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1.
Polymers (Basel) ; 14(19)2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36236069

ABSTRACT

Shape-memory polymer (SMP) polyurethane foams have been applied as embolic devices and implanted in multiple animal models. These materials are oxidatively degradable and it is critical to quantify and characterize the degradation for biocompatibility assessments. An image-based method using high-resolution and magnification scans of histology sections was used to estimate the mass loss of the peripheral and neurovascular embolization devices (PED, NED). Detailed analysis of foam microarchitecture (i.e., struts and membranes) was used to estimate total relative mass loss over time. PED foams implanted in porcine arteries showed a degradation rate of ~0.11% per day as evaluated at 30-, 60-, and 90-day explant timepoints. NED foams implanted in rabbit carotid elastase aneurysms showed a markedly faster rate of degradation at ~1.01% per day, with a clear difference in overall degradation between 30- and 90-day explants. Overall, membranes degraded faster than the struts. NEDs use more hydrophobic foam with a smaller pore size (~150-400 µm) compared to PED foams (~800-1200 µm). Previous in vitro studies indicated differences in the degradation of the two polymer systems, but not to the magnitude seen in vivo. Implant location, animal species, and local tissue health are among the hypothesized reasons for different degradation rates.

2.
Cardiovasc Pathol ; 60: 107428, 2022.
Article in English | MEDLINE | ID: mdl-35430379

ABSTRACT

In this report, we showcase diffusible iodine-based contrast-enhanced computed tomography (DICE-CT) as a method for improving soft tissue visualization and reducing beam hardening artifact within a stented vessel. This technique is commonly used in our pathology lab to image soft tissue specimens with dense metal implants and to ensure reliable morphological analysis through clear delineation of tissue structures. For this report, a porcine right coronary artery with an implanted metal stent was scanned using both conventional and DICE-CT methods. Upon reconstruction, DICE-CT produced less beam hardening artifact in comparison to traditional micro-CT; furthermore, DICE-CT produced results with morphometric similarity to histology. Accordingly, these differences illustrated the clear advantage of using DICE-CT over conventional micro-CT when imaging soft tissue specimens with dense metal implants.


Subject(s)
Iodine , Stents , Animals , Coronary Vessels/diagnostic imaging , Metals , Swine , X-Ray Microtomography
3.
ACS Biomater Sci Eng ; 6(5): 2588-2599, 2020 05 11.
Article in English | MEDLINE | ID: mdl-32715083

ABSTRACT

The IMPEDE Embolization Plug is a catheter-delivered vascular occlusion device that utilizes a porous shape memory polymer foam as a scaffold for thrombus formation and distal coils to anchor the device within the vessel. In this study, we investigated the biological response of porcine arteries to the IMPEDE device by assessing the extent of healing and overall effectiveness in occluding the vessel at 30, 60, and 90 days. Compared to control devices (Amplatzer Vascular Plug and Nester Embolization Coils), the host response to IMPEDE showed increased cellular infiltration (accommodated by the foam scaffold), which led to advanced healing of the initial thrombus to mature collagenous connective tissue (confirmed by transmission electron microscopy (TEM)). Over time, the host response to the IMPEDE device included degradation of the foam by multinucleated giant cells, which promoted fibrin and polymer degradation and advanced the healing response. Device effectiveness, in terms of vessel occlusion, was evaluated histologically by assessing the degree of recanalization. Although instances of recanalization were often observed at all time points for both control and test articles, the mature connective tissue within the foam scaffold of the IMPEDE devices improved percent vessel occlusion; when recanalization was observed in IMPEDE-treated vessels, channels were exclusively peri-device rather than intradevice, as often observed in the controls, and the vessels mostly remained >75% occluded. Although total vessel occlusion provides the optimal ischemic effect, in cardiovascular pathology, there is a progressive ischemic effect on the downstream vasculature as a vessel narrows. As such, we expect a sustained ischemic therapeutic effect to be observed in vessels greater than 75% occluded. Overall, the current study suggests the IMPEDE device presents advantages over controls by promoting an enhanced degree of healing within the foam scaffold, which decreases the likelihood of intradevice recanalization and ultimately may lead to a sustained ischemic therapeutic effect.


