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ABSTRACT Objective Mathematical Framework Results Conclusion Neovascularization has been extensively studied because of its significant role in both physiological processes and diseases. The significance of vascular microfluidic platforms lies in its essential role in recreating an in vitro environment capable of supporting cellular and tissue systems through the process of neovascularization. Biomechanical properties in a tissue engineered system use fluid flow and transport properties to recapitulate physiological systems. This enables mimicry of organ systems which can further personalized and regenerative medicine. Thus, fluid hemodynamics can be used to study these flow patterns and create a system that mimics real physiological pathways and processes. The establishment of stable flow pathways encourages endothelial cells (ECs) ECs to undergo neovascularization. Specifically, the shear stress applied in capillary beds generates the increased proliferation and differentiation of ECs to build larger microcirculatory beds.Here, we describe a mathematical model that uses branching patterns and vessel morphology to predict hemodynamic parameters in capillary beds.A retinal capillary bed is used as one‐use case of our model to show how the mathematical framework can be used to determine hemodynamic parameters for any microfluidic system.In doing so, this tool can be altered to be used to supplement emerging research areas in neovascularization. [ABSTRACT FROM AUTHOR]

ObjectivesThe demand for energy in outdoor work and survival is increasing, and there are some significant shortcomings in the existing conventional energy supply methods, such as the need to carry a large amount of fuel for conventional generators and heavy weight of cells. Solar photovoltaic/thermal (PV/T) technology can effectively solve the problem of lack of energy for outdoor survival and field work. However, most of the existing PV/T collectors are rigid structures with large weight and are not easy to carry.MethodsA light and thin PV/T module based on the combination of a Cu(In,Ga)Se2(CIGS) thin film battery and a piece of capillary network were proposed. The energy collection performance of the module and the impact of water flow rate on the photoelectric and photothermal conversion efficiency of the module were studied experimentally.ResultsUnder the typical Shanghai climate conditions, the all-day electrical efficiency and thermal efficiency of the module are 13.04% and 22.50%, respectively. Under experimental conditions with an average irradiance of 760 ‍W/m², the optimal energy collection performance of this PV/T is achieved when the water flow rate is 2.1 ‍L/min. The cooling water in the capillary network can effectively reduce the cell temperature (by 10 ℃) and improve the energy utilization efficiency (by 23.94%).ConclusionsThe module has the characteristics of high power density, light weight and flexibility, and can be used for energy supply during outdoor work and survival, providing a new idea for the design of outdoor energy equipment.

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Melt electrowriting (MEW) is an electric-field-assisted additive biofabrication technique that has brought significant advancements to bioinspired scaffold design for soft tissue engineering and beyond. Owing to its targeted microfiber placement, MEW has become a powerful platform technology for the fabrication of in vitro disease models up to functional biohybrid constructs that are investigated in vivo to reach clinical translation soon. This work provides a concise overview of this rapidly evolving field by highlighting the key contributions of MEW to cardiovascular tissue engineering. Specifically, we i) pinpoint the methods to introduce microvascular networks in thick 3D constructs benefitting from (sacrificial) MEW microfibers, ii) report MEW-based concepts for small-diameter vascular grafts and stents, iii) showcase how contracting cardiac tissues can profit from the tunable structure–property relationship of MEW scaffolds, and iv) address how complete regenerative heart valves can be built on complex fiber scaffold architectures that recapitulate J-shaped tensile properties and tissue heterogeneity. Lastly, we touch on novel biomaterial advancements and discuss the technological challenges of MEW to unlock the full potential of this transformative technology.

Despite the significance of neck muscles in musculoskeletal disorders, their microscopic anatomy remains poorly characterized. This study examined the splenius capitis muscle, focusing on its fiber-type composition, fiber size, and capillary network characteristics. For comparison and validation, the vastus lateralis muscle was also analyzed. Muscle samples from 13 young male subjects (mean age ± SD: 35.7 ± 8.6 years) were collected within 24-h post-mortem during autopsy. Myosin heavy chain (MyHC) isoform expression was characterized immunohistochemically in 10 μm sections, while the capillary network architecture was assessed in 100 μm sections. Immunofluorescence staining, confocal microscopy, and 3D image analysis were employed to quantify capillary tortuosity, anisotropy, branch density (Br dens), and the length of capillaries per muscle volume (LV), per muscle fiber length (LL), per fiber surface area (LS), and per fiber volume (LVf). Compared to the vastus lateralis muscle, the splenius capitis muscle had a higher percentage of type 1 fibers (51.2% vs 39.7%), fewer type 2a fibers (16.2% vs 31.4%), and smaller fiber diameters (35.5–40.9 μm vs 47–56.1 μm). It also displayed lower Br dens (P = 0.0069), higher anisotropy (P = 0.0004), and lower LL (P < 0.0001) but higher LVf (P = 0.0486). In the splenius capitis muscle, body mass index (BMI) negatively correlated with LV (P = 0.0155), LS (P = 0.0091), LVf (P = 0.0137), and anisotropy (P = 0.0425), and positively correlated with tortuosity (P = 0.0473), indicating a reduction in the capillary network. In the vastus lateralis muscle, only LV (P = 0.0161) decreased with high BMI. This study characterized the fiber-type composition, fiber size, and 3D capillary network of the splenius capitis muscle, establishing a baseline for investigations into pathological muscle alterations.

Yanchun Hu,1 Anming Hu,2 Shenju Song3 1Department of Orthopaedics, the Fifth People’s Hospital of Jinan, Jinan, People’s Republic of China; 2Taishan College, Shandong University, Jinan, People’s Republic of China; 3Department of Nursing, the Fifth People’s Hospital of Jinan, Jinan, People’s Republic of ChinaCorrespondence: Yanchun Hu, Department of Orthopaedics, the Fifth People’s Hospital of Jinan, No. 24297 of Jingshi Road, Jinan, 250022, People’s Republic of China, Tel +86 531 87198016, Email huyanchun@21cn.comAbstract: High blood pressure (BP) is a common disease and is associated with many chronic diseases. Measuring BP is essential for the treatment and management of many diseases, and therefore there is a growing need for a non-invasive, sleeveless and continuous BP monitoring device. With the development of technology, pulse waveform analysis using photoplethysmography (PPG) has become more feasible for evaluating BP. This study aimed to evaluate the changes of vascular elasticity and blood volume over time by using the characteristic parameters extracted by PPG. We reviewed the latest progress and literature on the observation of capillary network characteristics in hypertensive and non-hypertensive patients by PPG, the influence of different drugs on microcirculation characteristics in hypertensive patients with PPG, and further explored the key relationship between microcirculation and hypertension. We found that the PPG waveform produced by the fingertips of hypertensive patients is very different from that of healthy people, and the PPG waveform changes significantly during diastolic period after antihypertensive treatment. With the rapid development of medical technology, people can get more intuitive microcirculation image data, which provides beneficial help for the comprehensive understanding of hypertension.Keywords: capillary network, microcirculation, hypertension, PPG, arteriovenous anastomosis

