scholarly journals Advances in Implantable Optogenetic Technology for Cardiovascular Research and Medicine

2021 ◽  
Vol 12 ◽  
Author(s):  
Micah K. Madrid ◽  
Jaclyn A. Brennan ◽  
Rose T. Yin ◽  
Helen S. Knight ◽  
Igor R. Efimov

Optogenetic technology provides researchers with spatiotemporally precise tools for stimulation, sensing, and analysis of function in cells, tissues, and organs. These tools can offer low-energy and localized approaches due to the use of the transgenically expressed light gated cation channel Channelrhodopsin-2 (ChR2). While the field began with many neurobiological accomplishments it has also evolved exceptionally well in animal cardiac research, both in vitro and in vivo. Implantable optical devices are being extensively developed to study particular electrophysiological phenomena with the precise control that optogenetics provides. In this review, we highlight recent advances in novel implantable optogenetic devices and their feasibility in cardiac research. Furthermore, we also emphasize the difficulties in translating this technology toward clinical applications and discuss potential solutions for successful clinical translation.

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1288
Author(s):  
Wendy Dong ◽  
Boris Kantor

CRISPR/Cas technology has revolutionized the fields of the genome- and epigenome-editing by supplying unparalleled control over genomic sequences and expression. Lentiviral vector (LV) systems are one of the main delivery vehicles for the CRISPR/Cas systems due to (i) its ability to carry bulky and complex transgenes and (ii) sustain robust and long-term expression in a broad range of dividing and non-dividing cells in vitro and in vivo. It is thus reasonable that substantial effort has been allocated towards the development of the improved and optimized LV systems for effective and accurate gene-to-cell transfer of CRISPR/Cas tools. The main effort on that end has been put towards the improvement and optimization of the vector’s expression, development of integrase-deficient lentiviral vector (IDLV), aiming to minimize the risk of oncogenicity, toxicity, and pathogenicity, and enhancing manufacturing protocols for clinical applications required large-scale production. In this review, we will devote attention to (i) the basic biology of lentiviruses, and (ii) recent advances in the development of safer and more efficient CRISPR/Cas vector systems towards their use in preclinical and clinical applications. In addition, we will discuss in detail the recent progress in the repurposing of CRISPR/Cas systems related to base-editing and prime-editing applications.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Di Girolamo ◽  
M Appignani ◽  
N Furia ◽  
M Marini ◽  
P De Filippo ◽  
...  

Abstract Background Direct exposure of implantable cardioverter-defibrillators (ICDs) during radiotherapy is still considered potentially harmful, or even unsafe, by manufacturers and current recommendations. The effects of photon beams on ICDs are unpredictable, depending on multiple factors, and malfunctions may present during exposure. Purpose To evaluate transient ICD malfunctions by direct exposure to doses up to 10 Gy during low-energy RT, forty-three contemporary wireless-enabled ICDs, with at least 4 months to elective replacement indicator (ERI) were evaluated in a real-time in-vitro session in three different centres. Methods All ICDs had baseline interrogation. Single chamber devices were programmed to the VVI/40 mode and dual or triple chamber devices were programmed to the DDD/40 mode. Rate response function and antitachycardia therapies were disabled, with the ventricular tachycardia (VT)/ventricular fibrillation (VF) detection windows still active. A centring computed tomography was performed to build the corresponding treatment plan and the ICDs were blinded randomized to receive either 2-, 5- or 10-Gy exposure by a low photon-energy linear accelerator (6MV) in a homemade water phantom (600 MU/min). The effective dose received by the ICDs was randomly assessed by an in-vivo dosimetry. During radiotherapy, the ICDs were observed in a real-time session using manufacturer specific programmer, and device function (pacing, sensing, programmed parameters, arrhythmia detections) was recorder by the video camera in the bunker throughout the entire photon exposure. All ICDs had an interrogation session immediately after exposure. Results During radiotherapy course, almost all ICDs (93%) recorded major or minor transient electromagnetic interferences. On detail, sixteen ICDs (37.2%) reported atrial and/or ventricular oversensing, with base-rate-pacing inhibition and VT/VF detection. Twenty-four ICDs (55.8%) recorded non clinically relevant noise, and no detections were observed. Only three ICDs (7%) reported neither transient malfunction nor minor noise, withstanding direct radiation exposure. At immediate post-exposure interrogation, the ICDs that recorded major real-time malfunctions had VT/VF detections stored in the device memory. In none of the ICDs spontaneous changes in parameter settings were reported. Malfunctions occurred regardless of either 2-, 5- or 10-Gy photon beam exposure. Conclusions Transient electromagnetic interferences were observed in most of the contemporary ICDs during radiotherapy course, regardless of photon dose. To avoid potentially life-threatening ICD malfunctions such as pacing inhibition or inappropriate shock delivery, magnet application on the pocket site or ICD reprogramming to the asynchronous mode are still suggested in ICD patients ongoing even low energy radiotherapy exposure. Funding Acknowledgement Type of funding source: None


Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2980
Author(s):  
Pavel V. Melnikov ◽  
Anastasia Yu. Alexandrovskaya ◽  
Alina O. Naumova ◽  
Nadezhda M. Popova ◽  
Boris V. Spitsyn ◽  
...  