Subject(s)
Embolization, Therapeutic , Smart Materials , Vascular Diseases , Animals , Blood Vessel Prosthesis , Polymers , Swine
4.
J Biomed Mater Res B Appl Biomater ; 108(5): 2238-2249, 2020 07.
Article in English | MEDLINE | ID: mdl-31961062

ABSTRACT

Recent studies utilizing shape memory polymer foams to coat embolizing coils have shown potential benefits over current aneurysm treatments. In the current study utilizing a rabbit-elastase aneurysm model, the performance of test article (foam-coated coil [FCC]) and control (bare platinum coils [BPCs]) devices were compared at 30, 90, and 180 days using micro-CT and histological assessments. The host response was measured by identifying the cells regionally present within the aneurysm, and assessing the degree of residual debris and connective tissue. The 3D reconstructions of aneurysms provided context for histologic findings, and aided in the overall aneurysm assessment. At all time points, >75% of the cells categorized in each aneurysm were associated with a bioactive yet biocompatible host response (vs. the remainder of cells that were associated with acute inflammation). The extracellular matrix exhibited a transition from residual fibrin at 30 days to a greater degree of connective tissue at 90 and 180 days. Although the control BPC-treated aneurysms exhibited a greater degree of connective tissue at the earliest time point examined (30 days), by 180 days, the FCC-treated aneurysms had more connective tissue and less debris overall than the control aneurysms. When considering cell types and extracellular matrix composition, the overall host response scores were significantly better in FCC-treated aneurysms at the later time point. Based on the results of these metrics, the FCC device may lead to an advanced tissue remodeling response over BPC occlusion devices.


Subject(s)
Coated Materials, Biocompatible/chemistry , Inflammation/physiopathology , Intracranial Aneurysm/therapy , Platinum/chemistry , Smart Materials/chemistry , Animals , Blood Vessel Prosthesis , Coated Materials, Biocompatible/metabolism , Fibrin/metabolism , Foreign-Body Reaction/pathology , Humans , Intracranial Aneurysm/surgery , Pancreatic Elastase/metabolism , Prosthesis Design , Rabbits , Risk Assessment , Smart Materials/metabolism , Time Factors , Treatment Outcome , X-Ray Microtomography
5.
J Mater Sci Mater Med ; 30(7): 79, 2019 Jun 25.
Article in English | MEDLINE | ID: mdl-31240399

ABSTRACT

Long-term, subcutaneously implanted continuous glucose biosensors have the potential to improve diabetes management and reduce associated complications. However, the innate foreign body reaction (FBR) both alters the local glucose concentrations in the surrounding tissues and compromises glucose diffusion to the biosensor due to the recruitment of high-metabolizing inflammatory cells and the formation of a dense, collagenous fibrous capsule. Minimizing the FBR has mainly focused on "passively antifouling" materials that reduce initial cellular attachment, including poly(ethylene glycol) (PEG). Instead, the membrane reported herein utilizes an "actively antifouling" or "self-cleaning" mechanism to inhibit cellular attachment through continuous, cyclic deswelling/reswelling in response to normal temperature fluctuations of the subcutaneous tissue. This thermoresponsive double network (DN) membrane is based on N-isopropylacrylamide (NIPAAm) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) (75:25 and 100:0 NIPAAm:AMPS in the 1st and 2nd networks, respectively; "DN-25%"). The extent of the FBR reaction of a subcutaneously implanted DN-25% cylindrical membrane was evaluated in rodents in parallel with a PEG-diacrylate (PEG-DA) hydrogel as an established benchmark biocompatible control. Notably, the DN-25% implants were more than 25× stronger and tougher than the PEG-DA implants while maintaining a modulus near that of subcutaneous tissue. From examining the FBR at 7, 30 and 90 days after implantation, the thermoresponsive DN-25% implants demonstrated a rapid healing response and a minimal fibrous capsule (~20-25 µm), similar to the PEG-DA implants. Thus, the dynamic self-cleaning mechanism of the DN-25% membranes represents a new approach to limit the FBR while achieving the durability necessary for long-term implantable glucose biosensors.