Idiopathic macular telangiectasia refers to a disease entity characterized by telangiectasia and alteration of the juxtafoveal capillary network. It can present uniocularly or binocularly and is subdivided into three groups which have varied appearances. Group I occurs in males which is easily identifiable and has macular edema. Group II has no sex predilection and difficult to distinguish by clinical examination and often requires the need of optical coherence tomography and angiographic modalities. Group III is not so common with its progressive nature and associated with neurological diseases. This article is aimed to provide complete details about idiopathic macular telangiectasia/idiopathic juxtafoveal telangiectasia/parafoveal telangiectasia including various groups, pathology, presentation, and management. [ABSTRACT FROM AUTHOR]

This study investigated the partitioning characteristics of red blood cells (RBCs) within capillaries, with a specific focus on ladder structures observed near the end of the capillaries. In vitro experiments were conducted using microfluidic channels with a ladder structure model comprising six bifurcating channels that exhibited an anti-parallel flow configuration. The effects of various factors, such as the parent channel width, distance between branches, and hematocrit, on RBC partitioning in bifurcating channels were evaluated. A decrease in the parent channel width resulted in an increase in the heterogeneity in the hematocrit distribution and a bias in the fractional RBC flux. Additionally, variations in the distance between branches affected the RBC distribution, with smaller distances resulting in greater heterogeneity. The bias of the RBC distribution in the microchannel cross section had a major effect on the RBC partitioning characteristics. The influence of hematocrit variations on the RBC distribution was also investigated, with lower hematocrit values leading to a more pronounced bias in the RBC distribution. Overall, this study provides valuable insights into RBC distribution characteristics in capillary networks, contributing to our understanding of the physiological mechanisms of RBC phase separation in the microcirculatory system. These findings have implications for predicting oxygen heterogeneity in tissues and could aid in the study of diseases associated with impaired microcirculation. [ABSTRACT FROM AUTHOR]

Idiopathic macular telangiectasia refers to a disease entity characterized by telangiectasia and alteration of the juxtafoveal capillary network. It can present uniocularly or binocularly and is subdivided into three groups which have varied appearances. Group I occurs in males which is easily identifiable and has macular edema. Group II has no sex predilection and difficult to distinguish by clinical examination and often requires the need of optical coherence tomography and angiographic modalities. Group III is not so common with its progressive nature and associated with neurological diseases. This article is aimed to provide complete details about idiopathic macular telangiectasia/idiopathic juxtafoveal telangiectasia/parafoveal telangiectasia including various groups, pathology, presentation, and management.

Gas discharge in heterogeneous porous dielectric (PD) is becoming a reliable and popular low-temperature plasma technique in surface modification and plasma catalysis. However, the exact breakdown characteristics in the PD are not well studied due to experimental and diagnostic limitations. In this paper, a fluid model is then used to simulate the gas breakdown characteristics in real PD. It is found that the breakdown will selectively occur in PDs. The spatial distribution of PD determines regions of local breakdown. Variations in pressure result in the rearrangement of breakdown probability in each region of PD so that breakdown regions will change. In order to explain the selective breakdown phenomenon, based on the assumption that a PD can be simplified into a network consisting of multiple tortuous capillaries, we developed a theoretical model of the breakdown in a capillary network. Three geometrical factors, i.e. capillary tortuosity, capillary radius, and line porosity, are taken into the model to account for the effect of electric field distortion and electron loss on the dielectric walls in the presence of PD. The calculated results explain the selective breakdown phenomenon occurring in the numerical simulation. This paper simulates the breakdown in a real PD and provides a quantitative theoretical model to analyze the geometrical effect of PD on the breakdown. This paper will also provide insights into the design of optimal parameters for porous dielectric discharge in surface modification and plasma catalysis. [ABSTRACT FROM AUTHOR]

Simple Summary: The crown pulp of permanent brachydont (short-crowned) teeth features a stratigraphic arrangement composed of a cell-free and a cell-rich zone. This stratigraphy is assumed to reflect a mature, less active status with only minor production of secondary dentin. In contrast, the hypsodont (high-crowned) equine tooth is required to sustain a production of large amounts of subocclusal dentin to compensate for lifelong occlusal wear of several mm per year. It is hypothesized that the remarkable productivity of the equine pulp is reflected by distinct histomorphological features of the pulpal tissue. Therefore, teeth of horses of different ages were investigated, paying special attention to identify the cellular arrangement at the pulp–dentin interface. In general, the layer of odontoblasts was followed by a dense arrangement of fibroblastic cells in a network of small-sized blood vessels as well as a high concentration of single nerve fibers, suggesting a subodontoblastic supportive zone. The formation of distinct zones as described in the brachydont crown pulp is absent. The observed histomorphological characteristics of the equine pulp are regarded as representing a highly productive status, which presumably accounts for the reception of mechanical stimuli; a high capacity for cellular regeneration; and finally, the required subocclusal dentin production. In the crown pulp of brachydont teeth, a cell-free and a cell-rich zone are established beneath the odontoblastic layer, indicating a mature status. For the equine dental pulp, there are no descriptions which allow for a comparative analysis with regard to functional requirements in terms of lifelong secondary dentin production to compensate for occlusal wear. For histomorphological and immunohistological investigations, ten incisors and ten check teeth were used from seven adult horses and five foals. In the periphery of the equine dental pulp, a constant predentin and odontoblastic cell layer was present, followed by densely packed fibroblastic cells, capillary networks, and a high concentration of nerve fibers, suggesting a subodontoblastic supportive zone. Whilst the size of the equine dental pulp decreased with age, the numbers of blood vessels, nerve fibers, and fibroblastic cells increased with age. Histological analysis of the equine dental pulp did not show a cell-free and cell-rich zone as described in the brachydont crown pulp. The equine dental pulp remained in a juvenile status even in aged horses, with morphological features indicating a high capacity for dentine production. [ABSTRACT FROM AUTHOR]

