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Optic nerve intraneural stimulation allows selective visual cortex activation

Retinal prostheses have been developed to restore a functional form of vision in patients affected by outer retinal layer dystrophies. Other approaches, namely optic nerve, thalamic, and cortical prostheses are under investigation to expand this toolbox both as clinical devices and as tools for fundamental research. Optic nerve stimulation is attractive since it bypasses the entire retinal network and directly activates nerve fibers. At the same time, it still takes advantage of the high-level information processing occurring downstream in the visual cortex. Here we show that a new intraneural electrode array (OpticSELINE) is effective in inducing the activation of the visual cortex upon electrical stimulation of the optic nerve. We also demonstrate that intraneural optic nerve stimulation induces selective cortical activation patterns depending on the stimulating electrode, thus suggesting that the OpticSELINE possesses spatial selectivity in fiber stimulation. In conclusion, the OpticSELINE can be used both as visual prosthesis for blind patients and as tool to further investigate the effect of the electrical stimulation in the visual system.

bioengineering

Bootstrapping EEG-based auditory attention detection systems: boundary conditions for background noise and speaker positions

ObjectiveA listeners neural responses can be decoded to identify the speaker the person is attending to in a cocktail party environment. Such auditory attention detection methods have the potential to provide noise suppression algorithms in hearing devices with information about the listeners attention. A challenge is the effect of noise and other acoustic conditions that can reduce the attention detection accuracy. Specifically, noise can impact the ability of the person to segregate the sound sources and perform selective attention, as well as the external signal processing necessary to decode the attention effectively. The aim of this work is to systematically analyze the effect of noise level and speaker position on attention decoding accuracy.\n\nApproach28 subjects participated in the experiment. Auditory stimuli consisted of stories narrated by different speakers from 2 different locations, along with surrounding multi-talker background babble. EEG signals of the subjects were recorded while they focused on one story and ignored the other. The strength of the babble noise as well as the spatial separation between the two speakers were varied between presentations. Spatio-temporal decoders were trained for each subject, and applied to decode attention of the subjects from every 30s segment of data. Behavioral speech recognition thresholds were obtained for the different speaker separations.\n\nMain resultsBoth the background noise level and the angular separation between speakers affected attention decoding accuracy. Remarkably, attention decoding performance was seen to increase with the inclusion of moderate background noise (versus no noise), while across the different noise conditions performance dropped significantly with increasing noise level. We also observed that decoding accuracy improved with increasing speaker separation, exhibiting the advantage of spatial release from masking. Furthermore, the effect of speaker separation on the decoding accuracy became stronger when the background noise level increased. A significant correlation between speech intelligibility and attention decoding accuracy was found across conditions.\n\nSignificanceThis work shows how the background noise level and relative positions of competing talkers impact attention decoding accuracy. It indicates in which circumstances a neuro-steered noise suppression system may need to operate, in function of acoustic conditions. It also indicates the boundary conditions for the operation of EEG-based attention detection systems in neuro-steered hearing prostheses.\n\nIndex TermsAuditory attention detection, EEG processing, neuro-steered auditory prostheses, brain-computer interface, cocktail party, acoustic conditions.\n\nThe work is funded by KU Leuven Special Research Fund C14/16/057 and OT/14/119, FWO project nrs. 1.5.123.16N and G0A4918N, the ERC (637424) under the European Unions Horizon 2020 research and innovation programme, and a research gift of Starkey Hearing Technologies. The scientific responsibility is assumed by its authors.

bioengineering

Loading of piperlongumine to liposomes after complexation with β-cyclodextrin and its effect on viability of colon and prostate cancer cells

Use of nano carriers to treat cancer is attractive due to their advantages such as the sustained release of drugs and ability to target specific regions of the body where treatment is needed. However, loading water insoluble chemotherapeutic drugs into liposomes is challenging. In this study, we developed a method to encapsulate water-insoluble drug (piperlongumine) in liposomes by complexing piperlongumine with {beta}-Cyclodextrin. Liposomes encapsulated with piperlongumine incubated with COLO 205 and PC-3 cell lines and demonstrated that viability of COLO 205 and PC-3 cells decreases to 7% and 41% respectively when the piperlongumine concentration is at 20 M.

bioengineering

Stability-normalised walking speed: a new approach for human gait perturbation research

