Noninvasive thrombectomy of graft by nano-magnetic ablating particles.

Artificial vascular treatment is an emerging interdisciplinary subject of medicine. Although the use of artificial vessels has led to many successful advancements, blood clotting remains a major challenge, especially in terms of mural clots created along the vessel wall that do not completely block the vessel. The main objective of this study is to present a method for declotting artificial vessels. This research introduces a novel thrombectomy technique in artificial vessels by employing nano-magnetic particles under a rotating magnetic field to remove mural clots in artificial vessels. A mathematical model describes the relationship between process parameters. In vitro tests confirm the feasibility of nano-magnetic thrombectomy in cleaning and declotting artificial vessels. The results show that the clot fragments are nano-sized, which eliminates the risk of distal emboli as a concern of using current atherectomy techniques. Meanwhile, no damage to the artificial vessels is observed. The results show that the frequency of rotating the magnetic field has the greatest effect on clot removal. The conceptual principles stated in this study also have the potential to be used in other vascular depositions, such as the accumulation of lipids, and calcification atherosclerosis.

3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels.

Cellular models are needed to study human development and disease in vitro, and to screen drugs for toxicity and efficacy. Current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Here, we develop a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization. As an example application, we bioprint induced pluripotent stem cell-derived cardiac microtissue models with spatially controlled cardiomyocyte and fibroblast cell ratios to replicate the structural and functional features of scarred cardiac tissue that arise following myocardial infarction, including reduced contractility and irregular electrical activity. The bioprinted in vitro model is combined with functional readouts to probe how various pro-regenerative microRNA treatment regimes influence tissue regeneration and recovery of function as a result of cardiomyocyte proliferation. This method is useful for a range of biomedical applications, including the development of precision models to mimic diseases and the screening of drugs, particularly where high cell densities and heterogeneity are important.

Preliminary Evaluation of 3D Printed Chitosan/Pectin Constructs for Biomedical Applications.

In the present study, chitosan (CS) and pectin (PEC) were utilized for the preparation of 3D printable inks through pneumatic extrusion for biomedical applications. CS is a polysaccharide with beneficial properties; however, its printing behavior is not satisfying, rendering the addition of a thickening agent necessary, i.e., PEC. The influence of PEC in the prepared inks was assessed through rheological measurements, altering the viscosity of the inks to be suitable for 3D printing. 3D printing conditions were optimized and the effect of different drying procedures, along with the presence or absence of a gelating agent on the CS-PEC printed scaffolds were assessed. The mean pore size along with the average filament diameter were measured through SEM micrographs. Interactions among the characteristic groups of the two polymers were evident through FTIR spectra. Swelling and hydrolysis measurements confirmed the influence of gelation and drying procedure on the subsequent behavior of the scaffolds. Ascribed to the beneficial pore size and swelling behavior, fibroblasts were able to survive upon exposure to the ungelated scaffolds.

Biological evaluation of preceramic organosilicon polymers for various healthcare and biomedical engineering applications: A review.

Preceramic organosilicon materials combining the properties of a polymer and an inorganic ceramic phase are of great interest to scientists working in biomedical sciences. The interdisciplinary nature of organosilicon polymers and their molecular structures, as well as their diversity of applications have resulted in an unprecedented range of devices and synergies cutting across unrelated fields in medicine and engineering. Organosilicon materials, especially the polysiloxanes, have a long history of industrial and medical uses in many versatile aspects as they can be easily fabricated into complex-shaped products using a wide variety of computer-aided or polymer manufacturing techniques. Thus far, intensive research activities have been mainly devoted to the processing of preceramic organosilicon polymers toward magnetic, electronic, structural, optical, and not biological applications. Herein we present innovative research studies and recent developments of preceramic organosilicon polymers at the interface with biological systems, displaying the versatility and multi-functionality of these materials. This article reviews recent research on preceramic organosilicon polymers and corresponding composites for bone tissue regeneration and medical engineering implants, focusing on three particular topics: (a) surface modifications to create tailorable and bioactive surfaces with high corrosion resistance and improved biological properties; (b) biological evaluations for specific applications, such as in glaucoma drainage devices, orthopedic implants, bone tissue regeneration, wound dressing, drug delivery systems, and antibacterial activity; and (c) in vitro and in vivo studies for cytotoxicity, genotoxicity, and cell viability. The interest in organosilicon materials stems from the fact that a vast array of these materials have complementary attributes that, when integrated appropriately with functional fillers and carefully controlled conditions, could be exploited either as polymeric Si-based composites or as organosilicon polymer-derived Si-based ceramic composites to tailor and optimize properties of the Si-based materials for various proposed applications.

