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Purpose: The choice of surgical method for rhegmatogenous retinal detachment (RRD) may have a significant impact on the retina. In this study, we aimed to compare retinal function and structure after scleral buckling (SB) and phacovitrectomy (phaco-PPV) for macula-on RRD. Patients and Methods: This cross-sectional study included patients who underwent anatomically successful repair of macula-on RRD managed with SB (n=35) and phaco-PPV (n=35) between 2019– 2023. All participants were examined within 6– 20 months of surgery to evaluate the retinal structure using spectral domain optical coherence tomography (SD-OCT) and vessel density (VD) by OCT angiography (OCTA). Best-corrected visual acuity (BCVA) and microperimetry (MP) tests were used to assess the retinal function. Results: Analysis of the microvascular network with OCTA between eyes after surgery and healthy eyes showed a decrease in VD. Significant changes in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) were observed only in eyes after SB surgery (p < 0.001 and p=0.02, respectively). Analysis of retinal function assessed by MP showed a significant decrease (p< 0.05) in retinal sensitivity after phaco-PPV (24.81± 2.25 dB) and SB (24.18± 2.14 dB) operations compared to the healthy control group (25.97 ± 1.51 dB), whereas postoperative BCVA showed no differences (p> 0.05). Conclusion: Changes in retinal sensitivity were accompanied by impairment of the microvascular network in the eyes after SB and phaco-PPV surgeries due to macula-on RRD. Disorders were more pronounced in eyes following SB surgery, possibly secondary to mechanical stress. [ABSTRACT FROM AUTHOR]

In the tumor microenvironment (TME), the interaction between cancer cells and the microvascular network plays a crucial role in cancer progression. It is also well known that an extremely low oxygen concentration is generated in the TME. However, the effects of oxygen concentration on the interaction between cancer cells and the microvascular network remain poorly understood. In the present study, we developed a microfluidic device with three gel channels and used this device to co-culture cancer cells and a microvascular network. We then investigated the cellular dynamics at different oxygen concentrations. Cancer cells and cells forming a microvascular network (endothelial cells and fibroblasts) were separately mixed with fibrin gels and placed in separate gel channels that flanked a middle gel channel lacking cells. During a seven-day co-culture, the dynamics of cancer cells and formation of a three-dimensional microvascular structure were observed. Cell culture was conducted at three different oxygen concentrations: atmospheric oxygen (21% O2), physiological normoxia (5% O2), and physiological hypoxia (1% O2, resembling the TME). Inspection revealed that cancer cells migrated toward the microvascular network under the co-culture conditions, a property that was potentiated at lower oxygen levels. Under physiological normoxia, endothelial cells formed a thick, dense microvascular network rather than migrating towards the cancer cells. In contrast, under physiological hypoxia, endothelial cells did not exhibit angiogenesis toward cancer cells. These results suggest that the microfluidic device described here will be useful for investigating the interactions between cancer cells and microvascular network under various oxygen conditions. [ABSTRACT FROM AUTHOR]

Optical coherence tomography angiography (OCTA), a functional extension of optical coherence tomography (OCT), is widely employed for high‐resolution imaging of microvascular networks. However, due to the relatively low scan rate of OCT, the artifacts caused by the involuntary bulk motion of tissues severely impact the visualization of microvascular networks. This study proposes a fast motion correction method based on image feature matching for OCT microvascular images. First, the rigid motion‐related mismatch between B‐scans is compensated through the image feature matching based on the improved oriented FAST and rotated BRIEF algorithm. Then, the axial motion within A‐scan lines in each B‐scan image is corrected according to the displacement deviation between the detected boundaries achieved by the Scharr operator in a non‐rigid transformation manner. Finally, an optimized intensity‐based Doppler variance algorithm is developed to enhance the robustness of the OCTA imaging. The experimental results demonstrate the effectiveness of the method. [ABSTRACT FROM AUTHOR]

