expansion of up to 70 times was seen on actuation of these foams from a fully compressed state. Low in-vitro cell activation induced by the foam compared to controls demonstrates low acute bio-reactivity. We believe these porous polymeric scaffolds constitute an important class of novel smart biomaterials with multiple potential applications.

Biomedical applications of thermally activated shape memory polymers.

Shape memory polymers (SMPs) are smart materials that can remember a primary shape and can return to this primary shape from a deformed secondary shape when given an appropriate stimulus. This property allows them to be delivered in a compact form via minimally invasive surgeries in humans, and deployed to achieve complex final shapes. Here we review the various biomedical applications of SMPs and the challenges they face with respect to actuation and biocompatibility. While shape memory behavior has been demonstrated with heat, light and chemical environment, here we focus our discussion on thermally stimulated SMPs.

Magnetic resonance flow velocity and temperature mapping of a shape memory polymer foam device.

BACKGROUND: Interventional medical devices based on thermally responsive shape memory polymer (SMP) are under development to treat stroke victims. The goals of these catheter-delivered devices include re-establishing blood flow in occluded arteries and preventing aneurysm rupture. Because these devices alter the hemodynamics and dissipate thermal energy during the therapeutic procedure, a first step in the device development process is to investigate fluid velocity and temperature changes following device deployment. METHODS: A laser-heated SMP foam device was deployed in a simplified in vitro vascular model. Magnetic resonance imaging (MRI) techniques were used to assess the fluid dynamics and thermal changes associated with device deployment. RESULTS: Spatial maps of the steady-state fluid velocity and temperature change inside and outside the laser-heated SMP foam device were acquired. CONCLUSIONS: Though non-physiological conditions were used in this initial study, the utility of MRI in the development of a thermally-activated SMP foam device has been demonstrated.

Thermomechanical properties, collapse pressure, and expansion of shape memory polymer neurovascular stent prototypes.

Shape memory polymer stent prototypes were fabricated from thermoplastic polyurethane. Commercial stents are generally made of stainless steel or other alloys. These alloys are too stiff and prevent most stent designs from being able to navigate small and tortuous vessels to reach intracranial lesions. A solid tubular model and a high flexibility laser etched model are presented. The stents were tested for collapse in a pressure chamber. At 37 degrees C, the full collapse pressure was comparable to that of commercially available stents, and higher than the estimated maximum pressure exerted by intracranial arteries. However, there is a potential for onset of collapse, which needs further study. The stents were crimped and expanded, the laser-etched stent showed full recovery with an expansion ratio of 2.7 and a 1% axial shortening.

Fabrication and characterization of cylindrical light diffusers comprised of shape memory polymer.

We developed a technique for constructing light diffusing devices comprised of a flexible shape memory polymer (SMP) cylindrical diffuser attached to the tip of an optical fiber. The devices are fabricated by casting an SMP rod over the cleaved tip of an optical fiber and media blasting the SMP rod to create a light diffusing surface. The axial and polar emission profiles and circumferential (azimuthal) uniformity are characterized for various blasting pressures, nozzle-to-sample distances, and nozzle translation speeds. The diffusers are generally strongly forward-directed and consistently withstand over 8 W of incident IR laser light without suffering damage when immersed in water. These devices are suitable for various endoluminal and interstitial biomedical applications.

Fabrication and in vitro deployment of a laser-activated shape memory polymer vascular stent.

BACKGROUND: Vascular stents are small tubular scaffolds used in the treatment of arterial stenosis (narrowing of the vessel). Most vascular stents are metallic and are deployed either by balloon expansion or by self-expansion. A shape memory polymer (SMP) stent may enhance flexibility, compliance, and drug elution compared to its current metallic counterparts. The purpose of this study was to describe the fabrication of a laser-activated SMP stent and demonstrate photothermal expansion of the stent in an in vitro artery model. METHODS: A novel SMP stent was fabricated from thermoplastic polyurethane. A solid SMP tube formed by dip coating a stainless steel pin was laser-etched to create the mesh pattern of the finished stent. The stent was crimped over a fiber-optic cylindrical light diffuser coupled to an infrared diode laser. Photothermal actuation of the stent was performed in a water-filled mock artery. RESULTS: At a physiological flow rate, the stent did not fully expand at the maximum laser power (8.6 W) due to convective cooling. However, under zero flow, simulating the technique of endovascular flow occlusion, complete laser actuation was achieved in the mock artery at a laser power of ~8 W. CONCLUSION: We have shown the design and fabrication of an SMP stent and a means of light delivery for photothermal actuation. Though further studies are required to optimize the device and assess thermal tissue damage, photothermal actuation of the SMP stent was demonstrated.

Prototype fabrication and preliminary in vitro testing of a shape memory endovascular thrombectomy device.