In gait stability research, neither self-selected walking speeds, nor the same prescribed walking speed for all participants, guarantee equivalent gait stability among participants. Furthermore, these options may differentially affect the response to different gait perturbations, which is problematic when comparing groups with different capacities. We present a method for decreasing inter-individual differences in gait stability by adjusting walking speed to equivalent margins of stability (MoS). Eighteen healthy adults walked on a split-belt treadmill for two-minute bouts at 0.4m/s up to 1.8m/s in 0.2m/s intervals. The stability-normalised walking speed (MoS=0.05m) was calculated using the mean MoS at touchdown of the final 10 steps of each speed. Participants then walked for three minutes at this speed and were subsequently exposed to a treadmill belt acceleration perturbation. A further 12 healthy adults were exposed to the same perturbation while walking at 1.3m/s: the average of the previous group. Large ranges in MoS were observed during the prescribed speeds (6-10cm across speeds) and walking speed significantly (P<0.001) affected MoS. The stability-normalised walking speeds resulted in MoS equal or very close to the desired 0.05m and reduced between-participant variability in MoS. The second group of participants walking at 1.3m/s had greater inter-individual variation in MoS during both unperturbed and perturbed walking compared to 12 sex, height and leg length-matched participants from the stability-normalised walking speed group. The current method decreases inter-individual differences in gait stability which may be beneficial for gait perturbation and stability research, in particular for studies on populations with different locomotor capacities.

bioengineering

Polymeric perfluoropentane nanoemulsions are a versatile platform for ultrasonic drug uncaging

Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness, as well as the relatively broad drug spatial distribution that is achievable with selective arterial catheterization. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle enable noninvasive targeted drug delivery, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs to meet these needs, beyond a few niche applications. Here, we directly address all of those challenges and fully develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted drug delivery with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that hew to clinical standards and yield stable and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, as a new potential clinical application for these nanoemulsions, we exhibit their in vivo efficacy and performance for cardiovascular applications, by achieving local vasodilation in the highest flow vessel of the body, the aorta. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for effective noninvasive ultrasonic drug uncaging for myriad targets in the brain and body.

bioengineering

Improved localizers and anatomical images to enable phosphorus magnetic resonance spectroscopy of liver metastasis at 7T

Phosphorus spectroscopy (31P) at 7T (300 MHz) enables clinically-relevant spatial resolutions and time scales with high potential for monitoring response to cancer treatment. However, at 7T collecting a radiological-grade anatomical image of the liver--which is required for performing localized 31P spectroscopy--presents a challenge. Unlike lower field-strength scanners, there is no body coil in the bore of the 7T and despite inadequate penetration depth (<10 cm), surface coils are the current state-of-the-art for acquiring anatomical (1H) images. Therefore, thus far, high field 31P spectroscopy has been limited to diffuse liver disease. However, the use of antennas enable improved penetration depths at 300 MHz, and when combined with parallel transmit, can enable body imaging at 7T. We have developed a protocol for imaging liver metastases of patients using parallel transmit and 31P spectroscopy at 7T. We used a custom-made liver coil consisting of eight 30-cm dipole antennas tuned to the proton (300 MHz) frequency, and two partially overlapping 20-cm-diameter loops tuned for 31P (120 MHz). The field of view afforded by the two antennas underneath the 31P loops is not sufficient to image the complete boundaries of the liver for chemical shift imaging (CSI) planning and region-of-interest-based B0 shimming. The liver and full axial slice of the abdomen was imaged with eight transmit/receive antennas using parallel transmit B1-shimming to overcome image voids. Through the use of antennas we overcome the challenges for multi-parametric body imaging, and can begin to explore the possibility of monitoring the response of patients with liver metastasis to cancer treatments.\n\nABBREVIATIONS

bioengineering

Voltage-sensitive dye delivery through the blood brain barrier using adenosine receptor agonist Regadenoson

Optical imaging of brain activity has mostly employed genetically manipulated mice, which cannot be translated to clinical human usage. Observation of brain activity directly is challenging due to difficulty in delivering dyes and other agents through the blood brain barrier (BBB). Using fluorescence imaging, we have demonstrated the feasibility of delivering the near-infrared voltage-sensitive dye (VSD) IR-780 perchlorate to the brain tissue through pharmacological techniques, via an adenosine agonist (Regadenoson). Comparison of VSD fluorescence of mouse brains without and with Regadenoson showed significantly increased residence time of the fluorescence signal in the latter case, indicative of VSD diffusion into the brain tissue. Dose and timing of Regadenoson were varied to optimize BBB permeability for VSD delivery.