The microvascular network plays an important role in providing nutrients to the injured tissue and exchanging various metabolites. However, how to achieve efficient penetration of the injured tissue is an important bottleneck restricting the reconstruction of microvascular network. Herein, the hydrogel precursor solution can efficiently penetrate the damaged tissue area, and ultrasound triggers the release of thrombin from liposomes in the solution to hydrolyze fibrinogen, forming a fibrin solid hydrogel network in situ with calcium ions and transglutaminase as catalysts, effectively solving the penetration impedance bottleneck of damaged tissues and ultimately significantly promoting the formation of microvascular networks within tissues. First, the fibrinogen complex solution is effectively permeated into the injured tissue. Second, ultrasound triggered the release of calcium ions and thrombin, activates transglutaminase, and hydrolyzes fibrinogen. Third, fibrin monomers are catalyzed to form fibrin hydrogels in situ in the damaged tissue area. In vitro studies have shown that the fibrinogen complex solution effectively penetrated the artificial bone tissue within 15 s after ultrasonic triggering, and formed a hydrogel after continuous triggering for 30 s. Overall, this innovative strategy effectively solved the problem of penetration resistance of ultrasound‐triggered hydrogels in the injured tissues, and finally activates in situ microvascular networks regeneration. [ABSTRACT FROM AUTHOR]

Purpose: Mandibular reconstruction remains a challenging procedure despite the availability of various flaps and grafts. The ultimate objective is to restore oral functioning and attain acceptable morphological outcomes while considering donor site morbidity. This study describes the vascular supply and harvesting technique of a pedicled clavicular bone. The proximity of the clavicle is conducive to a mandibular replacement and allows the use of vascularized bone with a single surgical field. Methods: The osteoperiosteal clavicular pedicled flap was harvested on the right side of ten fresh cadaver specimens. The cervical transverse artery was injected with colored latex in some cases and methylene blue in others. Results: The vascular periosteal supply of the clavicular flap was highlighted. The clavicular bone was linked to its pedicle which was composed of vascular and adipose-fascial tissues, without any overlying skin paddle. Its vasculature was supplied by a reverse flow from the ascending cervical artery. The pedicled clavicular bone readily reached the mandible in all dissections. Conclusion: The osteoperiosteal vasculature of the clavicular flap is based on the transverse cervical artery which receives a reverse blood supply from the ascending cervical artery. This vascular pattern is reliable because of the existence of the sub-occipital microvascular network named the "Bosniak node." This pedicled clavicular flap seems to be a robust perspective in both mandibular and facial bone reconstruction. We do not claim that it will replace the existing approaches, but it will expand the surgical panel of mandibular reconstruction. Its clinical realisation will judge its functionality. [ABSTRACT FROM AUTHOR]

Abstract Tissue engineering and regenerative medicine have made great progress in recent decades, as the fields of bioengineering, materials science, and stem cell biology have converged, allowing tissue engineers to replicate the structure and function of various levels of the vascular tree. Nonetheless, the lack of a fully functional vascular system to efficiently supply oxygen and nutrients has hindered the clinical application of bioengineered tissues for transplantation. To investigate vascular biology, drug transport, disease progression, and vascularization of engineered tissues for regenerative medicine, we have analyzed different approaches for designing microvascular networks to create models. This review discusses recent advances in the field of microvascular tissue engineering, explores potential future challenges, and offers methodological recommendations.

Tissue engineering and regenerative medicine have made great progress in recent decades, as the fields of bioengineering, materials science, and stem cell biology have converged, allowing tissue engineers to replicate the structure and function of various levels of the vascular tree. Nonetheless, the lack of a fully functional vascular system to efficiently supply oxygen and nutrients has hindered the clinical application of bioengineered tissues for transplantation. To investigate vascular biology, drug transport, disease progression, and vascularization of engineered tissues for regenerative medicine, we have analyzed different approaches for designing microvascular networks to create models. This review discusses recent advances in the field of microvascular tissue engineering, explores potential future challenges, and offers methodological recommendations. [ABSTRACT FROM AUTHOR]