Subject(s)
Biosensing Techniques , Blood Glucose Self-Monitoring , Blood Glucose/analysis , Foreign-Body Reaction/prevention & control , Membranes, Artificial , Acrylamides/chemistry , Alkanesulfonates/chemistry , Animals , Biocompatible Materials , Collagen/chemistry , Hydrogels , Inflammation , Male , Materials Testing , Polyethylene Glycols/chemistry , Rats , Stress, Mechanical , Wound Healing
6.
Toxicol Pathol ; 47(3): 221-234, 2019 04.
Article in English | MEDLINE | ID: mdl-30844339

ABSTRACT

Pathologic evaluation is crucial to the study of medical devices and integral to the Food and Drug Administration and other regulatory entities' assessment of device safety and efficacy. While pathologic analysis is tailored to the type of device, it generally involves at a minimum gross and microscopic evaluation of the medical device and associated tissues. Due to the complex nature of some implanted devices and specific questions posed by sponsors, pathologic evaluation inherently presents many challenges in accurately assessing medical device safety and efficacy. This laboratory's experience in numerous collaborative projects involving veterinary pathologists, biomedical engineers, physicians, and other scientists has led to a set of interrelated assessments to determine pathologic end points as a means to address these challenges and achieve study outcomes. Thorough device evaluation is often accomplished by utilizing traditional paraffin histology, plastic embedding and microground sections, and advanced imaging modalities. Combining these advanced techniques provides an integrative, comprehensive approach to medical device pathology and enhances medical device safety and efficacy assessment.


Subject(s)
Device Approval/standards , Equipment Safety/standards , Equipment and Supplies/standards , Pathology/methods , Animals , Device Approval/legislation & jurisprudence , Equipment and Supplies/adverse effects , Histological Techniques/methods , Histological Techniques/standards , Humans , Models, Animal , United States , United States Food and Drug Administration
7.
Cardiovasc Pathol ; 36: 44-52, 2018.
Article in English | MEDLINE | ID: mdl-30014985

ABSTRACT

Cardiovascular implantable electronic devices (CIEDs) typically incorporate leads that directly contact the endocardium. Post-explant pathology evaluation of formalin-fixed CIED lead implant sites and downstream organs (i.e., lungs) can provide useful safety data to the US Food and Drug Administration; however, current regulatory guidelines do not mandate how the safety data are collected. In this paper, we outline a protocol for preclinical pathology evaluation of leads associated with CIEDs, which includes formalin fixation of the heart and lungs, gross evaluation, and qualitative and quantitative histologic evaluation. We recommend fixation of the whole heart with leads in situ alongside intratracheal formalin infusion; this enables rapid and effective preservation of target tissues and increases histologic quality to allow for accurate qualitative and quantitative pathology evaluation. Overall, we believe that our approach to pathology evaluation of leads may maximize information acquired from preclinical studies, leading to more accurate safety assessments. SUMMARY: This article introduces an established method for pathology evaluation and analysis of cardiac leads recommended for companies and researchers that seek approval from a regulatory body.


Subject(s)
Defibrillators, Implantable/adverse effects , Foreign-Body Reaction/pathology , Lung/pathology , Myocardium/pathology , Pacemaker, Artificial/adverse effects , Tissue Fixation/methods , Animals , Device Removal , Equipment Safety , Fixatives/pharmacology , Foreign-Body Reaction/diagnostic imaging , Formaldehyde/pharmacology , Lung/diagnostic imaging , Microtomy , Models, Animal , Paraffin Embedding , Perfusion , Prosthesis Design , Risk Assessment , X-Ray Microtomography
8.
ACS Biomater Sci Eng ; 4(12): 4104-4111, 2018.
Article in English | MEDLINE | ID: mdl-31633011