bioengineering

Site-specific PEGylation crosslinking of L-asparaginase subunits to improve its therapeutic efficiency

L-Asparaginase is an enzyme successfully being used in the treatment of acute lymphoblastic leukemia, acute myeloid leukemia, and non-Hodgkins lymphoma. However, some disadvantages still limit its full application potential, e.g., allergic reactions, pancreatitis, and blood clotting impairment. Therefore, much effort has been directed at improving its performance. A popular strategy is to randomly conjugate L-asparaginase with mono-methoxy polyethylene glycol, which became a commercial FDA approved formulation widely used in recent years. To improve this formulation by PEGylation, herein we performed cysteine-directed site-specific conjugation of the four L-asparaginase subunits to prevent dissociation-induced loss of activity. The conjugation sites were selected at surface-exposed positions on the protein to avoid affecting the catalytic activity. Three conjugates were obtained using different linear PEGs of 1000, 2000, and 5000 g/mol, with physical properties ranging from a semi-solid gel to a fully soluble state. The soluble-conjugate exhibited higher catalytic activity than the non-conjugated mutant, and the same activity than the native enzyme. Site-specific crosslinking of the L-asparaginase subunits produced a higher molecular weight conjugate compared to the native tetrameric enzyme. This strategy might improve L-asparaginase efficiency for leukemia treatment by reducing glomerular filtration due to the increase in hydrodynamic size thus extending half-live, while at the same time retaining full catalytic activity.

bioengineering

Remote manipulation of magnetic nanoparticles using magnetic field gradient to promote cancer cell death

The manipulation of magnetic nanoparticles (MNPs) using an external magnetic field, has been demonstrated to be useful in various biomedical applications. Some techniques have evolved utilizing this non-invasive external stimulus but the scientific community widely adopts few, and there is an excellent potential for more novel methods. The primary focus of this study is on understanding the manipulation of MNPs by a time-varying static magnetic field and how this can be used, at different frequencies and displacement, to manipulate cellular function. Here we explore, using numerical modeling, the physical mechanism which underlies this kind of manipulation, and we discuss potential improvements which would enhance such manipulation with its use in biomedical applications, i.e., increasing the MNP response by improving the field parameters. From our observations and other related studies, we infer that such manipulation depends mostly on the magnetic field gradient, the magnetic susceptibility and size of the MNPs, the magnet array oscillating frequency, the viscosity of the medium surrounding MNPs, and the distance between the magnetic field source and the MNPs. Additionally, we demonstrate cytotoxicity in neuroblastoma (SH-SY5Y) and hepatocellular carcinoma (HepG2) cells in vitro. This was induced by incubation with MNPs, followed by exposure to a magnetic field gradient, physically oscillating at various frequencies and displacement amplitudes. Even though this technique reliably produces MNP endocytosis and/or cytotoxicity, a better biophysical understanding is required to develop the mechanism used for this precision manipulation of MNPs, in vitro.

bioengineering

Robotic selection for the rapid development of stable CHO cell lines for HIV vaccine for production

The production of envelope glycoproteins (Envs) for use as HIV vaccines is challenging. The yield of Envs expressed in stable Chinese Hamster Ovary (CHO) cell lines is typically 10-100 fold lower than other glycoproteins of pharmaceutical interest. Moreover, Envs produced in CHO cells are typically enriched for sialic acid containing glycans compared to virus associated Envs that possess mainly high-mannose carbohydrates. This difference alters the net charge and biophysical properties of Envs and impacts their antigenic structure. Here we employ a novel gene-edited CHO cell line (MGAT1- CHO) to address the problems of low expression, high sialic acid content, and poor antigenic structure. We demonstrate that stable cell lines expressing high levels of gp120, potentially suitable for biopharmaceutical production can be created using the MGAT1- CHO cell line. We also show that the efficiency of this process can be greatly improved with robotic selection. Finally, we describe a MGAT1- CHO cell line expressing A244-rgp120 that exhibits improved binding of three major families of bN-mAbs compared to Envs produced in normal CHO cells. The new strategy described has the potential to eliminate the bottleneck in HIV vaccine development that has limited the field for more than 25 years.

