Towards Non-thrombogenic Performance of Blood Recirculating Devices

Implantable blood recirculating devices have provided life saving solutions to patients with severe cardiovascular diseases. However, common problems of hemolysis and thromboembolism remain an impediment to these devices. In this article, we present a brief review of the work by several groups in the field that has led to the development of new methodologies that may facilitate achieving the daunting goal of optimizing the thrombogenic performance of blood recirculating devices. The aim is to describe work which pertains to the interaction between flow-induced stresses and the blood constituents, and that supports the hypothesis that thromboembolism in prosthetic blood recirculating devices is initiated and maintained primarily by the non-physiological flow patterns and stresses that activate and enhance the aggregation of blood platelets, increasing the risk of thromboembolism and cardioembolic stroke. Such work includes state-of-the-art numerical and experimental tools used to elucidate flow-induced mechanisms leading to thromboembolism in prosthetic devices. Following the review, the paper describes several efforts conducted by some of the groups active in the field, and points to several directions that should be pursued in the future in order to achieve the goal for blood recirculating prosthetic devices becoming more effective as destination therapy in the future.     

Designing for Scale: Development of the ReMotion Knee for Global Emerging Markets

Amputees living in developing countries have a profound need for affordable and reliable lower limb prosthetic devices. The World Health Organization estimates there are approximately 30 million amputees living in low-income countries, with up to 95% lacking access to prosthetic devices. Effective prosthetics can significantly affect the lives of these amputees by increasing opportunity for employment and providing improvements to long-term health and well-being. However, current solutions are inadequate: state-of-the-art solutions from the US and Europe are cost-prohibitive, while low-cost devices have been challenged by poor quality and/or unreliable performance, and have yet to achieve large scale impact. The introduction of new devices is hampered by the lack of a cohesive prosthetics industry in low-income areas; the current network of low-cost prosthetic clinics is informal and loosely organized with significant disparities in geography, patient volume and demographics, device procurement, clinical and logistical infrastructure, and funding. At D-Rev (Design Revolution) we are creating the ReMotion Knee, which is an affordable polycentric prosthetic knee joint that performs on par with devices in more industrialized regions, like the US and Europe. As of September 2012, over 4200 amputees have been fitted with the initial version of the ReMotion Knee through a partnership with the JaipurFoot Organization, with an 79% compliance rate after 2 years. We are currently scaling production of the ReMotion Knee using centralized manufacturing and distribution to serve the existing clinics in low-income countries and increase the availability of devices for amputees without access to appropriate care. At D-Rev, we develop products that target these customers through economically-sustainable models and provide a measurable impact in the lives of the world’s amputees.     

Application of robotics to prosthetic control

Multiaxis robotic and prosthetic systems have a number of common characteristics such that control techniques for robots may sometimes be adapted for prosthetic devices. One characteristic that is particularly important for these systems is that good performance over a wide range of motion and loads is difficult since it is dependent upon complex time-varying, nonlinear dynamics. This paper gives an example of the complexity of the dynamics for a two degree-of-freedom, double-inverted pendulum which has been used as a model for study of biped locomotion. Two different methods called the “inverse plant” and State Space Memory, now being considered for robotic mechanisms, are then presented which base the control on the dynamics of the system and may have application for prosthetic devices.     

Problems in Design of Neuro-controlled Prosthetic Devices

One of the most promising ways of constructing modern prosthetic control systems would be to use electrical control signals recorded from peripheral neural tissue. In this work the construction of such systems is analyzed in order to upgrade modern technical devices and methods that are used to design these systems. The requirements for technical devices and methods used to record and process neural signals and rules are also considered. The efficiency of the systems and methods is estimated and described. A generalized structure of neural prosthetic control systems and a way of preprocessing control signals to provide more efficient information transfer are suggested.     

Preoperative candidate evaluations for retinal prosthesis trials

With the development of retinal prostheses, the first clinical trials for these devices are being planned or are already underway. Yet the candidate selection criteria and the preparation of early recipients have received very little attention. As clinical trials grow in scope, the need for such issues will become increasingly important. Especially in preliminary stages of clinical trials, it is absolutely vital to develop the preoperative evaluations of candidates in identifying the suitable candidate for retinal prosthesis implants. This paper addresses the preoperative evaluations of candidates that may provide insight into selecting potential candidates for retinal prosthetic devices. Screening an ideal candidate is complex and, at the minimum, should include medical evaluations, visual function tests, assessments of psychological status, motivation, expectations, as well as rehabilitation capabilities. This will ensure that appropriate candidates are selected, candidate expectations are managed, and success with the retinal prosthetic devices is maximized.     

