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Direct ink writing of silicone elastomers enables printing with precise control of porosity and mechanical properties of ordered cellular solids, suitable for shock absorption and stress mitigation applications. With the ability to manipulate structure and feedstock stiffness, the design space becomes challenging to parse to obtain a solution producing a desired mechanical response. Here, we derive an analytical design approach for a specific architecture. Results from finite element simulations and quasi-static mechanical tests of two different parallel strand architectures were analyzed to understand the structure-property relationships under uniaxial compression. Combining effective stiffness-density scaling with least squares optimization of the stress responses yielded general response curves parameterized by resin modulus and strand spacing. An analytical expression of these curves serves as a reduced order model, which, when optimized, provides a rapid design capability for filament-based 3D printed structures. As a demonstration, the optimal design of a face-centered tetragonal architecture is computed that satisfies prescribed minimum and maximum load constraints.

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.

Aim: The new photosensitiser PhotoPoint MV6401, indium chloride methyl pyropheophorbide, was assessed as a possible ocular photodynamic therapy agent in a rat model of experimentally induced corneal neovascularisation and in choriocapillaris closure in the rabbit. Optimal drug and light activation parameters were determined. Methods: MV6401 (Miravant Pharmaceuticals, Inc, Santa Barbara, CA, USA) was activated at 664 nm using a DD3-0665 (Miravant Systems Inc) 0.5 W diode laser. Corneal neovascularisation in rats was induced using an N-heptanol technique. The evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.01–0.1 μmol/kg, 5–25 J/cm2, and 10–60 minutes, respectively. The efficacy of MV6401 on normal choriocapillaris and choroidal vessels was evaluated in rabbits with indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. In rabbits, the evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.025–0.25 μmol/kg, 3.3–20 J/cm2, and 10 minutes, respectively. Results: In the rat corneal neovascularisation model, an optimal intravenous drug dosage of 0.075 μmol/kg was activated by a 20 J/cm2 light dose at 10 minutes after drug administration, the results of which demonstrated early evidence of efficacy in ocular neovascularisation. In rabbits, closure of the normal choriocapillaris was selectively achieved at a drug dosage of 0.15 μmol/kg using light doses from 3.3 to 20 J/cm2. Conclusion: PhotoPoint MV6401 is a potent photosensitiser that demonstrates both efficacy and selectivity in experimental ocular models.

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.

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.

A preliminary single-animal study of in vivo argon laser vascular welding was conducted using a canine model. The effects of temperature feedback control and saline drip cooling on patency and collagen cross-linking were investigated. The surface temperature at the centre of the laser spot was monitored using a two-colour infrared thermometer. The surface temperature was limited by either a saline drip or feedback control of the laser. Acute patency was evaluated and collagen cross-link assays were performed. Though both protocols yielded successful tissue fusion, welds maintained at a surface temperature of 50°C using feedback control had an elevated cross-link count compared to controls, whereas tissues irradiated without feedback control experienced a cross-link decrease. Simulations using the LATIS (LAser-TISsue) computer code suggest that drip-cooled procedures achieve significantly higher temperatures beneath the tissue surface than temperature feedback-controlled procedures. Differences between the volumetric heating associated with drip-cooled and feedback-controlled protocols may account for the different effects on collagen cross-links. Covalent mechanisms may play a role in argon laser vascular fusion.

Plasma mediated ablation of collagen gels and porcine cornea was studied at various laser pulse durations in the range of 1 ns-300 fs at 1053-nm wavelength. It was found that pulsed laser ablation of transparent and weakly absorbing gels is always mediated by plasma. On the other hand, ablation of strongly absorbing tissues is mediated by plasma in the ultrashort-pulse range only. Ablation threshold along with plasma optical breakdown threshold decreases with increasing tissue absorbance for subnanosecond pulses. In contrast, the ablation threshold was found to be practically independent of tissue linear absorption for femtosecond laser pulses. The mechanism of optical breakdown at the tissue surface was theoretically investigated. In the nanosecond range of laser pulse duration, optical breakdown proceeds via avalanche ionization initiated by heating of electrons contributed by strongly absorbing impurities at the tissue surface. In the ultrashortpulse range, optical breakdown is initiated by multiphoton ionization of the irradiated medium (six photons in case of tissue irradiated at 1053-nm wavelength), and is less sensitive to linear absorption. High-quality ablation craters with no thermal or mechanical damage to surrounding material were obtained with subpicosecond laser pulses. Experimental results suggest that subpicosecond plasma mediated ablation can be employed as a tool for precise laser microsurgery of various tissues.