Melt electrowriting (MEW) is an electric-field-assisted additive biofabrication technique that has brought significant advancements to bioinspired scaffold design for soft tissue engineering and beyond. Owing to its targeted microfiber placement, MEW has become a powerful platform technology for the fabrication of in vitro disease models up to functional biohybrid constructs that are investigated in vivo to reach clinical translation soon. This work provides a concise overview of this rapidly evolving field by highlighting the key contributions of MEW to cardiovascular tissue engineering. Specifically, we i) pinpoint the methods to introduce microvascular networks in thick 3D constructs benefitting from (sacrificial) MEW microfibers, ii) report MEW-based concepts for small-diameter vascular grafts and stents, iii) showcase how contracting cardiac tissues can profit from the tunable structure-property relationship of MEW scaffolds, and iv) address how complete regenerative heart valves can be built on complex fiber scaffold architectures that recapitulate J-shaped tensile properties and tissue heterogeneity. Lastly, we touch on novel biomaterial advancements and discuss the technological challenges of MEW to unlock the full potential of this transformative technology., Competing Interests: ED-J-P is cofounder and director of CoraMetix Pty Ltd., which holds two patent applications related to 3D-printed heart valves. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission., (Copyright © 2024 Mueller, Mansi, De-Juan-Pardo and Mela.)

This study investigated the partitioning characteristics of red blood cells (RBCs) within capillaries, with a specific focus on ladder structures observed near the end of the capillaries. In vitro experiments were conducted using microfluidic channels with a ladder structure model comprising six bifurcating channels that exhibited an anti-parallel flow configuration. The effects of various factors, such as the parent channel width, distance between branches, and hematocrit, on RBC partitioning in bifurcating channels were evaluated. A decrease in the parent channel width resulted in an increase in the heterogeneity in the hematocrit distribution and a bias in the fractional RBC flux. Additionally, variations in the distance between branches affected the RBC distribution, with smaller distances resulting in greater heterogeneity. The bias of the RBC distribution in the microchannel cross section had a major effect on the RBC partitioning characteristics. The influence of hematocrit variations on the RBC distribution was also investigated, with lower hematocrit values leading to a more pronounced bias in the RBC distribution. Overall, this study provides valuable insights into RBC distribution characteristics in capillary networks, contributing to our understanding of the physiological mechanisms of RBC phase separation in the microcirculatory system. These findings have implications for predicting oxygen heterogeneity in tissues and could aid in the study of diseases associated with impaired microcirculation.

Remodeling of capillary rarefaction and deleterious arteries are characteristic hallmarks of hypertension that are partially corrected by exercise training. In addition, experimental evidence showed capillary rarefaction within the brain cortex and reduced cerebral blood flow. There is no information on hypertension- and exercise-induced effects on capillary profile and function within preautonomic nuclei. We sought now to evaluate the effects of hypertension and exercise training (T) on the capillary network within hypothalamic paraventricular (PVN) and solitary tract (NTS) nuclei, and on the remodeling of brain arteries. Age-matched spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY), submitted to moderate T or kept sedentary (S) for three months, were chronically cannulated for hemodynamic recordings at rest. Rats were anesthetized for i.v. administration of fluorescein isothiocyanate (FITC)-dextran (capillary volume/density measurements) or 4% paraformaldehyde perfusion (basilar, middle, and posterior arteries' morphometry) followed by brain harvesting and processing. Other groups of conscious rats had carotid blood flow (CBF, ultrasound flowmeter) acquired simultaneously with hemodynamic recordings at rest and exercise. SHR-S exhibited elevated pressure and heart rate, reduced CBF, increased wall/lumen ratio of arteries, but no capillary rarefaction within the PVN and NTS. T improved performance gain and caused resting bradycardia in both groups; reduction of pressure and sympathetic vasomotor activity and normalization of the wall/lumen ratio were only observed in SHR-T. T groups responded with marked PVN and NTS capillary angiogenesis and augmented CBF during exercise; to avoid overperfusion at rest, reduced basal CBF was observed only in WKY-T. Data indicated that the absence of SHR-S capillary rarefaction and the intense SHR-T angiogenesis within autonomic areas associated with correction of deleterious arteries' remodeling are essential adjustments to hypertension and exercise training, respectively. These adaptive responses maintain adequate baseline perfusion in SHR-S and SHR-T preautonomic nuclei, augmenting it in exercised rats when a well-coordinated autonomic control is required. [ABSTRACT FROM AUTHOR]

Remodeling of capillary rarefaction and deleterious arteries are characteristic hallmarks of hypertension that are partially corrected by exercise training. In addition, experimental evidence showed capillary rarefaction within the brain cortex and reduced cerebral blood flow. There is no information on hypertension- and exercise-induced effects on capillary profile and function within preautonomic nuclei. We sought now to evaluate the effects of hypertension and exercise training (T) on the capillary network within hypothalamic paraventricular (PVN) and solitary tract (NTS) nuclei, and on the remodeling of brain arteries. Age-matched spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY), submitted to moderate T or kept sedentary (S) for three months, were chronically cannulated for hemodynamic recordings at rest. Rats were anesthetized for i.v. administration of fluorescein isothiocyanate (FITC)-dextran (capillary volume/density measurements) or 4% paraformaldehyde perfusion (basilar, middle, and posterior arteries' morphometry) followed by brain harvesting and processing. Other groups of conscious rats had carotid blood flow (CBF, ultrasound flowmeter) acquired simultaneously with hemodynamic recordings at rest and exercise. SHR-S exhibited elevated pressure and heart rate, reduced CBF, increased wall/lumen ratio of arteries, but no capillary rarefaction within the PVN and NTS. T improved performance gain and caused resting bradycardia in both groups; reduction of pressure and sympathetic vasomotor activity and normalization of the wall/lumen ratio were only observed in SHR-T. T groups responded with marked PVN and NTS capillary angiogenesis and augmented CBF during exercise; to avoid overperfusion at rest, reduced basal CBF was observed only in WKY-T. Data indicated that the absence of SHR-S capillary rarefaction and the intense SHR-T angiogenesis within autonomic areas associated with correction of deleterious arteries' remodeling are essential adjustments to hypertension and exercise training, respectively. These adaptive responses maintain adequate baseline perfusion in SHR-S and SHR-T preautonomic nuclei, augmenting it in exercised rats when a well-coordinated autonomic control is required.