Property-Activity Relationship of Black Phosphorus at the Nano-Bio Interface: From Molecules to Organisms.

As a novel member of the two-dimensional nanomaterial family, mono- or few-layer black phosphorus (BP) with direct bandgap and high charge carrier mobility is promising in many applications such as microelectronic devices, photoelectronic devices, energy technologies, and catalysis agents. Due to its benign elemental composition (phosphorus), large surface area, electronic/photonic performances, and chemical/biological activities, BP has also demonstrated a great potential in biomedical applications including biosensing, photothermal/photodynamic therapies, controlled drug releases, and antibacterial uses. The nature of the BP-bio interface is comprised of dynamic contacts between nanomaterials (NMs) and biological systems, where BP and the biological system interact. The physicochemical interactions at the nano-bio interface play a critical role in the biological effects of NMs. In this review, we discuss the interface in the context of BP as a nanomaterial and its unique physicochemical properties that may affect its biological effects. Herein, we comprehensively reviewed the recent studies on the interactions between BP and biomolecules, cells, and animals and summarized various cellular responses, inflammatory/immunological effects, as well as other biological outcomes of BP depending on its own physical properties, exposure routes, and biodistribution. In addition, we also discussed the environmental behaviors and potential risks on environmental organisms of BP. Based on accumulating knowledge on the BP-bio interfaces, this review also summarizes various safer-by-design strategies to change the physicochemical properties including chemical stability and nano-bio interactions, which are critical in tuning the biological behaviors of BP. The better understanding of the biological activity of BP at BP-bio interfaces and corresponding methods to overcome the challenges would promote its future exploration in terms of bringing this new nanomaterial to practical applications.

Wireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal models.

Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology.

Review of Endometriosis Diagnosis through Advances in Biomedical Engineering.

Endometriosis is characterized as the ectopic presence of endometrium in various locations within the abdominal cavity, such as the fallopian tube, the pouch of Douglas, the ovaries, outside the ovaries, and more. The inner lining of the uterus, endometrium, is a dynamic tissue that undergoes morphological and functional changes cyclically. The proliferation of endometrial cells during menstruation is influenced by increasing circulating estrogen levels. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity and hence, enhanced capacity to generate endometriosis. This chronic estrogen-dependent disease is characterized by the ectopic endometrial implant. The disorder occurs in 6%-10% of reproductive-aged women and in 35%-50% of women with pelvic pain and infertility. Currently, the preferred diagnostic methods are laparoscopic inspection by transvaginal ultrasound, MRI, and sensors. Diagnoses with transvaginal ultrasound have 92.7% sensitivity and 97% specificity in detecting endometriotic lesions. On average, MRI diagnoses of DIE have 74% sensitivity and 95% specificity. Lastly, chemical sensors have 91.7% sensitivity and 90.0% specificity in detecting endometriosis. The standard of care includes personalizing the treatment plan based on the individual's set of symptoms and their severity. Advances in biomedical engineering have aided professionals in personalizing the course of treatments as well as to increasing the quality of life of these patients through various therapies for managing pain. Because no one theory provides a full explanation for the manifestation of the disease, hormonal therapies, targeted therapeutics, and surgical options have emerged as elements of disease management. Clinicians are in the process of developing advanced pharmaceutical drugs with specific orphan target receptors of the ectopic tissue. Possible complications that accompany the condition include dyspareunia, hyperalgesia, infertility, and many others.

Tumor-on-a-chip platforms for assessing nanoparticle-based cancer therapy.

Cancer has become the most prevalent cause of deaths, placing a huge economic and healthcare burden worldwide. Nanoparticles (NPs), as a key component of nanomedicine, provide alternative options for promoting the efficacy of cancer therapy. Current conventional cancer models have limitations in predicting the effects of various cancer treatments. To overcome these limitations, biomimetic and novel 'tumor-on-a-chip' platforms have emerged with other innovative biomedical engineering methods that enable the evaluation of NP-based cancer therapy. In this review, we first describe cancer models for evaluation of NP-based cancer therapy techniques, and then present the latest advances in 'tumor-on-a-chip' platforms that can potentially facilitate clinical translation of NP-based cancer therapies.

Influence of quasi-spherical polarization on results of bioelectromagnetic studies.

