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Accurate monitoring of microvasculature functioning enables early detection of diseases related to skin microcirculation disorders. The efficient capillaroscopy approach is to visualize and assess blood microcirculation exactly in the inflamed areas. In this paper, we propose an exoscope concept for non-invasive imaging of capillary network in skin arbitrary area. The main design aspects are briefly discussed. The described concept has been approved experimentally by in vivo mapping and analysis of microvessels in human skin.

Needle-free jet injection is a drug delivery technique that uses a high–speed stream of liquid drug to penetrate skin and deliver the liquid into underlying tissues. The shape of the nozzle through which the jet is created has an impact on jet shape, and on the shape of the resulting tissue incision. In some cases, jet injection through the skin can result in the release of blood from the capillary network. Here, we use modelling and measurement techniques to investigate the dependence of jet injection on the nozzle shape with a voice-coil actuated jet injector. We predict the shape and speed of fluid jets from a variety of nozzle designs, capture high speed video of the jet shape in air from four custom-made nozzles, and evaluate the potential of each nozzle to disrupt capillaries in skin by injecting tissue marking dye into post-mortem porcine tissue.

Development of the technique for constructing three-dimensional tissues having an internal perfusable vascular network is a challenging issue. In this study, we developed a method for realizing it. Firstly, we prepared hydrogel fiber of about 200 μm in diameter and HepG2 cell-enclosing microcapsules of about 500 μm in diameter from alginate derivative through horseradish peroxidase-catalyzed hydrogelation. After covering the surfaces of the hydrogel constructs with human umbilical vein endothelial cells (HUVECs), we assembled them in collagen gel. The endothelial cells on the hydrogel constructs sprouted and spontaneously formed a network connecting the hydrogel constructs with each other in the collagen gel. Then the microcapsules and the fiber were degraded using degrading enzymes. The medium introduced into the spontaneously formed capillary network flowed around the individual spherical tissues.

This work presents experiments considering a hybrid and multiscale model of avascular and vascular tumor growth. The model uses phase-field equations to describe the tumor and vascular growth, and reaction-diffusion equations for the distribution of nutrients and angiogenic factors. We use the high-performance framework PetIGA based on Isogeometric Analysis to implement the model. Our numerical experiments show that the model is able to represent the capillary network formation and its ability to represent specific tumor growth configurations.

In this study, we developed a microfluidic platform for a three-dimensional tissue model with a perfusable capillary network, which will allow, for the first time, a perfusion-culture in a tissue model with a high cell density. Our group previously reported that a spheroid of lung fibroblasts induced angiogenic sprouts from microchannels [1]. In this study, we successfully connected angiogenic sprouts to the vessel-like hollow structure in a spheroid and perfused the formed vascular network through microfluidic channels to the spheroid. This model opens up new techniques for tissue-culture for long-term.

Capillaries play a crucial role in the microcircu-latory system by exchanging metabolic substrates and waste products between blood and various tissues. The behavior of capillaries is affiliated with the number of capillaries per unit volume of tissue. Among the various noninvasive techniques available for analyzing skin microcirculation, nailfold capillaroscopy is considered to be a simple and easy-to-perform technique that allows a direct in-vivo visualization of the capillary network. Capillary density is one of the most important parameters in the studies involving capillaroscopy images. Capillary density in most of studies is defined as the number of capillaries in one millimeter span of the distal row in each finger or toe. This definition is silent about counting or excluding the number of capillary with different shapes. However, there is no single standard for counting the number of capillaries in a span of one millimeter. In this paper, a novel method is proposed for determining the nailfold capillary density. This method is a modified combination of two existing techniques: the direct observation and the 90° method. Compared to the two existing approaches, the proposed method is more straightforward and easy to use for cases in which the capillaries have different shapes and sizes. Through different examples, we have shown how this method can be used to select the apex point of capillary and subsequently count the number of capillaries with several papillae.

Recently, the study of in vitro capillary network using microfluidic devices by generating single concentration gradient have uncovered many biological information of angiogenesis. However, the platform for angiogenesis inhibitors have not been proposed. In this study, we have developed a microfluidic device for generation of multi gradients to stimuli cancer-induced angiogenesis and fibroblast-induced angiogenesis simultaneously. The device features an interaction chamber, connected to the surrounding channels with radian shaped low-height structures used to locate clusters of cells. The formation of multiple gradients is achieved in the interaction chamber through diffusion and sustained by continuous perfusion. Microfluidic valve was developed to control the direction of flow for trapping cells of different types respectively. We show that our device could generate multiple concentration gradient and trap clusters of cells. These results demonstrated that our device is able to stimuli the angiogenesis and can be used to do the angiogenesis inhibitor study.