ABSTRACT

Towards achieveing a subcutaneously implanted glucose biosensor with long-term functionality, a thermoresponsive membrane previously shown to have potential to house a glucose sensing assay was evaluated herein for its ability to minimize the foriegn body reaction (FBR) and the resulting fibrous capsule. The severity of the FBR proportionally reduces diffusion of glucose to the sensor and hence sensor lifetime. However, efforts to reduce the FBR have largedly focused on anti-fouling materials that passively inhibit cellular attachment, particularly poly(ethylene glycol) (PEG). Herein, the extent of the FBR of a subcutaneously implanted "self-cleaning" cylindrical membrane was analyzed in rodents. This membrane represents an "actively anti-fouling" approach to reduce cellular adhesion. It is a thermoresponsive double network nanocomposite hydrogel (DNNC) comprised of poly(N-isopropylacrylamide) (PNIPAAm) and embedded polysiloxane nanoparticles. The membrane's cyclical deswelling/reswelling response to local body temperature fluctuations was anticipated to limit cellular accumulation. Indeed, after 30 days, the self-cleaning membrane exhibited a notably thin fibrous capsule (~30 µm) and increased microvascular density within 1 mm of the implant surface in comparison to a non-thermoresponsive, benchmark biocompatible control (PEG diacrylate, PEG-DA).

9.
J Biomed Mater Res B Appl Biomater ; 105(7): 1892-1905, 2017 10.
Article in English | MEDLINE | ID: mdl-27255687

ABSTRACT

The endovascular delivery of platinum alloy bare metal coils has been widely adapted to treat intracranial aneurysms. Despite the widespread clinical use of this technique, numerous suboptimal outcomes are possible. These may include chronic inflammation, low volume filling, coil compaction, and recanalization, all of which can lead to aneurysm recurrence, need for retreatment, and/or potential rupture. This study evaluates a treatment alternative in which polyurethane shape memory polymer (SMP) foam is used as an embolic aneurysm filler. The performance of this treatment method was compared to that of bare metal coils in a head-to-head in vivo study utilizing a porcine vein pouch aneurysm model. After 90 and 180 days post-treatment, gross and histological observations were used to assess aneurysm healing. At 90 days, the foam-treated aneurysms were at an advanced stage of healing compared to the coil-treated aneurysms and showed no signs of chronic inflammation. At 180 days, the foam-treated aneurysms exhibited an 89-93% reduction in cross-sectional area; whereas coiled aneurysms displayed an 18-34% area reduction. The superior healing in the foam-treated aneurysms at earlier stages suggests that SMP foam may be a viable alternative to current treatment methods. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1892-1905, 2017.


Subject(s)
Blood Vessel Prosthesis Implantation , Blood Vessel Prosthesis , Intracranial Aneurysm/surgery , Metals , Polyurethanes , Animals , Disease Models, Animal , Swine
10.
J Mech Behav Biomed Mater ; 63: 195-206, 2016 10.
Article in English | MEDLINE | ID: mdl-27419615

ABSTRACT

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.


Subject(s)
Aneurysm/therapy , Embolization, Therapeutic/instrumentation , Polymers/chemistry , Animals , Biocompatible Materials , Swine , Transition Temperature
11.
ASAIO J ; 62(3): 252-60, 2016.
Article in English | MEDLINE | ID: mdl-26735557

ABSTRACT

Thromboembolism is a common concern in ventricular assist device (VAD) therapy. Precise VAD response to pass-through thromboembolism needs to be studied in a controlled in vitro setting where specific pump parameters (i.e., power consumption, flow rates, impeller RPM) can be monitored while various types of thrombi are introduced. In this article, we describe a method for creating standardized fibrin thrombi that could be introduced into a mock circulatory loop for testing VAD response to thromboembolism. Donor equine blood collected using a sodium citrate was allowed to clot by adding calcium chloride (CaCl2) while a rotating component applied shear forces to the blood. This rotating force was applied at various speeds and at various distances into the blood. Resulting clots showed similar microscopic features to thrombi taken from explanted clinical VADs. Higher RPM of the rotating component and smaller clearances between the rotating component and the blood created clots that closely resembled ante-explant clots found within VADs in vivo. This method is an effective way to create artificial fibrin clots for use in in vitro experiments to test thromboembolism in VADs.