Accurate reproduction of human intestinal structure and function in vitro is of great significance for understanding the development and disease occurrence of the gut. However, most in vitro studies are often confined to 2D models, 2.5D organ chips or 3D organoids, which cannot fully recapitulate the tissue architecture, microenvironment and cell compartmentalization found in vivo . Herein, a centimeter-scale intestine tissue that contains intestinal features, such as hollow tubular structure, capillaries and tightly connected epithelium with in vivo-like ring folds, crypt-villi, and microvilli is constructed by 3D embedding bioprinting. In our strategy, a novel photocurable bioink composed of methacrylated gelatin, methacrylated sodium alginate and poly (ethylene glycol) diacrylate is developed for the fabrication of intestinal model. The Caco-2 cells implanted in the lumen are induced by the topological structures of the model to derive microvilli, crypt-villi, and tight junctions, simulating the intestinal epithelial barrier. The human umbilical vein endothelial cells encapsulated within the model gradually form microvessels, mimicking the dense capillary network in the intestine. This intestine-like tissue, which closely resembles the structure and cell arrangement of the human gut, can act as a platform to predict the therapeutic and toxic side effects of new drugs on the intestine., (© 2024 IOP Publishing Ltd.)

In the crown pulp of brachydont teeth, a cell-free and a cell-rich zone are established beneath the odontoblastic layer, indicating a mature status. For the equine dental pulp, there are no descriptions which allow for a comparative analysis with regard to functional requirements in terms of lifelong secondary dentin production to compensate for occlusal wear. For histomorphological and immunohistological investigations, ten incisors and ten check teeth were used from seven adult horses and five foals. In the periphery of the equine dental pulp, a constant predentin and odontoblastic cell layer was present, followed by densely packed fibroblastic cells, capillary networks, and a high concentration of nerve fibers, suggesting a subodontoblastic supportive zone. Whilst the size of the equine dental pulp decreased with age, the numbers of blood vessels, nerve fibers, and fibroblastic cells increased with age. Histological analysis of the equine dental pulp did not show a cell-free and cell-rich zone as described in the brachydont crown pulp. The equine dental pulp remained in a juvenile status even in aged horses, with morphological features indicating a high capacity for dentine production.

Objective(s): Multifunctional nanomedicine is the new generation of medicine, which is remarkably promising and associated with the minimum toxicity of targeted therapy. Distribution and transport of nanoparticles (NPs) in the blood flow are essential to the evaluation of delivery efficacy. Materials and Methods: In the present study, we initially designed a phantom based on Murray’s minimum work law using the AutoCAD software. Afterwards, the phantom was fabricated using lithography and imaged using a Siemens Magnetom 3T Prisma MRI scanner at the National Brain Mapping Laboratory, Iran. Finally, the velocity and pressure in the capillary network were simulated using the COMSOL software. Moreover, three-dimensional Navier-Stokes equations were applied to model the NP transport and dispersion in blood suspension. Results: According to the findings, particle size, vessel geometry, and vascular flow rate affected the delivery efficacy and NP distribution. Cerebral blood flow, cerebral blood volume, mean transit time, and curves for the capillary network were obtained at different times. The simulations indicated that the velocity and pressure in the capillary network were within the ranges of 0.0001-0.0005 m/s and 5-25 mm/Hg, respectively. Higher particle concentration was also observed in the non-uniform NP distribution profile near the vessel wall. Conclusion: We investigated the effects of the vessel size and geometry and particulate nature of blood on the delivery and distribution of NPs. For targeted drug delivery applications, a mechanistic understanding on the nanomedicine design was provided as well.

Biomarker development is a key clinical research need in sickle cell disease (SCD). Hemorheological parameters are excellent candidates as abnormal red blood cell (RBC) rheology plays a critical role in SCD pathophysiology. Here we describe a microfluidic device capable of evaluating RBC deformability and adhesiveness concurrently, by measuring their effect on perfusion of an artificial microvascular network (AMVN) that combines microchannels small enough to require RBC deformation, and laminin (LN) coating on channel walls to model intravascular adhesion. Each AMVN device consists of three identical capillary networks, which can be coated with LN (adhesive) or left uncoated (non-adhesive) independently. The perfusion rate for sickle RBCs in the LN-coated networks (0.18 ± 0.02 nL/s) was significantly slower than in non-adhesive networks (0.20 ± 0.02 nL/s), and both were significantly slower than the perfusion rate for normal RBCs in the LN-coated networks (0.22 ± 0.01 nL/s). Importantly, there was no overlap between the ranges of perfusion rates obtained for sickle and normal RBC samples in the LN-coated networks. Interestingly, treatment with poloxamer 188 decreased the perfusion rate for sickle RBCs in LN-coated networks in a dose-dependent manner, contrary to previous studies with conventional assays, but in agreement with the latest clinical trial which showed no clinical benefit. Overall, these findings suggest the potential utility of the adhesive AMVN device for evaluating the effect of novel curative and palliative therapies on the hemorheological status of SCD patients during clinical trials and in post-market clinical practice.