Drug/device combinations for local drug therapies and infection prophylaxis

Combination devices-those comprising drug releasing components together with functional prosthetic implants-represent a versatile, emerging clinical technology promising to provide functional improvements to implant devices in several classes. Landmark antimicrobial catheters and the drug-eluting stent have heralded the entrance, and significantly, routes to FDA approval, for these devices into clinical practice. This review describes recent strategies creating implantable combination devices. Most prominent are new combination devices representing current orthopedic and cardiovascular implants with new added capabilities from on-board or directly associated drug delivery systems are now under development. Wound coverings and implantable sensors will also benefit from this combination enhancement. Infection mitigation, a common problem with implantable devices, is a current primary focus. On-going progress in cell-based therapeutics, progenitor cell exploitation, growth factor delivery and advanced formulation strategies will provide a more general and versatile basis for advanced combination device strategies. These seek to improve tissue-device integration and functional tissue regeneration. Future combination devices might best be completely re-designed de novo to deliver multiple bioactive agents over several spatial and temporal scales to enhance prosthetic device function, instead of the current 'add-on' approach to existing implant device designs never originally intending to function in tandem with drug delivery systems.     

Synthetic grafts for anterior cruciate ligament rupture: 19-year outcome study

Artificial ligaments for ACL replacement have been widely used in the 1980s and early 1990s in orthopaedic surgery. Synthetic devices have been utilized either as a prosthetic material or as an augmentation for a biological ACL graft substitute. The initial enthusiasm surrounding the introduction of synthetic graft materials stemmed from their lack of donor morbidity, their abundant supply and significant strength of these devices. The disadvantages in long-term follow-up were found to be cross-infections, immunological responses, tunnels osteolysis, femural and tibial fractures, foreign-body synovitis and knee osteoarthritis.A total of 126 patients were treated with artificial ACL substitution with polyethylene terephthalate (PET) synthetic ligaments in our Institute between 1986 and 1990. Of the original group, 51 sportsmen aged 15 to 40 were followed-up at a mean of 19 years (range 17.5 to 20.6 years) after surgery. Assessment was made with KOOS and IKDC score, Tegner activity scale, clinical examination, KT-1000 arthrometer, and X-ray evaluation.Of the 51 patients followed-up, 27.5% were found to have ruptured their PET ligaments and 100% presented degenerative osteoarthritis at the X-ray evaluation according to Ahlbäck radiological classification of arthritis. The objective evaluation showed functional impairment in 29.4% with an average reduction of 3 points in the Tegner activity scale.The osteoarthritis observed in all patients prompted us to avoid the diffusion of this surgical technique. Although in theory well-conceived, studies have yet to substantiate the function of these augmentation devices or to show clinical better results than those achieved with isolated autograft or allograft ACL substitutes.     

An alginate hydrogel dura mater replacement for use with intracortical electrodes

The collagenous dura mater requires a secure closure following implantation of neural prosthetic devices to avoid complications due to cerebrospinal fluid leakage and infections. Alginate was previously suggested for use as a dural sealant. The liquid application and controllable gelling conditions enable alginate to conform to the unique geometries of a neural prosthetic device and the surrounding dura mater to create a barrier with the external environment. In this study, we evaluated the use of alginate as a method to securely reclose a dural defect and seal around an untethered microscale neural probe in the rabbit model. After 3 days and 3 weeks, the sealing strength of alginate remained eight times greater than normal rabbit intracranial pressure and similar in both the presence and absence of a penetrating neural probe. For time points up to 3 months, there was no significant difference in dura mater fibrosis or thickness between alginate and controls. Application of alginate to a dural defect results in a watertight seal that remains intact while the dura mater reforms. These findings indicate that alginate is an effective tool for sealing around microscale neural probes and suggests broader application as a sealant for larger neural prosthetic devices.     

Towards a Neurotransmitter-Based Retinal Prosthesis Using an Inkjet Print-head

Electronic chips that provide a patterned stimulus to cells in the retina may provide a viable treatment for age-related macular degeneration. A surrogate MEMS device, in the form of a print-head from a desktop printer, has been used to eject a pattern of neurotransmitters (bradykinin) onto living rat pheochromocytoma (PC12) cells. Fluorescent calcium imaging was used to measure the patterned stimulation of individual cells. The chemical stimulation of cells by directed microfluidic delivery may have applications in retinal prosthetic devices, and in other prosthetic implants in the nervous system.     