One of the most interesting questions in bioelectromagnetic and compatibility studies is differences between results of experiments performed in different labs in "identical" conditions, especially in bioelectromagnetics studies. A reason of these differences may be due to differences in investigated objects, particularly in in vivo experiments. However, the author, as engineer, would like to focus the readers' attention on the technical aspects of exposure systems namely: presence and role of mutual interaction between the object under test and the exposure system, interaction between exposure objects, the role of polarization and the similarity of real-life exposure to those applied in experiments, etc. All these factors may change the results of experiments and lead to false conclusions.

Reduction of diabetic foot ulcer healing times through use of advanced treatment modalities.

Diabetic wounds are a major health care problem associated with delayed healing and high amputation rates. This review systematically evaluated newer wound care therapies for the treatment of diabetic wounds. More recent means of approaching diabetic foot ulcers include various dressings, off-loading shoes, and bioengineered skin constructs and growth factors. Electrical stimulation, phototherapy, electromagnetic fields, and shockwave therapy have been further proposed as potential treatments. A brief overview of these treatments is presented using peer-reviewed evidenced-based literature. A review of the literature demonstrated that treatment of diabetic wounds has focused on either prevention of the wounds in the form of off-loading shoes or adequate protective dressings or on direct treatment of wounds with bioengineered skin constructs, growth factors, or medical devices that accelerate wound healing. The authors' conclusion, following extensive literature review, is that although excellent national and international guidelines exist regarding suggested approaches to the treatment of the diabetic foot ulcer, there is no definitive or universal consensus on the choice of specific treatment modalities. The importance of optimizing comorbidities and the disease state, hemodynamics, local and peripheral skin and wound care, and metabolic challenges while reducing biological and bacterial burden and minimizing trauma remain the primary approach, followed by choice of the most appropriate treatment material or product.

Induced pluripotent stem cells for regenerative medicine.

With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies offer novel tools for the reprogramming, expansion, isolation, and differentiation of iPS cells. In this article, we review these bioengineering approaches for the derivation and manipulation of iPS cells and focus on their relevance to regenerative medicine.

Brain-computer interfaces for neurorehabilitation.

Brain-computer interfaces (BCIs) enable control of computers and other assistive devices, such as neuro-prostheses, which are used for communication, movement restoration, neuro-modulation, and muscle stimulation, by using only signals measured directly from the brain. A BCI creates a new output channel for the brain to a computer or a device. This requires retrieval of signals of interest from the brain, and its use for neuro-rehabilitation by means of interfacing the signals to a computerized device. Brain signals such as action potentials from single neurons or nerve fibers, extracellular local field potentials (LFPs), electrocorticograms, electroencephalogram and its components such as the event-related brain potentials, real-time functional magnetic resonance imaging, near-infrared spectroscopy, and magneto-encephalogram have been used. BCIs are envisaged to be useful for communication, control and self-regulation of brain function. BCIs employ neurofeedback to enable operant conditioning to allow the user to learn using it. Paralytic conditions arising from stroke or other diseases are being targeted for BCI application. Neurofeedback strategies ranging from sensory feedback to direct brain stimulation are being employed. Existing BCIs are limited in their throughput in terms of letters per minute or commands per minute, and need extensive training to use the BCI. Further, they can cause rapid fatigue due to use and have limited adaptability to changes in the patient's brain state. The challenge before BCI technology for neuro-rehabilitation today is to enable effective clinical use of BCIs with minimal effort to set up and operate.

[System biology and synthetic biology modify drug discovery and development]. / Biologie des systèmes et ingénierie biologique modifient la découverte et le développement des médicaments.

Life Sciences are built on observations. Right now, a more systemic approach allowing to integrate the different organizational levels in Biology is emerging. Such an approach uses a set of technologies and strategies allowing to build models that appear to be more and more predictive (omics, bioinformatics, integrative biology, computational biology…). Those models accelerate the rational development of new therapies avoiding an engineering based only on trials and errors. This approach both holistic and predictive radically modifies the discovery and development modalities used today in health industries. Moreover, because of the apparition of new jobs at the interface of disciplines, of private and public sectors and of life sciences and engineering sciences, this implies to rethink the training programs in both their contents and their pedagogical tools.

Addressing neurological disorders with neuromodulation.