Biomarker development is a key clinical research need in sickle cell disease (SCD). Hemorheological parameters are excellent candidates as abnormal red blood cell (RBC) rheology plays a critical role in SCD pathophysiology. Here we describe a microfluidic device capable of evaluating RBC deformability and adhesiveness concurrently, by measuring their effect on perfusion of an artificial microvascular network (AMVN) that combines microchannels small enough to require RBC deformation, and laminin (LN) coating on channel walls to model intravascular adhesion. Each AMVN device consists of three identical capillary networks, which can be coated with LN (adhesive) or left uncoated (non-adhesive) independently. The perfusion rate for sickle RBCs in the LN-coated networks (0.18 ± 0.02 nL/s) was significantly slower than in non-adhesive networks (0.20 ± 0.02 nL/s), and both were significantly slower than the perfusion rate for normal RBCs in the LN-coated networks (0.22 ± 0.01 nL/s). Importantly, there was no overlap between the ranges of perfusion rates obtained for sickle and normal RBC samples in the LN-coated networks. Interestingly, treatment with poloxamer 188 decreased the perfusion rate for sickle RBCs in LN-coated networks in a dose-dependent manner, contrary to previous studies with conventional assays, but in agreement with the latest clinical trial which showed no clinical benefit. Overall, these findings suggest the potential utility of the adhesive AMVN device for evaluating the effect of novel curative and palliative therapies on the hemorheological status of SCD patients during clinical trials and in post-market clinical practice. [ABSTRACT FROM AUTHOR]

A functional vascular network is essential to the correct wound healing. In sprouting angiogenesis, vascular endothelial growth factor (VEGF) regulates the formation of new capillaries from pre-existing vessels. This is a very complex process and mathematical formulation permits to study angiogenesis using less time-consuming, reproducible and cheaper methodologies. This study aimed to mimic the chemoattractant effect of VEGF in stimulating sprouting angiogenesis. We developed a numerical model in which endothelial cells migrate according to a diffusion-reaction equation for VEGF. A chick chorioallantoic membrane (CAM) bioassay was used to obtain some important parameters to implement in the model and also to validate the numerical results. We verified that endothelial cells migrate following the highest VEGF concentration. We compared the parameters—total branching number, total vessel length and branching angle—that were obtained in the in silico and the in vivo methodologies and similar results were achieved (p-value smaller than 0.5; n = 6). For the difference between the total capillary volume fractions assessed using both methodologies values smaller than 15% were obtained. In this study we simulated, for the first time, the capillary network obtained during the CAM assay with a realistic morphology and structure. [ABSTRACT FROM AUTHOR]

Abstract Stem cell-based cardiac regenerative therapy is expected to be a promising strategy for the treatment of severe heart diseases. Pluripotent stem cells enabled us to reconstruct regenerated myocardium in injured hearts as an engineered tissue aiming for cardiac regeneration. To establish a long-term survival of transplanted three-dimensional (3D) engineered heart tissues in vivo, it is indispensable to induce microcapillaries into the engineered tissues after transplantation. Using temperature-responsive culture surface, we have developed pluripotent stem cell-derived cardiac tissue sheets including multiple cardiac cell lineages. The application of gelatin hydrogel microsphere between the cell sheet stacks enabled us to generate thick stacked cell sheets with functional vascular network in vivo. Another technology to generate 3D engineered cardiac tissues using cardiac cells and biomaterials also validated successful induction of vascular network originated from both host and graft-derived vascular cells.

Introduction: Resurfacing complex full thickness wounds requires free tissue transfer which creates donor site morbidity. We describe a method to fabricate a skin flap equivalent with a hierarchical microvascular network. Materials & methods: We fabricated a flap of skin-like tissue containing a hierarchical vascular network by sacrificing Pluronic® F127 macrofibers and interwoven microfibers within collagen encapsulating human pericytes and fibroblasts. Channels were seeded with smooth muscle and endothelial cells. Constructs were topically seeded with keratinocytes. Results: After 28 days in culture, multiphoton microscopy revealed a hierarchical interconnected network of macro- and micro-vessels; larger vessels (>100 μm) were lined with a monolayer endothelial neointima and a subendothelial smooth muscle neomedia. Neoangiogenic sprouts formed in the collagen protodermis and pericytes self-assembled around both fabricated vessels and neoangiogenic sprouts. Conclusion: We fabricated a prevascularized scaffold containing a hierarchical 3D network of interconnected macro- and microchannels within a collagen protodermis subjacent to an overlying protoepidermis with the potential for recipient microvascular anastomosis. [ABSTRACT FROM AUTHOR]

Information on the pattern of oxygen diffusion in skeletal muscles of bony fish is discussed. This diffusion is determined by a number of variables. Endothelium of microcirculatory vessels should not be considered the main barrier for oxygen diffusion, as it has large pores and perforations. The main diffusion barrier is cytoplasmic and intracellular membranes of muscle fibers. A substantial contribution to the concept of "facilitated diffusion" at the cellular level is made by the myoglobin and content of lipids, primarily triacylglycerides. Data on the structure and functional features of myoglobins of skeletal muscles and heart in bony fish are summarized. Information on the pattern of organization of the polypeptide chain of this protein, key substitutions, polymorphism, and kinetic characteristics of oxygen binding is provided. A comparison between species has revealed a relationship between the density of capillary network and the myoglobin and lipid content of muscles. The myoglobin and lipid content of fish muscle tissue is quite labile and depends on the condition of both the environment and the organism. This gives reason to consider the above parameters as factors that can perform a directed correction of the oxygen regime in fish muscle tissue, increasing its resistance to oxygen deficiency. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis initiated by cancerous cells is the process by which new blood vessels are formed to enhance oxygenation and growth of tumor. Objective: In this paper, we present a new multiscale mathematical model for the formation of a vascular network in tumor angiogenesis process. Methods: Our model couples an improved sprout spacing model as a stochastic mathematical model of sprouting along an existing parent blood vessel, with a mathematical model of sprout progression in the extracellular matrix (ECM) in response to some tumor angiogenic factors (TAFs). We perform simulations of the siting of capillary sprouts on an existing blood vessel using finite difference approximation of the dynamic equations of some angiogenesis activators and inhibitors. Angiogenesis activators are chemicals secreted by hypoxic tumor cells for initiating angiogenesis, and inhibitors of the angiogenesis are chemicals that are produced around every new sprout during tumor angiogenesis to inhibit the formation of further sprouts as a feedback of sprouting in angiogenesis. Moreover, for modelling sprout progression in ECM, we use three equations for the motility of endothelial cells at the tip of the activated sprouts, the consumption of TAF and the production and uptake of Fibronectin by endothelial cells. Results: Coupling these two basic models not only does provide a better time estimation of angiogenesis process, but also it is more compatible with reality. Conclusion: This model can be used to provide basic information for angiogenesis in the related studies. Related simulations can estimate the position and number of sprouts along parent blood vessel during the initial steps of angiogenesis and models the process of sprout progression in ECM until they vascularize a tumor.