General-purpose filter design for neural prosthetic devices

Brain-driven interfaces depend on estimation procedures to convert neural signals to inputs for prosthetic devices that can assist individuals with severe motor deficits. Previous estimation procedures were developed on an application-specific basis. Here we report a coherent estimation framework that unifies these procedures and motivates new applications of prosthetic devices driven by action potentials, local field potentials (LFPs), electrocorticography (ECoG), electroencephalography (EEG), electromyography (EMG), or optical methods. The brain-driven interface is described as a probabilistic relationship between neural activity and components of a prosthetic device that may take on discrete or continuous values. A new estimation procedure is developed for action potentials, and a corresponding procedure is described for field potentials and optical measurements. We test our framework against dominant approaches in an arm reaching task using simulated traces of ensemble spiking activity from primary motor cortex (MI) and a wheelchair navigation task using simulated traces of EEG-band power. Adaptive filtering is incorporated to demonstrate performance under neuron death and discovery. Finally, we characterize performance under model misspecification using physiologically realistic history dependence in MI spiking. These simulated results predict that the unified framework outperforms previous approaches under various conditions, in the control of position and velocity, based on trajectory and endpoint mean squared errors.     

A novel vacuum assisted closure therapy model for use with percutaneous devices

Long-term maintenance of a dermal barrier around a percutaneous prosthetic device remains a common clinical problem. A technique known as Negative Pressure Wound Therapy (NPWT) uses negative pressure to facilitate healing of impaired and complex soft tissue wounds. However, the combination of using negative pressure with percutaneous prosthetic devices has not been investigated. The goal of this study was to develop a methodology to apply negative pressure to the tissues surrounding a percutaneous device in an animal model; no tissue healing outcomes are presented. Specifically, four hairless rats received percutaneous porous coated titanium devices implanted on the dorsum and were bandaged with a semi occlusive film dressing. Two of these animals received NPWT; two animals received no NPWT and served as baseline controls. Over a 28-day period, both the number of dressing changes required between the two groups as well as the pressures were monitored. Negative pressures were successfully applied to the periprosthetic tissues in a clinically relevant range with a manageable number of dressing changes. This study provides a method for establishing, maintaining, and quantifying controlled negative pressures to the tissues surrounding percutaneous devices using a small animal model.     

Venous Thrombosis on Prosthetic Surfaces: Evolution and Blood Coagulation Studies in a Nonhuman Primate Model

Thrombi deposited on prosthetic devices in the superior vena cava of the rhesus monkey were studied by morphologic and biochemical technics. Glass or silicone-coated glass (SCG) rings were implanted for 30 minutes to 14 days. Thrombus was deposited on the surface of each prosthetic device, and deposition was much greater and more rapid on glass surfaces than on SCG surfaces. On SCG surfaces, initial deposits consisting of single platelets, small platelet aggregates and erythrocytes were seen by scanning electron microscopy. These were followed by larger platelet aggregates, fibrin and, much later, leukocytes. Transmission electron micrographs revealed disintegration of the platelets forming aggregates and an osmiophilic deposit on the prosthetic surface. Shortened partial thromboplastin times were observed in all test animals but the sham-operated one, and therefore may be predictive of thrombus formation.     

Pathogenic organisms in hip joint infections

Infections of the hip joint are usually of bacterial etiology. Only rarely, an infectious arthritis is caused in this localization by viruses or fungi. Native joint infections of the hip are less common than infections after implantation of prosthetic devices. Difficulties in prosthetic joint infections are, (I) a higher age of patients, and, thus an associated presence of other medical risk factors, (II) often long courses of treatment regimes depending on the bacterium and its antibiotic resistance, (III) an increased mortality, and (IV) a high economic burden for removal and reimplantation of an infected prosthetic device. The pathogenic mechanisms responsible for articular infections are well studied only for some bacteria, e.g. Staphylococcus aureus, while others are only partially understood. Important known bacterial properties and microbiological characteristics of infection are the bacterial adhesion on the native joint or prosthetic material, the bacterial biofilm formation, the development of small colony variants (SCV) as sessile bacterial types and the increasing resistance to antibiotics.     

Theory and design of capacitor electrodes for chronic stimulation

Conventional metal electrodes generate electrochemical byproducts during stimulation of nerve or muscle. These byproducts may cause tissue damage, especially with the long-term stimulation necessary with neural prosthetic devices. To prevent the possibility of such damage, completely insulated electrodes have been devised which deliver current pulses by capacitive charging of the electrode surface, not involving electrochemical reactions. Anodised discs of porous tantalum, 1·0 mm in diameter and 0·25 mm thick, can deliver 0·5 ms, 5 mA pulses. Such electrodes are available as components of commercial capacitors and are easily adapted for biological use. The design may be optimised by mathematical analysis of an equivalent electrical circuit.In vitro tests demonstrate a clear advantage of these electrodes over capacitively coupled platinum-iridium electrodes in preventing oxidation-reduction reactions. The electrodes are stable on chronic implantation and should provide a safer interface between neural prosthetic devices and human tissue.     