Neurological disorders are becoming increasingly common in developed countries as a result of the aging population. In spite of medications, these disorders can result in progressive loss of function as well as chronic physical, cognitive, and emotional disability that ultimately places enormous emotional and economic on the patient, caretakers, and the society in general. Neuromodulation is emerging as a therapeutic option in these patients. Neuromodulation is a field, which involves implantable devices that allow for the reversible adjustable application of electrical, chemical, or biological agents to the central or peripheral nervous system with the objective of altering its functioning with the objective of achieving a therapeutic or clinically beneficial effect. It is a rapidly evolving field that brings together many different specialties in the fields of medicine, materials science, computer science and technology, biomedical, and neural engineering as well as the surgical or interventional specialties. It has multiple current and emerging indications, and an enormous potential for growth. The main challenges before it are in the need for effective collaboration between engineers, basic scientists, and clinicians to develop innovations that address specific problems resulting in new devices and clinical applications.

Chip-scale hermetic feedthroughs for implantable bionics.

Most implantable medical devices such as cochlear implants and visual prostheses require protection of the stimulating electronics. This is achieved by way of a hermetic feedthrough system which typically features three important attributes: biocompatibility with the human body, device hermeticity and density of feedthrough conductors. On the quest for building a visual neuroprosthesis, a high number of stimulating channels is required. This has encouraged new technologies with higher rates of production yield and further miniaturization. An Al(2)O(3) based feedthrough system has been developed comprising up to 20 platinum feedthroughs per square millimeter. Ceramics substrates are shown to have leak rates below 1 × 10(-12) atm × cc/s, thus exceeding the resolution limits of most commercially available leak detectors. A sheet resistance of 0.05 Ω can be achieved. This paper describes the design, fabrication process and hermeticity testing of high density feedthroughs for use in neuroprosthetic implants.

VLSI implementation of a template subtraction algorithm for real-time stimulus artifact rejection.

In this paper, we present very-large-scale integrated (VLSI) implementation of a template subtraction algorithm for stimulus artifact rejection (SAR) in real time with applicability to closed-loop neuroprostheses. The SAR algorithm is based upon an infinite impulse response (IIR) temporal filtering technique, which can be efficiently implemented in VLSI with reduced power consumption and silicon area. We demonstrate that initialization of the memory within the system architecture using the first recorded stimulus artifact significantly decreases system response time as compared to the case without memory initialization. Two sets of pre-recorded neural data from an Aplysia californica are used to simulate the functionality of the proposed VLSI architecture in AMS 0.35 microm complementary metal-oxide-semiconductor (CMOS) technology. Depending upon the reproducibility in the shape of stimulus artifacts in vivo, the system eliminates virtually all artifacts in real time and recovers the extracellular neural activity with microW-level power consumption from 1.5 V.

Engineering evaluation of the energy-storing orthosis FES gait system.

A system to restore walking in the vicinity of a wheelchair for people with paraplegia resulting from spinal cord injury is under development. The approach combines single channel surface electrical stimulation with an orthosis. The orthosis is spring loaded and contains a pneumatic system that stores energy during knee extension caused by quadriceps stimulation and transfers it to hip joint for hip extension. A laboratory version of the prototype of the gait system has been fabricated and engineering bench tests were performed. The paper presents the design of the wearable prototype and results of bench testing.

Empirical mode decomposition (EMD) analysis of HRV data from locally anesthetized patients.

Spectral analysis of Heart Rate Variability (HRV) is used for the assessment of cardiovascular autonomic control. In this study data driven adaptive technique Empirical Mode Decomposition (EMD) and the associated Hilbert spectrum has been used to evaluate the effect of local anesthesia on HRV parameters in a group of fourteen patients undergoing brachial plexus block (local anesthesia) using transarterial technique. The confidence limit for the stopping criteria was establish and the S value that gave the smallest squared deviation from the mean was considered optimal. The normalized amplitude Hilbert spectrum was used to calculate the error index associated with the instantaneous frequency. The amplitude and the frequency values were corrected in the region where the error was higher than twice the standard deviation. The Intrinsic Mode Function (IMF) components were assigned to the Low Frequency (LF) and the High Frequency (HF) part of the signal by making use of the center frequency and the standard deviation spectral extension estimated from the marginal spectrum of the IMF components. The analysis procedure was validated with the help of a simulated signal which consisted of two components in the LF and the HF region of the HRV signal with varying amplitude and frequency. The optimal range of the stopping criterion was found to be between 4 and 9 for the HRV data. The statistical analysis showed that the LF/HF amplitude ratio decreased within an hour of the application of the brachial plexus block compared to the values at the start of the procedure. These changes were observed in thirteen of the fourteen patients included in this study.