Objective: Fluid shear stress is thought to be a regulator of endothelial cell behavior during angiogenesis. The link, however, requires an understanding of stress values at the capillary level in angiogenic microvascular networks. Critical questions remain. What are the stresses? Do capillaries experience similar stress magnitudes? Can variations explain vessel‐specific behavior? The objective of this study was to estimate segment‐specific shear stresses in angiogenic networks. Methods: Images of angiogenic networks characterized by increased vascular density were obtained from rat mesenteric tissues stimulated by compound 48/80‐induced mast cell degranulation. Vessels were identified by perfusion of a 40 kDa fixable dextran prior to harvesting and immunolabeling for PECAM. Using a network flow‐based segment model with physiologically relevant parameters, stresses were computed per vessel for regions across multiple networks. Results: Stresses ranged from 0.003 to 2328.1 dyne/cm2 and varied dramatically at the capillary level. For all regions, the maximum segmental shear stresses were for capillary segments. Stresses along proximal capillaries branching from arteriole inlets were increased compared to stresses along capillaries in more distal regions. Conclusions: The results highlight the variability of shear stresses along angiogenic capillaries and motivate new discussions on how endothelial cells may respond in vivo to segment‐specific microenvironment during angiogenesis. [ABSTRACT FROM AUTHOR]

Highlights: This research presents the development of a hydrogel scaffold for an in vitro microvascultature. Here, the optimal hydrogel composition in terms of polymer type, ratio, and solvent is investigated. Scaffold optimisation for endothelial cells is based on a multipronged evaluation encompassing seeding number, cell adhesion, migration rate, cell viability, hydrogel consistency, and endothelial tube formation. The developed hydrogel constructs enabled the formation of interconnected capillary-like networks, which are also characterised to gain further insights into their microarchitecture. Traumatic injuries are a major cause of morbidity and mortality worldwide; however, there is limited research on microvascular traumatic injuries. To address this gap, this research aims to develop and optimise an in vitro construct for traumatic injury research at the microvascular level. Tissue engineering constructs were created using a range of polymers (collagen, fibrin, and gelatine), solvents (PBS, serum-free endothelial media, and MES/NaCl buffer), and concentrations (1–5% w/v). Constructs created from these hydrogels and HUVECs were evaluated to identify the optimal composition in terms of cell proliferation, adhesion, migration rate, viability, hydrogel consistency and shape retention, and tube formation. Gelatine hydrogels were associated with a lower cell adhesion, whereas fibrin and collagen ones displayed similar or better results than the control, and collagen hydrogels exhibited poor shape retention; fibrin scaffolds, particularly at high concentrations, displayed good hydrogel consistency. Based on the multipronged evaluation, fibrin hydrogels in serum-free media at 3 and 5% w/v were selected for further experimental work and enabled the formation of interconnected capillary-like networks. The networks formed in both hydrogels displayed a similar architecture in terms of the number of segments (10.3 ± 3.21 vs. 9.6 ± 3.51) and diameter (8.6446 ± 3.0792 μ m vs. 7.8599 ± 2.3794 μ m). [ABSTRACT FROM AUTHOR]

Anti-angiogenesis as a treatment strategy for normalizing the microvascular network of tumors is of great interest among researchers, especially in combination with chemotherapy or radiotherapy. According to the vital role that angiogenesis plays in tumor growth and in exposing the tumor to therapeutic agents, this work develops a mathematical framework to study the influence of angiostatin, a plasminogen fragment that shows the anti-angiogenic function, in the evolutionary behavior of tumor-induced angiogenesis. Angiostatin-induced microvascular network reformation is investigated in a two-dimensional space by considering two parent vessels around a circular tumor by a modified discrete angiogenesis model in different tumor sizes. The effects of imposing modifications on the existing model, i.e., the matrix-degrading enzyme effect, proliferation and death of endothelial cells, matrix density function, and a more realistic chemotactic function, are investigated in this study. Results show a decrease in microvascular density in response to the angiostatin. A functional relationship exists between angiostatin's ability to normalize the capillary network and tumor size or progression stage, such that capillary density decreases by 55%, 41%, 24%, and 13% in tumors with a non-dimensional radius of 0.4, 0.3, 0.2, and 0.1, respectively, after angiostatin administration.