Design considerations for the brain-machine interface

Implantation of prosthetic devices designed to complement the function of the human brain is a rare but well recognized innovative treatment for some patients. If this technique is to become clinically useful special attention will have to be paid to the bio-engineering requirements of the prosthesis-brain interface.     

Q fever endocarditis associated with a cardiovascular implantable electronic device

Cardiovascular implantable electronic devices (CIEDs) are frequently related to endocarditis. Most cases of intravascular CIED infections are usually related to skin flora, but a few cases may occur with negative blood culture. Coxiella burnetii is one of the main causes of blood culture-negative endocarditis in native and prosthetic valves, but to date no cases related to CIED have been published. Herein we report two cases of Q fever endocarditis related to these non-valvular cardiovascular devices.     

Effects of Glial Cells on Electrode Impedance Recorded from Neural Prosthetic Devices <Emphasis Type="Italic">In Vitro</Emphasis>

Neural prosthetic devices hold the potential to be used in the treatment of a variety of neurological disorders. However, their long-term clinical success is currently limited by the ability to achieve stable interfaces between devices and the CNS. Immunohistochemical analysis has shown that cellular responses occur in tissue surrounding implanted devices. These cellular responses have been correlated with the impedance measured from device electrodes, leading to the hypothesis that a possible mechanism resulting in inconsistent device performance is the formation of an electrically insulating glial sheath at the implantation site. However, little is known about what cellular and tissue changes affect impedance values and thus contribute to the decreases in electrode performance. We have designed an in vitro system in which cell conditions can be varied within an artificial tissue matrix surrounding a neural prosthetic device. In this study, high-density cultures of glial cells were analyzed by immunohistochemical methods and impedance spectroscopy. Astrocytes and microglia were cultured at various ratios within the matrix surrounding the probes, and were observed over a period of 2 weeks. Cell seeding conditions and confocal images were compared to impedance data to enable the effects of glial cell type on electrode impedance to be determined.     

Control of multifunctional prosthetic hands by processing the electromyographic signal

The human hand is a complex system, with a large number of degrees of freedom (DoFs), sensors embedded in its structure, actuators and tendons, and a complex hierarchical control. Despite this complexity, the efforts required to the user to carry out the different movements is quite small (albeit after an appropriate and lengthy training). On the contray, prosthetic hands are just a pale replication of the natural hand, with significantly reduced grasping capabilities and no sensory information delivered back to the user. Several attempts have been carried out to develop multifunctional prosthetic devices controlled by electromyographic (EMG) signals (myoelectric hands), harness (kinematic hands), dimensional changes in residual muscles, and so forth, but none ofthese methods permits the "natural" control of more than two DoFs. This article presents a review of the traditional methods used to control artificial hands by means of EMG signal, in both the clinical and research contexts, and introduces what could be the future developments in the control strategy of these devices.     

The intercellular adhesin locus ica is present in clinical isolates of Staphylococcus aureus from bacteremic patients with infected and uninfected prosthetic joints

Although polysaccharide intercellular adhesin (PIA) is thought to be crucial in the pathogenesis of prosthetic device infections caused by Staphylococcus epidermidis, its role in prosthetic device infections caused by Staphylococcus aureus is unknown. To assess the clinical impact of PIA production, isolates from 15 prospectively identified cases of S. aureus bacteremia in patients with prosthetic joints (8 infected, 7 uninfected) were characterized for biofilm production, hemagglutination, and the presence of a 419-bp amplification product within icaA. Although icaA was present in all 15 isolates, none of the isolates produced hemagglutination and only one isolate (from a patient with an uninfected prosthetic device) weakly produced biofilm in vitro. These results support the observation that the ica locus is conserved between S. epidermidis and S. aureus and that PIA may be expressed only under in vivo conditions. Future investigations should include animal models to approximate the complex milieu surrounding implanted prosthetic medical devices. Received: 19 June 2000     

Tissue-derived biomaterials and their use in cardiovascular prosthetic devices

A variety of tissues and tissue components, ranging from allograft and xenograft tissues to albumin- and collagen-coated synthetic materials, have been used to fabricate cardiovascular prosthetic devices. Tissue-derived biomaterials include both viable and non-viable tissues as well as individual tissue components which have undergone some degree of preimplantation processing. A review of the biochemistry, immunogenicity, mechanical properties, physicochemical properties, preimplantation processing and the morphology of the following cardiovascular prostheses are discussed: heart valve bioprostheses and allografts; blood vessel allografts; biologic vascular grafts; and, protein-coated vascular prostheses. This review focuses on the generic aspects of prosthetic device fabrication using tissue-derived biomaterials, realizing that specific differences between various commercially available prostheses may exist.