As machine-to-machine applications using cellular systems become pervasive, it is an important concern that their deployment does not jeopardize the performance of the cellular systems. Support for a massive number of machines brings technical challenges affecting the performance of the random access channel and efficiency of radio resource allocation. Capillary networks are considered as an extensions to the cellular systems for providing large-scale connectivity. This paper proposes an aggregation scheme for capillary networks connected to the LTE network to improve their communication efficiency. A gateway, an intermediate unit between machines and the base station, aggregates packets from the machines during a predefined time, and then delivers them to the LTE network. In addition, this paper analyzes the trade-offs between random access interaction, resource allocation, and communication latency. Results reveals that accepting the extra latency for accumulating packets can significantly reduce the random access requests and the required resources for the data transmissions.

Due to diffusion limitation, tissues thicker than several hundred micrometers have difficulties in survival and proliferation. 3D bio-printing technology enables to create fluidic channels within tissue structures for appropriate media perfusion. This solution supports viability for the simple tissue model with limited number of cells and scaffold types; however, an additional capillary network is essential for more complex and denser tissues. In this study, we developed a 3D printing method to construct larger fluidic vascular channels in mm-scale and to create adjacent capillary network through a natural maturation process, thus providing a method to connect the capillary network to the large perfused vascular channels. Our bio-printing technology has a great potential in engineering vascularized thick tissues and vascular niches, as the vascular channels are simultaneously created while cells and matrices are printed around the channels in desired 3D patterns.

Interstitial fluid flow has been studied by many cancer researchers for investigation on the effect of interstitial flow on drug delivery. This paper formulates blood flow through a capillary network induced by a solid tumor and fluid flow in a tumor's surrounding tissue and investigates the effects of consideration a remodeled network and adaptability of capillary on interstitial flow. Numerical results show that the prediction of interstitial pressure for the remodeled network shows a higher value compared to the rigid one. Results from interstitial fluid and blood distribution in normal and cancerous tissues have beneficial information about the prediction of successive drug delivery.

The technique to construct the artificial organ made of cultured cells is required in many fields such as tissue engineering and drug development. However, the tissue-like construction more than 200 μm thick has central hypoxia and results in necrosis because of the limitation of diffusion of materials. Then, we will propose a method to form a tissue-like construction including vascular network in itself. Biocompatible artificial vessel was wrapped in cell-sheet cocultivated with HUVEC and NIH3T3. Culture medium perfused into the artificial vessel will be diffused into the whole construction through vascular network of HUVEC. This technique will be increases the viability of the cells in the construction.

The objectives of this research are to determine the temperature distribution due to micro-bubble oscillation in a microscopic brain capillary network under acoustic excavation. The Navier-Stokes equations and the modified Rayleigh-Plesset equations were combined to observe micro-bubble oscillation behavior. The Pennes bio-heat transfer equation (BHTE) was applied to model the heat transfer distribution based upon micro-bubble oscillation within both flexible and rigid vessel networks.

The aim of this paper is to present a two-dimensional simulation tool based on several mathematical models, visualizing the growth and development of a solid tumour in avascular growth phase, vascular growth phase and the progress of angiogenesis. The avascular tumour remains in a diffusion-limited state of a few millimeters in diameter, while during vascularized phase, tumour cell proliferating rapidly and being able to invade the surrounding host tissue and blood system. Tumour-induced angiogenesis, the growth of a capillary network of blood vessels from a pre-existing vasculature, provides the crucial link between the two stages. Under different molecular mechanisms, this discrete model demonstrates several important factors affecting tumour growth at each stage. The simulation results are presented in two-dimensional combined with quantitatively surveyed. The long-term goal of this work is to develop a multicellular engine for precisely simulating and visualizing the insight into cancer biology.