Biomimetic microvascular networks prepared by coaxial electrospinning technology have attracted much attention as a novel form of carrier for encapsulating active substances. However, the poor interfacial bonding strength between traditional electrospinning materials and metal substrates limits its application in anti-corrosion coatings. Herein, a novel poly(vinyl alcohol) grafted phytic acid (PVA-PA) electrospinning solution was synthesized. And a sandwich-like microvascular network (SMN) was prepared by coaxial electrospinning technology, which used PVA-PA solution as the shell material, epoxy resin 51 (E51), tetraphenylethylene (TPE) and polyamide resin as the core materials, respectively. Owing to the high porosity of SMN, epoxy resin can be directly spin-coated on it to form a composite coating (PVA-PA/SMN/EP). It is proved that due to the strong chelation and coordination interaction between PA and mild steel, the pull-out adhesion of the PVA-PA/SMN/EP composite coatings on mild steel was increased by 0.92 MPa. In addition, by systematically optimizing the relative viscosity, miscibility, conductivity, and saturated vapor pressure between the two jets of the core solution and the shell solution in coaxial electrospinning, the microvascular structure of the coaxial electrospinning nanofibers was improved and the fluidity of the internal active substances was maintained. When the PVA-PA/SMN/EP composite coating generates microcracks, the active substances encapsulated in the SMN flow out, in which the three-dimensional crosslinked network formed by the curing of E51 and polyamide resin enhances the spatial interactions between TPE molecules, which results in TPE emitting a bright blue fluorescence. This work provides a new approach for the development of the next generation of smart anti-corrosion coatings. [Display omitted] • A smart coating integrating self-healing and self-reporting abilities is developed. • Novel waterborne poly(vinyl alcohol) grafted phytic acid electrospinning solution. • Enhanced interfacial bonding strength between poly(vinyl alcohol) fibers and metals • The microvascular structure of coaxial electrospinning nanofibers is optimized. • Fast and contactless optical observation of micro damages on coating is achieved. [ABSTRACT FROM AUTHOR]

Introduction: Visualization of the intact microvascular network in skeletal muscle requires labeling the entire network in whole mount preparations where muscle fibre length can be set to near optimal but the tools to do this are not clear., Methods: We intravascularly injected CD-1 mice with different fluorescently labelled lectins (fluorescent isolectin GS-IB4 [ISO], wheat germ agglutinin [WGA], lycopersicon esculentum [LYCO]) or FITC-labelled gel. Soleus, extensor digitorum longus, diaphragm, gluteus maximus and cremaster muscles were excised, pinned at optimal sarcomere length and viewed using fluorescence microscopy., Results: WGA and LYCO were effective at labeling the entire vascular network with WGA labeling capillaries more brightly. ISO labelled the arteriolar vasculature and early segments of the capillaries but not the full length of the capillaries or the venular network. FITC-labelled gel was effective at labelling the microvascular network but not all small vessels were consistently labelled. The pattern of staining for each labelling method was similar across all muscle fibre-types tested., Conclusions: WGA was optimal for perfusion labeling and visualization of the intact microvascular network in whole mount skeletal muscle preparations and can be used in combination with ISO to distinguish the arteriolar and venous sides of the network., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Abstract Background We present computational modeling of positron emission tomography radiotracer uptake with consideration of blood flow and interstitial fluid flow, performing spatiotemporally-coupled modeling of uptake and integrating the microvasculature. In our mathematical modeling, the uptake of fluorodeoxyglucose F-18 (FDG) was simulated based on the Convection–Diffusion–Reaction equation given its high accuracy and reliability in modeling of transport phenomena. In the proposed model, blood flow and interstitial flow are solved simultaneously to calculate interstitial pressure and velocity distribution inside cancer and normal tissues. As a result, the spatiotemporal distribution of the FDG tracer is calculated based on velocity and pressure distributions in both kinds of tissues. Results Interstitial pressure has maximum value in the tumor region compared to surrounding tissue. In addition, interstitial fluid velocity is extremely low in the entire computational domain indicating that convection can be neglected without effecting results noticeably. Furthermore, our results illustrate that the total concentration of FDG in the tumor region is an order of magnitude larger than in surrounding normal tissue, due to lack of functional lymphatic drainage system and also highly-permeable microvessels in tumors. The magnitude of the free tracer and metabolized (phosphorylated) radiotracer concentrations followed very different trends over the entire time period, regardless of tissue type (tumor vs. normal). Conclusion Our spatiotemporally-coupled modeling provides helpful tools towards improved understanding and quantification of in vivo preclinical and clinical studies.