Subject(s)
Disease Models, Animal , Heart-Assist Devices/adverse effects , Thromboembolism , Animals , Horses , Thromboembolism/etiology
12.
J Ther Ultrasound ; 3: 17, 2015.
Article in English | MEDLINE | ID: mdl-26413296

ABSTRACT

BACKGROUND: Deep Bleeder Acoustic Coagulation (DBAC) is an ultrasound image-guided high-intensity focused ultrasound (HIFU) method proposed to automatically detect and localize (D&L) and treat deep, bleeding, combat wounds in the limbs of soldiers. A prototype DBAC system consisting of an applicator and control unit was developed for testing on animals. To enhance control, and thus safety, of the ultimate human DBAC autonomous product system, a thermal coagulation strategy that minimized cavitation, boiling, and non-linear behaviors was used. MATERIAL AND METHODS: The in vivo DBAC applicator design had four therapy tiles (Tx) and two 3D (volume) imaging probes (Ix) and was configured to be compatible with a porcine limb bleeder model developed in this research. The DBAC applicator was evaluated under quantitative test conditions (e.g., bleeder depths, flow rates, treatment time limits, and dose exposure time limits) in an in vivo study (final exam) comprising 12 bleeder treatments in three swine. To quantify blood flow rates, the "bleeder" targets were intact arterial branches, i.e., the superficial femoral artery (SFA) and a deep femoral artery (DFA). D&L identified, characterized, and targeted bleeders. The therapy sequence selected Tx arrays and determined the acoustic power and Tx beam steering, focus, and scan patterns. The user interface commands consisted of two buttons: "Start D&L" and "Start Therapy." Targeting accuracy was assessed by necropsy and histologic exams and efficacy (vessel coagulative occlusion) by angiography and histology. RESULTS: The D&L process (Part I article, J Ther Ultrasound, 2015 (this issue)) executed fully in all cases in under 5 min and targeting evaluation showed 11 of 12 thermal lesions centered on the correct vessel subsection, with minimal damage to adjacent structures. The automated therapy sequence also executed properly, with select manual steps. Because the dose exposure time limit (t dose ≤ 30 s) was associated with nonefficacious treatment, 60-s dosing and dual-dosing was also pursued. Thrombogenic evidence (blood clotting) and collagen denaturation (vessel shrinkage) were found in necropsy and histologically in all targeted SFAs. Acute SFA reductions in blood flow (20-30 %) were achieved in one subject, and one partial and one complete vessel occlusion were confirmed angiographically. The complete occlusion case was achieved with a dual dose (90 s total exposure) with focal intensity ≈500 W/cm(2) (spatial average, temporal average). CONCLUSIONS: While not meeting all in vivo objectives, the overall performance of the DBAC applicator was positive. In particular, D&L automation workflow was verified during each of the tests, with processing times well under specified (10 min) limits, and all bleeder branches were detected and localized. Further, gross necropsy and tissue examination confirmed that the HIFU thermal lesions were coincident with the target vessel locations in over 90 % of the multi-array dosing treatments. The SFA/DFA bleeder models selected, and the protocols used, were the most suitable practical model options for the given DBAC anatomical and bleeder requirements. The animal models were imperfect in some challenging aspects, including requiring tissue-mimicking material (TMM) standoffs to achieve deep target depths, thereby introducing device-tissue motion, with resultant imaging artifacts. The model "bleeders" involved intact vessels, which are subject to less efficient heating and coagulation cascade behaviors than true puncture injuries.