bioengineering

The Effects of Different Vibration Frequencies, Amplitudes and Contraction Levels on Lower Limb Muscles during Graded Isometric Contractions Superimposed on Whole Body Vibration Stimulation

BackgroundIndirect vibration stimulation i.e. whole body vibration or upper limb vibration, has been suggested increasingly as an effective exercise intervention for sports and rehabilitation applications. However, there is a lack of evidence regarding the effects of whole body vibration (WBV) stimulation superimposed to graded isometric contractions superimposed on. For this scope, we investigated the effects of WBV superimposed to graded isometric contractions in the lower limbs on muscle activation. We also assessed the agonist-antagonist co-activation during this type of exercise.\n\nTwelve healthy volunteers were exposed to WBV superimposed to graded isometric contractions, at 20, 40, 60, 80 and 100% of the maximum voluntary contractions (V) or just isometric contractions performed on a custom designed horizontal leg press Control (C). Tested stimulation consisted of 30Hzand 50Hz frequencies and 0.5mm and 1.5mm amplitudes. Surface electromyographic activity of Vastus Lateralis (VL), Vastus Medialis (VM) and Biceps Femoris (BF) were measured during V and C conditions. Co-contraction activity of agonist-antagonist muscles was also quantified. The trials were performed in random order.\n\nResultsBoth the prime mover, (VL) and the antagonist, (BF) displayed significantly higher (P < 0.05) EMG activity with the V than the C condition. For both the VL and BF, the increase in mean EMGrms values depended on the frequency, amplitude and muscle contraction level with 50Hz-0.5mm stimulation inducing the largest neuromuscular activity. 50Hz-0.5mm V condition also led to co-activation ratios significantly (P< 0.05) higher at 40, 80 and 100% of MVC than the C condition.\n\nConclusionsOur results show that the isometric contraction superimposed on vibration stimulation leads to higher neuromuscular activity compared to isometric contraction alone in the lower limbs. Compared to the control condition, the vibratory stimulation leads to higher agonist-antagonist co-activation of the muscles around the knee joint in all vibration conditions and effort levels. The combination of vibration magnitude (frequency and amplitude) and the level of muscle contraction affect neuromuscular activity rather than vibration frequency alone. Results of this study suggest that more parameters need to be taken into consideration when designing vibration exercise programs for sports and rehabilitation purposes.

bioengineering

Can the presence of neural probes be neglected in computational modeling of extracellular potentials?

AbstractO_ST_ABSObjectiveC_ST_ABSMechanistic modeling of neurons is an essential component of computational neuroscience that enables scientists to simulate, explain, and explore neural activity. The conventional approach to simulation of extracellular neural recordings first computes transmembrane currents using the cable equation and then sums their contribution to model the extracellular potential. This two-step approach relies on the assumption that the extracellular space is an infinite and homogeneous conductive medium, while measurements are performed using neural probes. The main purpose of this paper is to assess to what extent the presence of the neural probes of varying shape and size impacts the extracellular field and how to correct for them.\n\nApproachWe apply a detailed modeling framework allowing explicit representation of the neuron and the probe to study the effect of the probes and thereby estimate the effect of ignoring it. We use meshes with simplified neurons and different types of probe and compare the extracellular action potentials with and without the probe in the extracellular space. We then compare various solutions to account for the probes presence and introduce an efficient probe correction method to include the probe effect in modeling of extracellular potentials.\n\nMain resultsOur computations show that microwires hardly influence the extracellular electric field and their effect can therefore be ignored. In contrast, Multi-Electrode Arrays (MEAs) significantly affect the extracellular field by magnifying the recorded potential. While MEAs behave similarly to infinite insulated planes, we find that their effect strongly depends on the neuron-probe alignment and probe orientation.\n\nSignificanceIgnoring the probe effect might be deleterious in some applications, such as neural localization and parameterization of neural models from extracellular recordings. Moreover, the presence of the probe can improve the interpretation of extracellular recordings, by providing a more accurate estimation of the extracellular potential generated by neuronal models.

bioengineering

Boosting heterologous protein production yield by adjusting global nitrogen and carbon metabolic regulatory networks in Bacillus subtilis