The organ-specific metastatization of breast cancer to bone is driven by specific interactions between the host microenvironment and cancer cells (CCs). However, it is still unclear the role that circulating immune cells, including neutrophils, play during bone colonization (i.e. pro-tumoral vs. anti-tumoral). Here, we aimed at analyzing the migratory behavior of neutrophils when exposed to breast CCs colonizing the bone and their contribution to the growth of breast cancer micrometastases. Based on our previous bone metastasis models, we designed a microfluidic system that allows to independently introduce human vascularized breast cancer metastatic seeds within a bone-mimicking microenvironment containing osteo-differentiated mesenchymal stromal cells and endothelial cells (ECs). ECs self-assembled into microvascular networks and connected the bone-mimicking microenvironment with the metastatic seed. Compared to controls without CCs, metastatic seeds compromised the architecture of microvascular networks resulting in a lower number of junctions (5.7 ​± ​1.2 vs. 18.8 ​± ​4.5, p ​= ​0.025) and shorter network length (10.5 ​± ​1.0 vs. 13.4 ​± ​0.8 [mm], p ​= ​0.042). Further, vascular permeability was significantly higher with CCs (2.60 ​× ​10−8 ​± ​3.59 ​× ​10−8 ​vs. 0.53 ​× ​10−8 ​± ​0.44 ​× ​10−8 [cm/s], p ​= ​0.05). Following metastatic seed maturation, neutrophils were injected into microvascular networks resulting in a higher extravasation rate when CCs were present (27.9 ​± ​13.7 vs. 14.7 ​± ​12.4 [%], p ​= ​0.01). Strikingly, the percentage of dying CCs increased in presence of neutrophils, as confirmed by confocal imaging and flow cytometry on isolated cells from the metastatic seeds. The biofabricated metastatic niche represents a powerful tool to analyze the mechanisms of interaction between circulating immune cells and organ-specific micrometastases and to test novel drug combinations targeting the metastatic microenvironment.

Optical coherence tomography angiography (OCTA) can map microvascular networks and quantify blood flow velocities with high resolution by calculating intensity standard deviations of time‐series signals. However, statistical calculations of the standard deviations need much processing time and reduce the analysis efficiency. In this study, we proposed three optimized OCTA algorithms incorporating rapid estimations of the intensity standard deviations, including the range algorithm, the mean absolute error algorithm and the maximum absolute error algorithm. The abilities of the optimized algorithms to quantify the flow velocities were validated by a flow phantom. After a rat cerebral cortex was imaged, the optimized OCTA algorithms were compared with the conventional relative standard deviation algorithm in the metrics of imaging quality and processing time. The results show that the optimized algorithms incorporating rapid estimations of the intensity standard deviations have faster processing speeds with equivalent image quality. [ABSTRACT FROM AUTHOR]

We present a deep learning and simulation-based method to measure cortical capillary red blood cell (RBC) flux using Optical Coherence Tomography (OCT). This method is more accurate than the traditional peak-counting method and avoids any user parametrization, such as a threshold choice. We used data that was simultaneously acquired using OCT and two-photon microscopy to uncover the distribution of parameters governing the height, width, and inter-peak time of peaks in OCT intensity associated with the passage of RBCs. This allowed us to simulate thousands of time-series examples for different flux values and signal-to-noise ratios, which we then used to train a 1D convolutional neural network (CNN). The trained CNN enabled robust measurement of RBC flux across the entire network of hundreds of capillaries. [ABSTRACT FROM AUTHOR]

We present a deep learning and simulation-based method to measure cortical capillary red blood cell (RBC) flux using Optical Coherence Tomography (OCT). This method is more accurate than the traditional peak-counting method and avoids any user parametrization, such as a threshold choice. We used data that was simultaneously acquired using OCT and two-photon microscopy to uncover the distribution of parameters governing the height, width, and inter-peak time of peaks in OCT intensity associated with the passage of RBCs. This allowed us to simulate thousands of time-series examples for different flux values and signal-to-noise ratios, which we then used to train a 1D convolutional neural network (CNN). The trained CNN enabled robust measurement of RBC flux across the entire network of hundreds of capillaries.