The development of different methods for tuning surface properties is currently of great interest. The presented work is devoted to the use of modified nanodiamonds to control the wetting and biological fouling of polymers using optical sensors as an example. We have shown that, depending on the type of modification and the amount of nanodiamonds, the surface of the same fluorinated polymer can have both bactericidal properties and, on the contrary, good adhesion to the biomaterial. The precise control of wetting and biofouling properties of the surface was achieved by the optimization of the modified nanodiamonds thermal anchoring conditions. In vitro and in vivo tests have shown that the fixation of amine functional groups leads to inhibition of biological activity, while the presence of a large number of polar groups of mixed composition (amide and acid chloride) promotes adhesion of the biomaterial and allows one to create a biosensor on-site. A comprehensive study made it possible to establish that in the first 5 days the observed biosensor response is provided by cells adhered to the surface due to the cell wall interaction. On the 7th day, the cells are fixed by means of the polysaccharide matrix, which provides much better retention on the surface and a noticeably greater response to substrate injections. Nevertheless, it is important to note that even 1.5 h of incubation is sufficient for the formation of the reliable bioreceptor on the surface with the modified nanodiamonds. The approach demonstrated in this work makes it possible to easily and quickly isolate the microbiome on the surface of the sensor and perform the necessary studies of its substrate specificity or resistance to toxic effects.


2021 ◽  
Vol 22 (17) ◽  
pp. 9517
Author(s):  
Gianluca Testa ◽  
Giorgia Di Benedetto ◽  
Fabiana Passaro

The adult human heart can only adapt to heart diseases by starting a myocardial remodeling process to compensate for the loss of functional cardiomyocytes, which ultimately develop into heart failure. In recent decades, the evolution of new strategies to regenerate the injured myocardium based on cellular reprogramming represents a revolutionary new paradigm for cardiac repair by targeting some key signaling molecules governing cardiac cell fate plasticity. While the indirect reprogramming routes require an in vitro engineered 3D tissue to be transplanted in vivo, the direct cardiac reprogramming would allow the administration of reprogramming factors directly in situ, thus holding great potential as in vivo treatment for clinical applications. In this framework, cellular reprogramming in partnership with nanotechnologies and bioengineering will offer new perspectives in the field of cardiovascular research for disease modeling, drug screening, and tissue engineering applications. In this review, we will summarize the recent progress in developing innovative therapeutic strategies based on manipulating cardiac cell fate plasticity in combination with bioengineering and nanotechnology-based approaches for targeting the failing heart.


2021 ◽  
Vol 12 ◽  
Author(s):  
Josanne S. de Maar ◽  
Charis Rousou ◽  
Benjamin van Elburg ◽  
Hendrik J. Vos ◽  
Guillaume P.R. Lajoinie ◽  
...  

Chemotherapy efficacy is often reduced by insufficient drug uptake in tumor cells. The combination of ultrasound and microbubbles (USMB) has been shown to improve drug delivery and to enhance the efficacy of several drugs in vitro and in vivo, through effects collectively known as sonopermeation. However, clinical translation of USMB therapy is hampered by the large variety of (non-clinical) US set-ups and US parameters that are used in these studies, which are not easily translated to clinical practice. In order to facilitate clinical translation, the aim of this study was to prove that USMB therapy using a clinical ultrasound system (Philips iU22) in combination with clinically approved microbubbles (SonoVue) leads to efficient in vitro sonopermeation. To this end, we measured the efficacy of USMB therapy for different US probes (S5-1, C5-1 and C9-4) and US parameters in FaDu cells. The US probe with the lowest central frequency (i.e. 1.6 MHz for S5-1) showed the highest USMB-induced intracellular uptake of the fluorescent dye SYTOX™ Green (SG). These SG uptake levels were comparable to or even higher than those obtained with a custom-built US system with optimized US parameters. Moreover, USMB therapy with both the clinical and the custom-built US system increased the cytotoxicity of the hydrophilic drug bleomycin. Our results demonstrate that a clinical US system can be used to perform USMB therapy as efficiently as a single-element transducer set-up with optimized US parameters. Therefore, future trials could be based on these clinical US systems, including validated US parameters, in order to accelerate successful translation of USMB therapy.