13.
Tex Heart Inst J ; 41(4): 389-94, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25120391

ABSTRACT

Mechanical cardiac unloading with use of a left ventricular assist device (LVAD) is associated with substantial improvements in left ventricular function and enables subsequent LVAD explantation in some patients. We describe the case of a 35-year-old man with dilated nonischemic cardiomyopathy who was supported with an LVAD for 9 months. After the device was removed, he led a normal life for 13 years and 4 months. However, at 49 years of age, he presented with new signs and symptoms of heart failure, necessitating implantation of a 2nd LVAD. Afterwards, he has remained asymptomatic. This case is unique in that the patient lived a normal life for longer than a decade before renewed left ventricular decompensation necessitated repeat LVAD therapy. Histologic examination revealed few changes between the first device's removal in 1999 and the 2nd device's implantation in 2012.


Subject(s)
Cardiomyopathy, Dilated/therapy , Device Removal , Heart-Assist Devices , Ventricular Function, Left , Adult , Biopsy , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/physiopathology , Humans , Male , Prosthesis Design , Recovery of Function , Recurrence , Retreatment , Time Factors , Treatment Outcome
14.
J Biomed Mater Res A ; 102(5): 1231-42, 2014 May.
Article in English | MEDLINE | ID: mdl-23650278

ABSTRACT

Cerebral aneurysms treated by traditional endovascular methods using platinum coils have a tendency to be unstable, either due to chronic inflammation, compaction of coils, or growth of the aneurysm. We propose to use alternate filling methods for the treatment of intracranial aneurysms using polyurethane-based shape memory polymer (SMP) foams. SMP polyurethane foams were surgically implanted in a porcine aneurysm model to determine biocompatibility, localized thrombogenicity, and their ability to serve as a stable filler material within an aneurysm. The degree of healing was evaluated via gross observation, histopathology, and low vacuum scanning electron microscopy imaging after 0, 30, and 90 days. Clotting was initiated within the SMP foam at time 0 (<1 h exposure to blood before euthanization), partial healing was observed at 30 days, and almost complete healing had occurred at 90 days in vivo, with minimal inflammatory response.


Subject(s)
Aneurysm/pathology , Aneurysm/therapy , Implants, Experimental , Materials Testing , Polyurethanes/pharmacology , Animals , Blood Vessels/drug effects , Blood Vessels/pathology , Blood Vessels/ultrastructure , Cell Proliferation/drug effects , Disease Models, Animal , Embolization, Therapeutic , Inflammation/pathology , Neointima/pathology , Neovascularization, Physiologic/drug effects , Staining and Labeling , Sus scrofa , Sutures , Wound Healing/drug effects
15.
ASAIO J ; 59(5): 486-92, 2013.
Article in English | MEDLINE | ID: mdl-23851452

ABSTRACT

A left atrial pressure (LAP) monitoring system was developed for guiding the management of patients with heart failure. The LAP sensor is implanted into the left atrium via transseptal catheterization and affixed to the interatrial septum by nitinol anchors. The long-term safety of permanent implantation of the LAP sensor in patients was evaluated based on the comparative pathology in animals. Tissue specimens of the LAP sensor from 7 patients, 49 canines, and 14 ovine were examined for thrombosis and tissue overgrowth. Implant duration ranged from 22 to 1,686 days. Gross examination showed minimal-to-moderate tissue overgrowth with no evidence of migration, erosion, or perforation. There was no excessive host-to-device reaction or active thrombogenesis in any of the subjects that followed the antithrombotic therapy protocol. Micro-computed tomography scanning confirmed the structural integrity of the device. Low vacuum scanning electron microscopy and histology showed neoendocardial tissue overgrowth with no inflammation or fibrin. The pathology of both animal models was found to closely approximate the pathology in humans and favorably supports the long-term safety of the device.