The alveolar capillary network (ACN) has a large surface area that provides the basis for an optimized gas exchange in the lung. It needs to adapt to morphological changes during early lung development and alveolarization. Structural alterations of the pulmonary vasculature can lead to pathological functional conditions such as in bronchopulmonary dysplasia and various other lung diseases. To understand the development of the ACN and its impact on the pathogenesis of lung diseases, methods are needed that enable comparative analyses of the complex three-dimensional structure of the ACN at different developmental stages and under pathological conditions. In this study a newborn mouse lung was imaged with serial block-face scanning electron microscopy (SBF-SEM) to investigate the ACN and its surrounding structures before the alveolarization process begins. Most parts but not all of the examined ACN contain two layers of capillaries, which were repeatedly connected with each other. A path from an arteriole to a venule was extracted and straightened to allow cross-sectional visualization of the data along the path within a plane. This allows a qualitative characterization of the structures that erythrocytes pass on their way through the ACN. One way to define regions of the ACN supplied by specific arterioles is presented and used for analyses. Pillars, possibly intussusceptive, were found in the vasculature but no specific pattern was observed in regard to parts of the saccular septa. This study provides 3D information with a resolution of about 150 nm on the microscopic structure of a newborn mouse lung and outlines some of the potentials and challenges of SBF-SEM for 3D analyses of the ACN.

Despite the key role of the capillaries in neurovascular function, a thorough characterization of cerebral capillary network properties is currently lacking. Here, we define a range of metrics (geometrical, topological, flow, mass transfer, and robustness) for quantification of structural differences between brain areas, organs, species, or patient populations and, in parallel, digitally generate synthetic networks that replicate the key organizational features of anatomical networks (isotropy, connectedness, space-filling nature, convexity of tissue domains, characteristic size). To reach these objectives, we first construct a database of the defined metrics for healthy capillary networks obtained from imaging of mouse and human brains. Results show that anatomical networks are topologically equivalent between the two species and that geometrical metrics only differ in scaling. Based on these results, we then devise a method which employs constrained Voronoi diagrams to generate 3D model synthetic cerebral capillary networks that are locally randomized but homogeneous at the network-scale. With appropriate choice of scaling, these networks have equivalent properties to the anatomical data, demonstrated by comparison of the defined metrics. The ability to synthetically replicate cerebral capillary networks opens a broad range of applications, ranging from systematic computational studies of structure-function relationships in healthy capillary networks to detailed analysis of pathological structural degeneration, or even to the development of templates for fabrication of 3D biomimetic vascular networks embedded in tissue-engineered constructs.

Cortical microinfarcts are the most widespread form of brain infarction but frequently remain undetected by standard neuroimaging protocols. Moreover, microinfarcts are only partially detectable in hematoxylin-eosin-stained (H and E) 4-10 µm paraffin sections at routine neuropathological examination. In this short report, we provide two staining protocols for visualizing cortical microinfarcts in 100-300 µm sections. For low-power microscopy, the first protocol combines aldehyde fuchsine staining for detection of lipofuscin granules and macrophages with Darrow red counterstaining for Nissl material. The second protocol combines collagen IV immunohistochemistry with aldehyde fuchsine/Darrow red or with erythrosin-phosphotungstic acid-aniline blue staining for detailed study of the capillary network. In the first protocol, microinfarcts are recognizable as radially-oriented funnel-like accumulations of aldehyde fuchsine-positive macrophages. The second protocol recognizes microinfarcts and alterations of the capillary network, at whose center accumulations of dead neurons and aldehyde fuchsine-positive macrophages cluster. In addition, the second protocol permits visualization of abnormalities within the capillary network associated with more recent microinfarcts. Both protocols can be useful for comparing MRI datasets with cortical microinfarcts in corresponding whole brain sections of 100-300 µm thickness.

Characterization of the cardiac capillary network structure is of critical importance to understand the normal coronary functional properties and coronary microvascular diseases. The aim of our study was to establish an accessible methodology for 3D imaging and 3D processing to quantitatively characterize the capillary coronary network architecture in mice. Experiments were done on C57BL/6J mice. 3D imaging was performed by light sheet microscopy and confocal microscopy on iDISCO+ optical cleared hearts after labelling of the capillary endothelium by lectin injection. 3D images were processed with the open source software ImageJ. Non-visual image segmentation was based of the frequency distribution of the voxel greyscale values, followed by skeletonization and distance mapping. Capillary networks in left and right ventricles and septum were characterized by the volume network density, the fractal dimension, the number of segments and nodes and their ratio, the total network length, and the average length, diameter, and tortuosity of the segments. Scale-dependent parameter values can be impacted by the resolution limit of the 3D imaging technique. The proposed standardized methodology for 3D image processing is easily accessible for a biologist in terms of investment and difficulty level, and allows the quantification of the 3D capillary architecture and its statistical comparison in different conditions.

The alveolar capillary network (ACN) has a large surface area that provides the basis for an optimized gas exchange in the lung. It needs to adapt to morphological changes during early lung development and alveolarization. Structural alterations of the pulmonary vasculature can lead to pathological functional conditions such as in bronchopulmonary dysplasia and various other lung diseases. To understand the development of the ACN and its impact on the pathogenesis of lung diseases, methods are needed that enable comparative analyses of the complex three-dimensional structure of the ACN at different developmental stages and under pathological conditions. In this study a newborn mouse lung was imaged with serial block-face scanning electron microscopy (SBF-SEM) to investigate the ACN and its surrounding structures before the alveolarization process begins. Most parts but not all of the examined ACN contain two layers of capillaries, which were repeatedly connected with each other. A path from an arteriole to a venule was extracted and straightened to allow cross-sectional visualization of the data along the path within a plane. This allows a qualitative characterization of the structures that erythrocytes pass on their way through the ACN. One way to define regions of the ACN supplied by specific arterioles is presented and used for analyses. Pillars, possibly intussusceptive, were found in the vasculature but no specific pattern was observed in regard to parts of the saccular septa. This study provides 3D information with a resolution of about 150 nm on the microscopic structure of a newborn mouse lung and outlines some of the potentials and challenges of SBF-SEM for 3D analyses of the ACN. [ABSTRACT FROM AUTHOR]