An electromechanical microactuator comprised of shape memory polymer (SMP) and shape memory nickel-titanium alloy (nitinol) was developed and used in an endovascular thrombectomy device prototype. The microactuator maintains a straight rod shape until an applied current induces electro-resistive (Joule) heating, causing the microactuator to transform into a corkscrew shape. The straight-to-corkscrew transformation geometry was chosen to permit endovascular delivery through (straight form) and retrieval of (corkscrew form) a stroke-causing thrombus (blood clot) in the brain. Thermal imaging of the microactuator during actuation in air indicated that the steady-state temperature rise caused by Joule heating varied quadratically with applied current and that actuation occurred near the glass transition temperature of the SMP (86 degrees C). To demonstrate clinical application, the device was used to retrieve a blood clot in a water-filled silicone neurovascular model. Numerical modeling of the heat transfer to the surrounding blood and associated thermal effects on the adjacent artery potentially encountered during clinical use suggested that any thermal damage would likely be confined to localized areas where the microactuator was touching the artery wall. This shape memory mechanical thrombectomy device is a promising tool for treating ischemic stroke without the need for infusion of clot-dissolving drugs.

A shape memory polymer dialysis needle adapter for the reduction of hemodynamic stress within arteriovenous grafts.

A deployable, shape memory polymer adapter is investigated for reducing the hemodynamic stress caused by dialysis needle flow impingement within an arteriovenous graft. Computational fluid dynamics simulations of dialysis sessions with and without the adapter demonstrate that the adapter provides a significant decrease in the wall shear stress. Preliminary in vitro flow visualization measurements are made within a graft model following delivery and actuation of a prototype shape memory polymer adapter. Both the simulations and the qualitative flow visualization measurements demonstrate that the adapter reduces the severity of the dialysis needle flow impingement on the vascular access graft.

Prototype laser-activated shape memory polymer foam device for embolic treatment of aneurysms.

Conventional embolization of cerebral aneurysms using detachable coils is time-consuming and often requires retreatment. These drawbacks have prompted the development of new methods of aneurysm occlusion. We present the fabrication and laser deployment of a shape memory (SMP) polymer expanding foam device. Data acquired in an in vitro basilar aneurysm model with and without flow showed successful treatment, with the flow rate affecting foam expansion and the temperature at the aneurysm wall.

Shape memory polymer stent with expandable foam: a new concept for endovascular embolization of fusiform aneurysms.

We demonstrate a new concept for endovascular embolization of nonnecked fusiform aneurysms. A device prototype consisting of a stent augmented with expandable foam, both made from shape memory polymer, was fabricated and deployed in an in vitro model. Visual observation indicated that the foam achieved embolization of the aneurysm while the stent maintained an open lumen in the parent artery. The shape memory polymer stent-foam device is a potential tool for treatment of nonnecked fusiform aneurysms, as well as an alternative to stent- and balloon-assisted coil embolization of wide-necked aneurysms.

Inductively heated shape memory polymer for the magnetic actuation of medical devices.

Presently, there is interest in making medical devices such as expandable stents and intravascular microactuators from shape memory polymer (SMP). One of the key challenges in realizing SMP medical devices is the implementation of a safe and effective method of thermally actuating various device geometries in vivo. A novel scheme of actuation by Curie-thermoregulated inductive heating is presented. Prototype medical devices made from SMP loaded with nickel zinc ferrite ferromagnetic particles were actuated in air by applying an alternating magnetic field to induce heating. Dynamic mechanical thermal analysis was performed on both the particle-loaded and neat SMP materials to assess the impact of the ferrite particles on the mechanical properties of the samples. Calorimetry was used to quantify the rate of heat generation as a function of particle size and volumetric loading of ferrite particles in the SMP. These tests demonstrated the feasibility of SMP actuation by inductive heating. Rapid and uniform heating was achieved in complex device geometries and particle loading up to 10% volume content did not interfere with the shape recovery of the SMP.

Anastomotic vessels remain viable after photodynamic therapy in primate models of choroidal neovascularization.

PURPOSE: Anastomotic vessels in exudative age-related macular degeneration (AMD) represent a serious clinical feature that reportedly does not respond well to either photocoagulation or photodynamic therapy (PDT). Anastomoses also occur in various animal models of choroidal neovascularization (CNV). In the present study, anastomotic vessels and their patency were evaluated in two primate CNV laser-trauma models after PDT, by using two novel photosensitizers. METHODS: In cynomolgus (Macaca fascicularis) and squirrel (Saimiri sciureus) monkey eyes (n = 20), matrix placement of laser photocoagulation sites elicited CNV as a component of the development of fibrovascular tissue (FVT). FVT sites received PDT according to specific drug infusion and laser light treatment parameters. FVTs and anastomoses were evaluated by fundus photography, fluorescein angiography, and histologic examination. RESULTS: Anastomoses averaged approximately 48% of FVT sites, with greatest occurrence in the macaque. Although PDT with each photosensitizer effectively produced FVT closure, both retinal vessels and anastomoses remained patent. CONCLUSIONS: Although PDT is effective in closing the choroidal neovascularization in FVT, this technique was ineffective in occluding anastomotic vessels and their associated tributaries within the mid- to proximal retina. Various factors (vascular diameter, composition, blood flow, orientation) may contribute to continued anastomotic patency. By convention, such vessels would typically be defined as chorioretinal anastomoses (CRAs); however, continuing studies suggest the possibility that these neovessels constitute dual-origin hybrids. Regardless of origin, viable anastomoses provide one potential mechanism for revascularization to occur after PDT and may help to explain why CRAs are considered a poor prognostic sign in patients with AMD.

Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

PURPOSE: To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus). METHODS: PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes. RESULTS: Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography. CONCLUSION: PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.