Bacillus subtilis is extensively applied as a microorganism for the high-level production of heterologous proteins. Traditional strategies for increasing the productivity of this microbial cell factory generally focused on the targeted modification of rate-limiting components or steps. However, the longstanding problems of limited productivity of the expression host, metabolic burden and non-optimal nutrient intake, have not yet been solved to achieve production strain improvements. To tackle this problem, we systematically rewired the regulatory networks of the global nitrogen and carbon metabolism by random mutagenesis of the pleiotropic transcriptional regulators CodY and CcpA, to allow for optimal nutrient intake, translating into significantly higher heterologous protein production yields. Using a {beta}-galactosidase expression and screening system and consecutive rounds of mutagenesis, we identified mutant variants of both CcpA and CodY that in conjunction increased production levels up to 290%. RNA-Seq and electrophoretic gel mobility shift analyses showed that amino acid substitutions within the DNA-binding domains altered the overall binding specificity and regulatory activity of the two transcription factors. Consequently, fine-tuning of the central metabolic pathways allowed for enhanced protein production levels. The improved cell factory capacity was further demonstrated by the successfully increased overexpression of GFP, xylanase and a peptidase in the double mutant strain.\n\nHighlightsO_LIThe global transcription machinery engineering (gTME) technique was applied to build mutational libraries of the pleiotropic regulators CodY and CcpA in Bacillus subtilis\nC_LIO_LISpecific point mutations within the DNA-binding domains of CodY and CcpA elicited alterations of the binding specificity and regulatory activity\nC_LIO_LIChanges in the transcriptome evoked the reprogramming of networks that gear the carbon and nitrogen metabolism\nC_LIO_LIThe rewired metabolic networks provided a higher building block capacity for heterologous protein production by adjusting the nutrient uptake and channeling its utilization for protein overexpression\nC_LI

bioengineering

Simulating Contact Using the Elastic Foundation Algorithm in OpenSim

Modeling joint contact is necessary to test many questions using simulation paradigms, but this portion of OpenSim is not well understood. The purpose of this study was to provide a guide for implementing a validated elastic foundation contact model in OpenSim. First, the load-displacement properties of a stainless steel ball bearing and ultra high molecular weight polyethylene (UHMWPE) slab were recorded during a controlled physical experiment. These geometries were imported and into OpenSim and contact mechanics were modeled with the on-board elastic foundation algorithm. Particle swarm optimization was performed to determine the elastic foundation model stiffness (2.14x1011 {+/-} 6.81x109 N/m) and dissipation constants (0.999 {+/-} 0.003). Estimations of contact forces compared favorably with blinded experimental data (root mean square error: 87.58 {+/-} 1.57 N). Last, total knee replacement geometry was used to perform a sensitivity analysis of material stiffness and mesh density with regard to penetration depth and computational time. These simulations demonstrated that material stiffnesses between 1011 and 1012 N/m resulted in realistic penetrations (< 0.15mm) when subjected to 981N loads. Material stiffnesses between 1013 and 1015 N/m increased computation time by factors of 12-23. This study shows the utility of performing a simple physical experiment to tune model parameters when physical components of orthopaedic implants are not available to the researcher. It also demonstrates the efficacy of employing the on-board elastic foundation algorithm to create realistic simulations of contact between orthopaedic implants.

bioengineering

A high-density carbon fiber neural recording array technology

Abstract.Objective: Microwire and Utah-style neural recording arrays are the predominant devices used for cortical neural recording, but the implanted electrodes cause a significant adverse biological response and suffer from well-studied performance degradation. Recent work has demonstrated that carbon fiber electrodes do not elicit this same adverse response, but these existing designs are not practically scalable to hundreds or thousands of recording sites. We present technology that overcomes these issues while additionally providing fine electrode pitch for spatial oversampling.\n\nApproach: We present a 32-channel carbon fiber monofilament-based intracortical neural recording array fabricated through a combination of bulk silicon microfabrication processing and microassembly. This device represents the first truly two-dimensional carbon fiber neural recording array. The density, channel count, and size scale of this array are enabled by an out-of-plane microassembly technique in which individual fibers are inserted through metallized and isotropically conductive adhesive-filled holes in an oxide-passivated microfabricated silicon substrate.\n\nMain results: Five-micron diameter fibers are spaced at a pitch of 38 microns, four times denser than state of the art one-dimensional arrays. The fine diameter of the carbon fibers affords both minimal cross-section and nearly three orders of magnitude greater lateral compliance than standard tungsten microwires. Typical 1 kHz impedances are on the order of hundreds of kiloohms, and successful in vivo recording is demonstrated in the motor cortex of a rat. 22 total units are recorded on 20 channels, with unit SNR ranging from 0.85 to 4.2.\n\nSignificance: This is the highest density microwire-style electrode array to date, and this fabrication technique is scalable to a larger number of electrodes and allows for the potential future integration of microelectronics. Large-scale carbon fiber neural recording arrays are a promising technology for reducing the inflammatory response and increasing the information density, particularly in neural recording applications where microwire arrays are already used.