In obesity, the skeletal muscle capillary network regresses and the insulin-mediated capillary recruitment is impaired. However, it has been shown that in the early stage of advanced obesity, an increased functional vascular response can partially compensate for other mechanisms of insulin resistance. The present study aimed to investigate the changes in the capillary network around individual muscle fibres during the early stage of obesity and insulin resistance in mice using 3D analysis. Capillaries and muscle fibres of the gluteus maximus muscles of seven high-fat-diet-induced obese and insulin-resistant mice and seven age-matched lean healthy mice were immunofluorescently labelled in thick transverse muscle sections. Stacks of images were acquired using confocal microscope. Capillary network characteristics were estimated by methods of quantitative image analysis. Muscle fibre typing was performed by histochemical analysis of myosin heavy chain isoforms on thin serial sections of skeletal muscle. Capillary length per muscle fibre length and capillary length per muscle fibre surface were increased by 27% and 23%, respectively, around small muscle fibres in obese mice, while there were no significant comparative differences around large fibres of obese and lean mice. Furthermore, the capillarization was larger around small compared to large fibres and there was a shift toward fast type myosin heavy chain isoforms, with no significant changes in muscle fibre diameters, tortuosity and anisotropy in obese mice. Overall, the results show that obese insulin-resistant mice have selective increase in capillarization around small predominantly intermediate muscle fibres, which is most likely related to the impaired glucose metabolism characteristic of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective(s): Multifunctional nanomedicine is the new generation of medicine, which is remarkably promising and associated with the minimum toxicity of targeted therapy. Distribution and transport of nanoparticles (NPs) in the blood flow are essential to the evaluation of delivery efficacy. Materials and Methods: In the present study, we initially designed a phantom based on Murray’s minimum work law using the AutoCAD software. Afterwards, the phantom was fabricated using lithography and imaged using a Siemens Magnetom 3T Prisma MRI scanner at the National Brain Mapping Laboratory, Iran. Finally, the velocity and pressure in the capillary network were simulated using the COMSOL software. Moreover, three-dimensional Navier-Stokes equations were applied to model the NP transport and dispersion in blood suspension. Results: According to the findings, particle size, vessel geometry, and vascular flow rate affected the delivery efficacy and NP distribution. Cerebral blood flow, cerebral blood volume, mean transit time, and curves for the capillary network were obtained at different times. The simulations indicated that the velocity and pressure in the capillary network were within the ranges of 0.0001-0.0005 m/s and 5-25 mm/Hg, respectively. Higher particle concentration was also observed in the non-uniform NP distribution profile near the vessel wall. Conclusion: We investigated the effects of the vessel size and geometry and particulate nature of blood on the delivery and distribution of NPs. For targeted drug delivery applications, a mechanistic understanding on the nanomedicine design was provided as well. [ABSTRACT FROM AUTHOR]

Despite the key role of the capillaries in neurovascular function, a thorough characterization of cerebral capillary network properties is currently lacking. Here, we define a range of metrics (geometrical, topological, flow, mass transfer, and robustness) for quantification of structural differences between brain areas, organs, species, or patient populations and, in parallel, digitally generate synthetic networks that replicate the key organizational features of anatomical networks (isotropy, connectedness, space-filling nature, convexity of tissue domains, characteristic size). To reach these objectives, we first construct a database of the defined metrics for healthy capillary networks obtained from imaging of mouse and human brains. Results show that anatomical networks are topologically equivalent between the two species and that geometrical metrics only differ in scaling. Based on these results, we then devise a method which employs constrained Voronoi diagrams to generate 3D model synthetic cerebral capillary networks that are locally randomized but homogeneous at the network-scale. With appropriate choice of scaling, these networks have equivalent properties to the anatomical data, demonstrated by comparison of the defined metrics. The ability to synthetically replicate cerebral capillary networks opens a broad range of applications, ranging from systematic computational studies of structure-function relationships in healthy capillary networks to detailed analysis of pathological structural degeneration, or even to the development of templates for fabrication of 3D biomimetic vascular networks embedded in tissue-engineered constructs. [ABSTRACT FROM AUTHOR]

Recent applications of decellularized tissue have included the use of hydrogels for injectable materials and three-dimensional (3D) bioprinting bioink for tissue regeneration. Microvascular formation is required for the delivery of oxygen and nutrients to support cell growth and regeneration in tissues and organs. The aim of the present study was to evaluate the formation of capillary networks in decellularized extracellular matrix (d-ECM) hydrogels. The d-ECM hydrogels were obtained from the small intestine submucosa (SIS) and the urinary bladder matrix (UBM) after decellularizing with sodium deoxycholate (SDC) and high hydrostatic pressure (HHP). The SDC d-ECM hydrogel gradually gelated, while the HHP d-ECM hydrogel immediately gelated. All d-ECM hydrogels had low matrix stiffness compared to that of the collagen hydrogel, according to a compression test. D-ECM hydrogels with various elastic moduli were obtained, irrespective of the decellularization method or tissue source. Microvascular-derived endothelial cells were seeded on d-ECM hydrogels. Few cells attached to the SDC d-ECM hydrogel with no network formation, while on the HHP d-ECM hydrogel, a capillary network structure formed between elongated cells. Long, branched networks formed on d-ECM hydrogels with lower matrix stiffness. This suggests that the capillary network structure that forms on d-ECM hydrogels is closely related to the matrix stiffness of the hydrogel.