Subject(s)
Atrial Pressure , Heart Atria/pathology , Heart Failure/diagnosis , Heart Failure/physiopathology , Transducers, Pressure , Animals , Artifacts , Dogs , Equipment Failure , Heart Failure/therapy , Humans , Microscopy, Electron, Scanning , Models, Animal , Patient Safety , Pressure , Sheep , Thrombosis/physiopathology , Time Factors , X-Ray Microtomography
16.
Cardiovasc Pathol ; 22(5): 408-15, 2013.
Article in English | MEDLINE | ID: mdl-23523187

ABSTRACT

UNLABELLED: Heart failure is a leading cause of death in human populations, and as people live longer, it is becoming an increasingly prominent problem. Because of the insufficient numbers of donor hearts, physicians and engineers are turning to mechanical circulatory support in the form of ventricular assist devices (VADs). Their clinical performance and increasing availability of various types, sizes, and functions are increasing VAD recognition. However, for any implantable medical device, especially one that is life supporting, performance and safety must be evaluated both pre- and postmarket. It has been demonstrated that specific pathology analysis can provide unique and important information to augment the evaluation of performance and safety. To help ensure the safety and efficacy of a device, we propose that regulatory agencies include pathology analysis by experienced, independent pathologists with relevant expertise as an integral component of device submissions. We believe that this analysis should include both gross and microscopic components and, when warranted, supplementary data obtained through radiography, electron microscopy, or both. The pathology data acquired through these analyses should be correlated with clinical data to yield a more thorough data set for submission to the governing regulatory body. Submitting this coordinated analysis of data will demonstrate to regulatory agencies (United States Food and Drug Administration, Therapeutic Goods Administration, Brazilian Health Surveillance Agency, etc.) that the device manufacturer shares their objective: making medical devices as safe and effective as possible. SUMMARY: This review of ventricular assist devices introduces a recommended protocol for pathology evaluations of devices from organizations or researchers seeking approval by a governing regulatory agency.


Subject(s)
Heart-Assist Devices , Animals , Clinical Trials as Topic , Equipment Safety/standards , Heart Failure/pathology , Heart Failure/surgery , Heart Transplantation , Heart-Assist Devices/classification , Heart-Assist Devices/standards , Humans , Prosthesis Design , United States , United States Food and Drug Administration
17.
Comp Med ; 62(4): 251-6, 2012 Aug.
Article in English | MEDLINE | ID: mdl-23043776

ABSTRACT

Captive-raised red drum fish were observed with phenotypic abnormalities, including deformities of the spine, jaw, and cephalic region, that were consistent with vitamin C deficiency during the larval stage. In light of their visible exterior skeletal abnormalities, we suspected that the affected fish would also have abnormal otoliths. Otoliths are dense calcareous structures that function in fish hearing. We hypothesized that abnormal fish would have irregular otoliths that would alter behavior and cortisol levels as compared with those of phenotypically normal fish. The normal and abnormal fish had statistically significant differences in behavior, cortisol levels, and otolith volume and density. MicroCT assessment of abnormal fish revealed operculum abnormalities, malocclusions, and several types of otolith malformations. Therefore, the affected fish had not only an abnormal skeletal appearance but also significantly abnormal behavior and cortisol responses.


Subject(s)
Ascorbic Acid Deficiency/veterinary , Behavior, Animal/physiology , Fish Diseases/pathology , Hydrocortisone/blood , Otolithic Membrane/pathology , Perciformes , Animals , Ascorbic Acid Deficiency/pathology , Jaw/pathology , Radioimmunoassay/veterinary , X-Ray Microtomography/veterinary
18.
Ann Biomed Eng ; 40(4): 883-97, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22101759

ABSTRACT

Shape memory polymer (SMP) foam possesses structural and mechanical characteristics that make them very promising as an alternative treatment for intracranial aneurysms. Our SMP foams have low densities, with porosities as high as 98.8%; favorable for catheter delivery and aneurysm filling, but unfavorable for attenuating X-rays. This lack of contrast impedes the progression of this material becoming a viable medical device. This paper reports on increasing radio-opacity by incorporating a high-Z element, tungsten particulate filler to attenuate X-rays, while conserving similar physical properties of the original non-opacified SMP foams. The minimal amount of tungsten for visibility was determined and subsequently incorporated into SMP foams, which were then fabricated into samples of increasing thicknesses. These samples were imaged through a pig's skull to demonstrate radio-opacity in situ. Quantification of the increase in image contrast was performed via image processing methods and standard curves were made for varying concentrations of tungsten doped solid and foam SMP. 4% by volume loading of tungsten incorporated into our SMP foams has proven to be an effective method for improving radio-opacity of this material while maintaining the mechanical, physical and chemical properties of the original formulation.