The delivery of a therapeutic agent through controlled carriers directly to the tumoral lesion can enhance treatment efficacy by reducing dosage while minimizing systemic circulation of toxic compounds through healthy tissues. As such, the induction of a feedback controlled steering force on ferromagnetic carriers from magnetic gradients generated by an upgraded clinical Magnetic Resonance Imaging (MRI) system has been demonstrated by our group. But the gradient strengths required in some sections of the capillary network may be technologically very difficult to achieve for human due mainly to the size and cooling issues of additional gradient coils embedded in the MRI bore. As such, the use of MC-1 Magnetotactic Bacteria (MTB) pushing microbeads with a therapeutic agent may provide complementary means of propulsion in smaller capillaries. Based on preliminary experimental results, carriers and a new method combining the induction of force in a ferromagnetic material with the thrust provided by MTB for direct targeting to the tumor mass are proposed. Keywords—Ferromagnetic, magnetotactic bacteria, MRI system, targeted drug delivery, angiogenesis capillary network.

Summary form only given. The treatment of cancer is one of the most challenging tasks of modern medicine and secondary toxicity remains a critical issue. Although intra-arterial chemotherapy or chemo-embolization provides interesting success, the release of drug in the systemic circulation prevents high intra-tumoral drug concentration to be sustained. Hence, targeting specifically the tumor cells becomes a major goal of modern oncology. As such, providing means of carrying microparticles for specific endovascular drug delivery or radioisotopes at the site of the tumor mass would be extremely attractive. Although we have shown experimentally that a clinical magnetic resonance imaging (MRI) system can propel a ferromagnetic core in a human cardiovascular network through an induced force generated by the same magnetic gradients used for MR-imaging, it becomes technological very challenging to apply this method to navigate particles in a 3D space in order to reach the tumor cells through an anarchic arteriolocapillar network stimulated by tumoral angiogenesis. Since the induction of a propulsion force decreases significantly for much smaller particles, propulsion in capillaries would require gradient amplitudes that are technologically and practically not an alternative considering the size and cooling issues of an additional gradient coils systems embedded in the MRI bore. Our proposed concept consists of using magnetotactic bacteria to push microbeads being coated with therapeutic agents in the capillary network. We have shown that the displacement path of a magnetotactic bacterium pushing a microbead can be modified by changing the orientation of the lines of a magnetic field. Preliminary experimental results also showed that magnetotactic bacteria of type MC-1 could swim efficiently in human blood and that a swarm of these bacteria could potentially be detected by MR-imaging. Although the DC magnetic field of clinical MRI systems complicates the directional control of such bacteria compared with an X-ray system that could be upgraded with peripheral permanent or electro-magnets, the use of an MRI system has many advantages in term of imaging modalities and the lack of radiation. We report preliminary studies related to local perturbations of the DC magnetic field of a clinical MRI system time multiplexed with imaging sequences that could allow the target delivery of therapeutic agents through microbeads being pushed by magnetotactic bacteria operating under computer control

We have previously developed general computational models for studying blood flow and oxygen transport in complex microvascular networks. Here we describe how these models can be used to study delivery of other chemical species such as therapeutic drugs. We first describe our model of microvascular blood flow and a three-dimensional, time-dependent transport model applicable when the species of interest is carried mainly in dissolved form in the blood and the systemic concentration is fixed. We then present results of numerical simulations of blood flow in a constructed three-dimensional capillary network. Finally, we perform simulations of mass transport in the network and present results indicating the spatial heterogeneity of the concentration in the tissue.

A previously described computational model (Ellis et al., 2002, and Goldman and Popel, 2000) for oxygen transport in capillary networks of the hamster cheek pouch retractor muscle is adapted to study the rat extensor digitorum longus muscle. Biophysical parameters from the literature are combined with experimental measurements to construct a model of capillary network structure and oxygen transport from blood to tissue. We describe how experimental values are related to model parameters, and how numerical simulations can be used to determine the effects of sepsis on oxygen transport heterogeneity and the development of localized tissue hypoxia.

A new computational method is developed for generating structurally realistic pulmonary capillary networks and for predicting pulmonary blood flow and RBC and neutrophil transit. Using this model, one can calculate local flow rate, pressure and hematocrit distributions in a capillary network, and evaluate the effects of transpulmonary pressure. Ptp, transcapillary pressure Ptm and capillary blockage on them. Comparisons with experimental data indicate that the predicted RBC transit time, the percentage of neutrophils passing through the network without stopping and their final aspect ratio agree well with measurements. This model also predicts the sample widely variable neutrophil transit times as are observed experimentally.