Optical coherence tomography angiography (OCTA) is a widely applied tool to image microvascular networks with high spatial resolution and sensitivity. Due to limited imaging speed, the artifacts caused by tissue motion can severely compromise visualization of the microvascular networks and quantification of OCTA images. In this article, we propose a deep‐learning‐based framework to effectively correct motion artifacts and retrieve microvascular architectures. This method comprised two deep neural networks in which the first subnet was applied to distinguish motion corrupted B‐scan images from a volumetric dataset. Based on the classification results, the artifacts could be removed from the en face maximum‐intensity‐projection (MIP) OCTA image. To restore the disturbed vasculature induced by artifact removal, the second subnet, an inpainting neural network, was utilized to reconnect the broken vascular networks. We applied the method to postprocess OCTA images of the microvascular networks in mouse cortex in vivo. Both image comparison and quantitative analysis show that the proposed method can significantly improve OCTA image by efficiently recovering microvasculature from the overwhelming motion artifacts. [ABSTRACT FROM AUTHOR]

Background: We present computational modeling of positron emission tomography radiotracer uptake with consideration of blood flow and interstitial fluid flow, performing spatiotemporally-coupled modeling of uptake and integrating the microvasculature. In our mathematical modeling, the uptake of fluorodeoxyglucose F-18 (FDG) was simulated based on the Convection–Diffusion–Reaction equation given its high accuracy and reliability in modeling of transport phenomena. In the proposed model, blood flow and interstitial flow are solved simultaneously to calculate interstitial pressure and velocity distribution inside cancer and normal tissues. As a result, the spatiotemporal distribution of the FDG tracer is calculated based on velocity and pressure distributions in both kinds of tissues. Results: Interstitial pressure has maximum value in the tumor region compared to surrounding tissue. In addition, interstitial fluid velocity is extremely low in the entire computational domain indicating that convection can be neglected without effecting results noticeably. Furthermore, our results illustrate that the total concentration of FDG in the tumor region is an order of magnitude larger than in surrounding normal tissue, due to lack of functional lymphatic drainage system and also highly-permeable microvessels in tumors. The magnitude of the free tracer and metabolized (phosphorylated) radiotracer concentrations followed very different trends over the entire time period, regardless of tissue type (tumor vs. normal). Conclusion: Our spatiotemporally-coupled modeling provides helpful tools towards improved understanding and quantification of in vivo preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Abstract Background The aim was to determine the relationship between bulbar conjunctival microcirculation and retinal microcirculation in a healthy population. Method A functional slit-lamp biomicroscope (FSLB) was used to measure blood flow velocity (BFV) and blood flow rate (BFR) in the conjunctiva while a retinal function imager (RFI) was used to measure macular BFV and BFR in the retina. One eye of each subject of 58 self-reported healthy subjects was imaged in the same session on the same day. Results The mean BFV in the venules of the conjunctiva was 0.49 ± 0.13 mm/s, which was significantly slower than that in the retinal arterioles (3.71 ± 0.78 mm/s, P 0.05). Conclusion The microcirculation in the retina appeared to be different from that in the conjunctiva.

Abstract Background The inter-visit variation of measuring bulbar conjunctival microvasculature and microcirculation needs to be considered when the results from multiple visits are interpreted. This study examined the inter-visit variability of measuring conjunctival microvasculature and microcirculation in habitual contact lens (HCL) wearers and non-contact lens (NCL) wearers. Methods Twenty-eight subjects were recruited including 13 HCL wearers (10 females and 3 males; mean age ± standard deviation, 25.8 ± 4.6 years) who had worn contact lenses on a daily basis for at least 3 years and 15 NCL wearers (10 females and 5 males, age 25.5 ± 4.0 years) were recruited. The temporal bulbar conjunctiva was imaged using a functional slit-lamp bio-microscope (FSLB) imaging system. FSLB imaging was performed in the morning when the HCL wearers did not wear their lenses. The measurements included conjunctival vessel diameter, vessel density, blood flow velocity and flow volume. In addition, conjunctival microvasculature was analyzed using monofractal (Dbox, representing vessel density) and multifractal (D0 representing vessel complexity) analyses. The repeated measurement was conducted at least one week after the first visit and both eyes of each participant were imaged. The coefficient of variation (CV) was calculated as the standard deviation of the differences between test and re-test then divided by the mean of the measurements. The intra-class correlation coefficient (ICC) was also calculated. Results No significant differences of all vascular measurements in both the right and left eyes were found between two groups (P > 0.05). Between two measurements on two different visits, the CV was from 2.4% (vessel density D0) to 63.5% (blood flow volume Q) in HCL wearers and from 3.4% (D0) to 40.6% (blood flow volume) in NCL wearers. The ICC was from 0.60 (vessel diameter) to 0.81 (axial blood flow velocity VA) in HCL wearers and from 0.44 (Q) to 0.68 (cross-sectional blood flow velocity VS) in NCL wearers. Conclusions The measurement variability of the vessel density of the bulbar conjunctiva appeared to have the smallest inter-visit variation. The measurement variability of the vasculature and circulation in HCL wearers were similar to that in NCL wearers.