Background. One of the causes of eye diseases is the damage of the vascular bed components of the eyeball. Objective. To investigate peculiarities of the rat retinal blood supply from retinal pool. Methods. Adult male rats aged from 4,5–7,5 month were used. To investigate the blood supply of their retina, eye vessels were injected with contrast mass. Results. Vascularization of rat retina on micro-level is realized by the branches of central retinal artery that runs deep in the optic nerve and reaching its disk ramifies providing its vascularization. The main branches that ramify from the central retinal artery run from the area of optic disk to the periphery reaching deep into the layer of nerve fibers. These vessels include numerous arterioles and venules of the retina: dorsolateral, ventrolateral, dorsomedial, ventromedial, ventral and dorsal arterioles and venules of the macula. Each branch of the central retinal artery is divided dichotomously forming arterioles (of the first, second and third order). Near the optic nerve the diameter of arterioles of the first order is 80-100 microns. Subsequently these arterioles are dichotomously divided into second order arterioles with the diameter of 40-50 microns. And the second-order arterioles bifurcate into the third-order arterioles with the diameter of 10-20 microns. Arterioles further bifurcate and enter capillaries with the diameter ranging from 4.0 to 9.0 microns. The dense capillary network was traced over the entire area of the retina. In the deep retinal layers two capillary networks (superficial and deep) were visualized. Superficial capillary network was localized in the deep layer of nerve fibers and is clearly seen in all quadrants of the retina. Deep capillary network lies between the outer plexiform zone and the inner nuclear layer. These two capillary networks are interconnected with the help of anastomoses thus forming a morphological basis for compensatory mechanisms. There are non-vascular areas around the retinal artery located symmetrically on both sides of arteriole. The closer arterioles come to the periphery the more clearly we can see gradual disappearance of the deep capillary network and clear visualization of the surface capillary network dominates with capillaries having a wide diameter. The surface layer capillaries of rat’s retina are running radially from the optic nerve toward the edge of the posterior pole of the retina. Peripapillary capillaries are located at a considerable distance, and are rarely anastomosed to each other. Gradually passing into deeper layers of the retina peripapillary capillaries pass into venules. In the area of optic disk the retina contains another capillary network located in the outermost layer of nerve fibers. Capillaries in this region are located in the radial direction. We also found a capillary network in the normal rat’s retina in the area of macula. Loops of capillaries are polymorphous; they are twice longer than wide and run the same direction as branching arterioles. Retinal peripapillary capillary network is characterized by forward direction of capillaries, they have considerable length, with rarely encountered anastomosis and being located deep in the surface layers of nerve fibers of the retina. Conclusion. It was revealed that there are two capillary networks among rat’s retinal layers. Superficial capillary network is localized deep in the layer of nerve fibers and it is clearly seen in all quadrants of the retinal field. Deep capillary network lies between the outer plexiform zone and the inner nuclear layer. Additionaly capillary network was found in the region of optic disk which is located in the outermost layer of nerve fibers. Citation: Paltov EV. [Peculiarities of normal retinal blood supply from the side of retinal pool]. Morphologia. 2015;9(2):54-7. Ukrainian.

Highlights • Bio-inspired "fluidic diode" for unidirectional water transport (transport velocity ≈ 1 mm/s). • Unidirectional water transport even against gravity. • Large-area, passive, based on disposable polymer, i.e. laser-engraved in poly(methyl methacrylate) (PMMA). • Possible applications: biomedical microfluidics, lab-on-a-chip, micro-analysis devices, lubrication, cooling etc. Abstract In this paper, we describe the design, fabrication and functional principle of microfluidic diodes – devices for directional liquid transport. They are passive (i.e., need no external energy input) and are capable of unidirectional water transport even vertically against gravity, i.e. they prevent backflow of liquid. In designing the devices with an area of several cm2, we used a capillary channel network that was bio-inspired by the skin of the Texas horned lizard (Phrynosoma cornutum). By means of a CO 2 laser, we engraved the microfluidic structures into plates made of poly(methyl methacrylate) (PMMA), a low-cost technical polymer commonly used in disposable microfluidics. We then characterized the topography of the fabricated 3D structures by optical coherence tomography (OCT). Theoretical analysis of the OCT data enabled us to determine their working principle which differs from that presented previously in the literature. We accessed the fluid transport properties of the device by measuring distance, velocity, wetted area and flow asymmetry. Biomimetic abstraction led to a simplified structure which was validated experimentally. All tested devices allowed unidirectional liquid transport at velocities in the range of a few mm/s in the forward direction while preventing backflow of volumes of about 0.5 ml in the backward direction on an area of approximately 28 mm x 14 mm. The transport velocity of about 1 mm/s was found to be nearly constant for a distance of approximately 2 cm, beyond which it decreased. The application spectrum ranges from biomedical microfluidics, lab-on-a-chip and micro-analysis devices to filtration, lubrication, cooling of electronics and e-ink displays. [ABSTRACT FROM AUTHOR]

We develop the p-adic model of propagation of fluids (e.g., oil or water) in capillary networks in a porous random medium. The hierarchic structure of a system of capillaries is mathematically modeled by endowing trees of capillaries with the structure of an ultrametric space. Considerations are restricted to the case of idealized networks represented by homogeneous p-trees with p branches leaving each vertex, where p >1 is a prime number. Such trees are realized as the fields of p-adic numbers. We introduce and study an inhomogeneous Markov process describing the penetration of fluid into a porous random medium. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (DM2) is frequently accompanied by microcirculation complications, including structural and functional alterations, which may have serious effects on substance exchanges between blood and interstitial tissue and the health of organs. In this paper, we aim to study the influence of microcirculation alterations in DM2 patients on fluid and oxygen exchanges through a model analysis. A fluid flow and oxygen transport model were developed by considering the interplay between blood in capillary network and interstitial tissue. The two regions were separately represented by 1D network model and 3D volume model, and the immersed boundary method (IBM) was adopted to solve fluid and mass transfer between these two regions. By using the model, the steady flow field and the distributions of oxygen in capillary network and surrounding tissue were firstly simulated. In the interstitial volume, fluid pressure and oxygen tension decreased with the increase of distance from the network; in the network, oxygen tension in blood plasma dropped from 100 mm Hg at the entrance to about 40 mm Hg at the exit. We further tested several structural and functional disorders related to diabetic pathological conditions. Simulated results show that the impaired connectivity of the network could result in poor robustness in maintaining blood flow and perfused surface; under high fluid permeability conditions of capillary walls, the pressure gradient was much larger around the capillary bed, and this alteration led to a saturation level of the interstitial pressure when lymphatic flow drainage can't work effectively; the variations in network connectivity and permeability of capillary wall also had unfavorable influence on oxygen distributions in interstitial tissue. In addition, when the oxygen releasing capacity of hemoglobin was confined by glycosylated hemoglobin (HbA1) in the case of diabetes, the plasma could not be complemented with adequate oxygen and thus the hypoxic tissue range will be extended. This study illustrates that when microcirculation disturbances, including the structure of capillary network, the wall osmosis property and the capacity of blood binding oxygen occur in DM2, some negative impacts are raised on microvascular hemodynamics and metabolism circumstance of interstitial tissue. [ABSTRACT FROM AUTHOR]