A blood clot (thrombus) that becomes lodged in the arterial network supplying the brain can cause an ischemic stroke, depriving the brain of oxygen and often resulting in permanent disability. As an alternative to conventional clot-dissolving drug treatment, we are developing an intravascular laser-activated therapeutic device using shape memory polymer (SMP) to mechanically retrieve the thrombus and restore blood flow to the brain. Thermal imaging and computer simulation were used to characterize the optical and photothermal behavior of the SMP microactuator. Deployment of the SMP device in an in vitro thrombotic vascular occlusion model demonstrated the clinical treatment concept.

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.

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.

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.

A majority of patients who suffer hemorrhaging as a result of a ruptured cerebral aneurysm experience reduced quality of life, long term brain damage, or death. Improved understanding of the flow patterns in cerebral aneurysms will lead to better techniques for their detection and treatment. Experiments are conducted in a generic flow phantom to characterize the basic behavior of blood flow in basilar saccular aneurysms. The test setup models a saccular aneurysm that forms at the bifurcation of the basilar artery into the Circle of Willis. Three input flow conditions are tested: a physiological flow waveform obtained from Kato (2002) [1] and two steady flow conditions corresponding to the peak and mean flow rates of the physiological flow waveform. Steady cases are examined to study the effect of increasing Reynolds number on the flow and the pulsatile case to quantify unsteady effects. The results reveal highly three dimensional flow patterns within the aneurysm. Velocity and vorticity fluctuations are extracted to investigate the nature of the unsteady flows. Wall shear stress is estimated around the aneurysm dome to examine its role in wall weakening and failure.Copyright © 2006 by ASME

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.

Plasma mediated ablation of collagen gels and porcine cornea was studied at various laser pulse durations in the range from 350 fs to 1 ns at 1053 nm wavelength. A time resolved stress detection technique was employed to measure transient stress profiles and amplitudes. Optical microscopy was used to characterize ablation craters qualitatively, while a wide band acoustic transducer helped to quantify tissue mechanical response and the ablation threshold. The ablation threshold was measured as a function of laser pulse duration and linear absorption coefficient. For nanosecond pulses the ablation threshold was found to have a strong dependence on the linear absorption coefficient of the material. As the pulse length decreased into the subpicosecond regime the ablation threshold became insensitive to the linear absorption coefficient. High quality ablation craters with no thermal or mechanical damage to surrounding material were obtained with 350 fs laser pulses. The mechanism of optical breakdown at the tissue surface was theoretically investigated. In the nanosecond regime, optical breakdown proceeds as an electron collisional avalanche ionization initiated by thermal seed electrons. These seed electrons are created by heating of the tissue by linear absorption. In the ultrashort pulse range, optical breakdown is initiated by the multiphoton ionization of the irradiated medium (6 photons in case of tissue irradiated at 1053 nm wavelength), and becomes less sensitive to the linear absorption coefficient. The energy deposition profile is insensitive to both the laser pulse duration and the linear absorption coefficient.

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.

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.

Purpose To evaluate and characterize the New-World squirrel monkey as a primate model for experimental choroidal neovascularization (CNV) studies and to compare it with the current Old-World macaque monkey model. Methods Fibrovascular tissues (FVT) were elicited in 12 maculae of seven squirrel monkeys by laser photocoagulation using optimized laser parameters (532 nm, 0.05 second, 75 micro m, 650 mW). Follow-up fundus and fluorescein angiography (FA) examinations were conducted on postlaser days 30 and 35, followed by euthanasia and histologic analysis of tissues. For comparative evaluations, FVT development also was induced and analyzed in eight maculae of four macaque monkeys with laser parameters previously used in this species (514 nm, 0.1 second, 50 micro m, 390 and 455 mW). Results FVT developed in both primate species, consisting of fibrous tissue that contained vessels that ranged from sparse but identifiable capillaries to well-established neovascular networks. Overall, 65% of the photocoagulation sites in the squirrel monkey and 37% of sites in macaque monkey elicited development of FVT. Localized FVT ranged from modest to extensive thickenings of the choriocapillaris layer. Unexpectedly, 76% of the FVT sites in squirrel monkey eyes and 27% of the sites in macaque eyes showed diffuse FVT that expanded beyond the original photocoagulation sites, accompanied by neovascular infiltration of the retina. Conclusions Like the macaque, the squirrel monkey can be considered a useful primate model for experimental CNV investigations, while additionally offering certain species-specific advantages. Diffuse FVT permit studies of antiangiogenic therapies in areas distant from laser photocoagulative trauma sites.

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.