A 3D microvascular network which was generated by 3D printing method was within the composite specimens. Healing efficiency of the composites was investigated using mechanical tensile and creep tests. The experimental results revealed that despite mechanical properties degradation in the specimens due to the presence of the embedded network, significant healing efficiency can be obtained at both room and elevated temperatures by the presented healing method. The maximum healing efficiency of 89% was obtained in tensile strength for the specimens, which were healed for 7 days. Moreover, creep behavior of the self-healing specimens showed promising results and the healing efficiency was 83% in creep rupture time of the composites at 90 °C. [ABSTRACT FROM AUTHOR]

Optical-resolution photoacoustic microscopy (OR-PAM) has been shown to be an excellent tool for high-resolution imaging of microvasculature, and quantitative analysis of the microvasculature can provide valuable information for the early diagnosis and treatment of various vascular-related diseases. In order to address the characteristics of weak signals, discontinuity and small diameters in photoacoustic microvascular images, we propose a method adaptive to the microvascular segmentation in photoacoustic images, including Hessian matrix enhancement and the morphological connection operators. The accuracy of our vascular segmentation method is quantitatively evaluated by the multiple criteria. To obtain more precise and continuous microvascular skeletons, an improved skeleton extraction framework based on the multistencil fast marching (MSFM) method is developed. We carried out in vivo OR-PAM microvascular imaging in mouse ears and subcutaneous hepatoma tumor model to verify the correctness and superiority of our proposed method. Compared with the previous methods, our proposed method can extract the microvascular network more completely, continuously and accurately, and provide an effective solution for the quantitative analysis of photoacoustic microvascular images with many small branches.

Abstract Background The differential diagnosis of optic disc edema at the acute phase can be challenging. OCT angiography (OCTA) is a new technology allowing the visualization of the peripapillary vascular network and optic disc capillaries. The peripapillary network alterations of glaucoma and chronic non-arteritic anterior ischemic optic neuropathy (NAION) were reported. However, no OCTA studies on acute optic disc edema from various causes. The aim of this project was to use OCTA to demonstrate the vascular changes the optic nerve head of various types of optic disc edema at the acute phase. Methods In this retrospective study, patients with non-arteritic anterior ischemic optic neuropathy (NAION), papillitis or papilledema were recruited. Each patient was imaged using the AngioPlex™ CIRRUS™ HD-OCT device(model 5000, Carl Zeiss Meditec, Inc., Dublin, USA) with a scanning area of 6 × 6 mm2 centered on the optic disc. A morphological analysis of the peripapillary network was performed. For some patients with unilateral optic disc edema, a quantitative analysis was performed using a swept-source OCT-A system (PLEX® Elite 9000, Carl Zeiss Meditec, Inc., Dublin, USA). Vessel perfusion density and flux index of the peripapillary area were calculated. Results Eight eyes with NAION (4 patients), 12 eyes with papillitis (6 patients) and 25 eyes with papilledema (13 patients) were imaged. The apparent disappearance or moderate pattern alteration of the peripapillary capillary vessels were observed in patients with NAION or papillitis, respectively. For papilledema, the capillaries at the surface of the optic disc were dilated and tortuous, but no peripapillary network pattern changes were observed. The quantitative analysis did not show any difference of peripapillary network between NAION and healthy eyes. For papillitis, the flux index was higher in inflammatory eyes compared to the healthy eyes in average (p = 0.03). Conclusion At the acute phase, the morphological analysis of OCT-A appeared to be more useful than the quantification analysis, facilitating the differentiation between the three kinds of ONH edema: ischemic, inflammatory and papilledema.