Subject(s)
Biocompatible Materials/chemistry , Intracranial Aneurysm/therapy , Materials Testing , Polymers/chemistry , Biocompatible Materials/therapeutic use , Humans , Polymers/therapeutic use , X-Rays
19.
J Am Anim Hosp Assoc ; 47(6): e138-44, 2011.
Article in English | MEDLINE | ID: mdl-22058361

ABSTRACT

A 4 yr old male castrated Labrador retriever was evaluated for a short history of inappetance, lethargy, small-bowel diarrhea, polyuria, and polydipsia. Clinicopathologic abnormalities were consistent with protein-losing nephropathy and renal azotemia. Expansive infectious disease testing implicated Babesia gibsoni via whole blood polymerase chain reaction. Renal histopathology results were consistent with membranoproliferative glomerulonephritis and immune complex deposition. The dog was treated with azithromycin, atovaquone, and one dose of corticosteroids/cyclophosphamide. Three months after therapy was completed, the dog was clinically healthy, and all clinicopathologic abnormalities (including Babesia species polymerase chain reaction) had resolved. Atypical presentations of Babesia gibsoni should be considered with proteinuric nephropathy.


Subject(s)
Babesiosis/veterinary , Dog Diseases/drug therapy , Kidney Diseases/veterinary , Animals , Antiprotozoal Agents/administration & dosage , Atovaquone/administration & dosage , Azithromycin/administration & dosage , Babesia/genetics , Babesia/isolation & purification , Babesiosis/complications , Babesiosis/drug therapy , Cyclophosphamide/administration & dosage , DNA, Bacterial/analysis , Dog Diseases/pathology , Dogs , Kidney Diseases/complications , Kidney Diseases/drug therapy , Male , Polymerase Chain Reaction/veterinary , Proteinuria/veterinary
20.
Top Companion Anim Med ; 26(3): 143-53, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21782145

ABSTRACT

Presence of suspected primary glomerular disease is the most common and compelling reason to consider renal biopsy. Pathologic findings in samples from animals with nephritic or nephrotic glomerulopathies, as well as from animals with persistent subclinical glomerular proteinuria that is not associated with advanced chronic kidney disease, frequently guide treatment decisions and inform prognosis when suitable specimens are obtained and examined appropriately. Ultrasound-guided needle biopsy techniques generally are satisfactory; however, other methods of locating or approaching the kidney, such as manual palpation (e.g., in cats), laparoscopy, or open surgery, also can be used. Visual assessment of the tissue content of needle biopsy samples to verify that they are renal cortex (i.e., contain glomeruli) as they are obtained is a key step that minimizes the submission of uninformative samples for examination. Adequate planning for a renal biopsy also requires prior procurement of the fixatives and preservatives needed to process and submit samples that will be suitable for electron microscopic examination and immunostaining, as well as for light microscopic evaluation. Finally, to be optimally informative, renal biopsy specimens must be processed by laboratories that routinely perform the required specialized examinations and then be evaluated by experienced veterinary nephropathologists. The pathologic findings must be carefully integrated with one another and with information derived from the clinical investigation of the patient's illness to formulate the correct diagnosis and most informative guidance for therapeutic management of the animal's glomerular disease.


Subject(s)
Biopsy, Needle/veterinary , Cat Diseases/pathology , Dog Diseases/pathology , Glomerulonephritis/veterinary , Animals , Biopsy, Needle/methods , Cat Diseases/diagnosis , Cats , Dog Diseases/diagnosis , Dogs , Glomerulonephritis/diagnosis , Glomerulonephritis/pathology
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