bioengineering

Prenatal growth map of the mouse knee joint by mean of deformable registration technique

Joint morphogenesis is the process during which distinct and functional joint shapes emerge during pre- and post-natal joint development. In this study, a repeatable semi-automatic protocol capable of providing a 3D realistic developmental map of the prenatal mouse knee joint was designed by combining Optical Projection Tomography imaging (OPT) and a deformable registration algorithm (Sheffield Image Registration toolkit, ShIRT). Eleven left limbs of healthy murine embryos were scanned with OPT (voxel size: 14.63[1/4]m) at two different stages of development: Theiler stage (TS) 23 (approximately 14.5 embryonic days) and 24 (approximately 15.5 embryonic days). One TS23 limb was used to evaluate the precision of the displacement predictions for this specific case. The remaining limbs were then used to estimate Developmental Tibia and Femur Maps. Acceptable uncertainties of the displacement predictions were found for both epiphyses (between 0.7 and 1.4 m, along all directions and anatomical sites) for nodal spacing of 1 voxel. The protocol was found to be reproducible with maximum Modified Housdorff Distance differences equal to 1.9 m and 1.5 m for the tibial and femoral epiphyses respectively. The effect of the initial shape of the rudiment affected the developmental maps by 21.7 m and 21.9 m for the tibial and femoral epiphyses respectively, which correspond to 1.4 and 1.5 times the voxel size. To conclude, this study proposes a repeatable semi-automatic protocol capable of providing mean 3D realistic developmental map of a developing rudiment allowing researchers to study how growth and adaptation are directed by biological and mechanobiological factors.

bioengineering

Understanding the impact of crosslinked PCL/PEG/GelMA electrospun nanofibers on bactericidal activity

Herein, we report the design of electrospun ultrathin fibers based on polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential bactericidal activity against three different bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Our developed scaffolds were thus able to significantly reduce gram-positive, negative, and MRSA bacteria. Furthermore, we performed a series of study for better mechanistic understanding of the scaffolds bactericidal activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. In summary, we have demonstrated the design and generation of electrospun fibers with improved hydrophilicity and efficient bactericidal activity without the association of any antibiotics.

bioengineering

Gold Nanoprisms as Optical Coherence Tomography Contrast Agents in the Second Near Infrared Window for Enhanced Angiography in Live Animals

Optical coherence tomography angiography (OCTA) is an important tool for investigating vascular networks and microcirculation in living tissue. Traditional OCTA detects blood vessels via intravascular dynamic scattering signals derived from the movements of red blood cells (RBCs). However, the low hematocrit and long latency between RBCs in capillaries makes these OCTA signals discontinuous, leading to incomplete mapping of the vascular networks. OCTA imaging of microvascular circulation is particularly challenging in tumors due to the abnormally slow blood flow in angiogenic tumor vessels and strong attenuation of light by tumor tissue. Here we demonstrate in vivo that gold nanoprisms (GNPRs) can be used as OCT contrast agents working in the second near infrared window, significantly enhancing the dynamic scattering signals in microvessels and improving the sensitivity of OCTA in skin tissue and melanoma tumors in live mice. This is the first demonstration that nanoparticle-based OCT contrast agent work in vivo in the second near infrared window, which allows deeper imaging depth by OCT. With GNPRs as contrast agents, the post-injection OCT angiograms showed 41% and 59% more microvasculature than pre-injection angiograms in healthy mouse skin and melanoma tumors, respectively. By enabling better characterization of microvascular circulation in vivo, GNPR-enhanced OCTA could lead to better understanding of vascular functions during pathological conditions, more accurate measurements of therapeutic response, and improved patient prognoses.

bioengineering