Author(s):  
Sophia M Mavris ◽  
Laura M Hansen

Abstract The field of tissue engineering has been continuously evolving since its inception over three decades ago with numerous new advancements in biomaterials and cell sources and widening applications to most tissues in the body. Despite the substantial promise and great opportunities for the advancement of current medical therapies and procedures, the field has yet to capture wide clinical translation due to some remaining challenges, including oxygen availability within constructs, both in vitro and in vivo. While this insufficiency of nutrients, specifically oxygen, is a limitation within the current frameworks of this field, the literature shows promise in new technological advances to efficiently provide adequate delivery of nutrients to cells. This review attempts to capture the most recent advances in the field of oxygen transport in hydrogel-based tissue engineering, including a comparison of current research as it pertains to the modeling, sensing, and optimization of oxygen within hydrogel constructs as well as new technological innovations to overcome traditional diffusion-based limitations. The application of these findings can further the advancement and development of better hydrogel-based tissue engineered constructs for future clinical translation and adoption.


Author(s):  
Shawn C. Oppegard ◽  
David T. Eddington

Oxygen is a key modulator of many cellular pathways and plays an important role in a number of cellular behaviors. The hypoxic inducible factor 1α (HIF-1α) is often considered the master regulator of the cellular response to oxygen tension (1). HIF-1α is a transcription factor involved in angiogenesis, glucose transport and glycolysis, apoptosis, migration, and differentiation, among many other functions (2). Unfortunately devices permitting in vitro oxygen modulation fail to meet the needs of biomedical research due to the inability to effectively mimic conditions found in vivo. The gold standard for hypoxia work is the hypoxic chamber, but the tool requires hours for equilibration and is not effective at generating very low oxygen levels (3). As an example demonstrating this disadvantage, cancer tumor oxygenation can change in the span of minutes (4). Intermittent hypoxia, or the changing of oxygen over time, has been shown to be important in heart attack, stroke, and sleep apnea as well. Other microfluidic approaches, although offering more oxygen control, are often difficult to disseminate to other labs due to the requirement of specialized methods and equipment for their operation. In this work, a microfabricated technology has been developed to grant precise control the temporal and spatial oxygen concentration exposed to both cell monolayers in the multiwell plate as well as with 3-D cell-seeded constructs. The concept is adaptable to both pre-established and novel experiments depending on the needs of the researcher. The devices are simple to use and require minimal additional equipment beyond what is available to a standard cell culture lab.


2019 ◽  
Vol 41 (25) ◽  
pp. 2405-2408 ◽  
Author(s):  
Filippo Perbellini ◽  
Thomas Thum

Abstract Heart function relies on the interplay of several specialized cell types and a precisely regulated network of chemical and mechanical stimuli. Over the last few decades, this complexity has often been undervalued and progress in translational cardiovascular research has been significantly hindered by the lack of appropriate research models. The data collected are often oversimplified and these make the translation of results from the laboratory to clinical trials challenging and occasionally misleading. Living myocardial slices are ultrathin (100–400μm) sections of living cardiac tissue that maintain the native multicellularity, architecture, and structure of the heart and can provide information at a cellular/subcellular level. They overcome most of the limitations that affect other in vitro models and they can be prepared from human specimens, proving a clinically relevant multicellular human model for translational cardiovascular research. The publication of a reproducible protocol, and the rapid progress in methodological and technological discoveries which prevent significant structural and functional changes associated with chronic in vitro culture, has overcome the last barrier for the in vitro use of this human multicellular preparations. This technology can bridge the gap between in vitro and in vivo human studies and has the potential to revolutionize translational research approaches.


Chemosensors ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 46 ◽  
Author(s):  
Ishtiaq Ahmed ◽  
Zain Akram ◽  
Mohammed Bule ◽  
Hafiz Iqbal

A micro-level technique so-called “microfluidic technology or simply microfluidic” has gained a special place as a powerful tool in bioengineering and biomedical engineering research due to its core advantages in modern science and engineering. Microfluidic technology has played a substantial role in numerous applications with special reference to bioscience, biomedical and biotechnological research. It has facilitated noteworthy development in various sectors of bio-research and upsurges the efficacy of research at the molecular level, in recent years. Microfluidic technology can manipulate sample volumes with precise control outside cellular microenvironment, at micro-level. Thus, enable the reduction of discrepancies between in vivo and in vitro environments and reduce the overall reaction time and cost. In this review, we discuss various integrations of microfluidic technologies into biotechnology and its paradigmatic significance in bio-research, supporting mechanical and chemical in vitro cellular microenvironment. Furthermore, specific innovations related to the application of microfluidics to advance microbial life, solitary and co-cultures along with a multiple-type cell culturing, cellular communications, cellular interactions, and population dynamics are also discussed.


Circulation ◽  
1991 ◽  
Vol 83 (1) ◽  
pp. 279-293 ◽  
Author(s):  
R Lemery ◽  
T K Leung ◽  
E Lavallée ◽  
A Girard ◽  
M Talajic ◽  
...  

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