Optical-resolution photoacoustic microscopy (OR-PAM) has been shown to be an excellent tool for high-resolution imaging of microvasculature, and quantitative analysis of the microvasculature can provide valuable information for the early diagnosis and treatment of various vascular-related diseases. In order to address the characteristics of weak signals, discontinuity and small diameters in photoacoustic microvascular images, we propose a method adaptive to the microvascular segmentation in photoacoustic images, including Hessian matrix enhancement and the morphological connection operators. The accuracy of our vascular segmentation method is quantitatively evaluated by the multiple criteria. To obtain more precise and continuous microvascular skeletons, an improved skeleton extraction framework based on the multistencil fast marching (MSFM) method is developed. We carried out in vivo OR-PAM microvascular imaging in mouse ears and subcutaneous hepatoma tumor model to verify the correctness and superiority of our proposed method. Compared with the previous methods, our proposed method can extract the microvascular network more completely, continuously and accurately, and provide an effective solution for the quantitative analysis of photoacoustic microvascular images with many small branches. [ABSTRACT FROM AUTHOR]

The microvascular network is a simple but critical system that is responsible for a range of important biological mechanisms in the bodies of all animals. The ability to generate a functional microvessel not only makes it possible to engineer vital tissue of considerable size but also serves as a platform for biomedical studies. However, most of the current methods for generating microvessel networks in vitro use rectangular channels which cannot represent real vessels in vivo and have dead zones at their corners, hence hindering the circulation of culture medium. We propose a scaffold-wrapping method which enables fabrication of a customized microvascular network in vitro in a more biomimetic way. By integrating microelectromechanical techniques with thermal reflow, we designed and fabricated a microscale hemi-cylindrical photoresist template. A replica mold of polydimethylsiloxane, produced by casting, was then used to generate cylindrical scaffolds with biodegradable poly(lactide-co-glycolide) (PLGA). Human umbilical vein endothelial cells were seeded on both sides of the PLGA scaffold and cultured using a traditional approach. The expression of endothelial cell marker CD31 and intercellular junction vascular endothelial cadherin on the cultured cell demonstrated the potential of generating a microvascular network with a degradable cylindrical scaffold. Our method allows cells to be cultured on a scaffold using a conventional culture approach and monitors cell conditions continuously. We hope our cell-covered scaffold can serve as a framework for building large tissues or can be used as the core of a vascular chip for in vitro circulation studies.

Structural changes to microvascular networks are increasingly highlighted as markers of pathogenesis in a wide range of disease, e.g. Alzheimer's disease, vascular dementia and tumour growth. This has motivated the development of dedicated 3D imaging techniques, alongside the creation of computational modelling frameworks capable of using 3D reconstructed networks to simulate functional behaviours such as blood flow or transport processes. Extraction of 3D networks from imaging data broadly consists of two image processing steps: segmentation followed by skeletonisation. Much research effort has been devoted to segmentation field, and there are standard and widely-applied methodologies for creating and assessing gold standards or ground truths produced by manual annotation or automated algorithms. The Skeletonisation field, however, lacks widely applied, simple to compute metrics for the validation or optimisation of the numerous algorithms that exist to extract skeletons from binary images. This is particularly problematic as 3D imaging datasets increase in size and visual inspection becomes an insufficient validation approach. In this work, we first demonstrate the extent of the problem by applying 4 widely-used skeletonisation algorithms to 3 different imaging datasets. In doing so we show significant variability between reconstructed skeletons of the same segmented imaging dataset. Moreover, we show that such a structural variability propagates to simulated metrics such as blood flow. To mitigate this variability we introduce a new, fast and easy to compute super metric that compares the volume, connectivity, medialness, bifurcation point identification and homology of the reconstructed skeletons to the original segmented data. We then show that such a metric can be used to select the best performing skeletonisation algorithm for a given dataset, as well as to optimise its parameters. Finally, we demonstrate that the super metric can also be used to quickly identify how a particular skeletonisation algorithm could be improved, becoming a powerful tool in understanding the complex implication of small structural changes in a network., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this study, a novel multi-scale and multi-physics image-based computational model is introduced to assess the delivery of doxorubicin (Dox) loaded temperature-sensitive liposomes (TSLs) in the presence of hyperthermia. Unlike previous methodologies, this approach incorporates capillary network geometry extracted from images, resulting in a more realistic physiological tumor model. This model holds significant promise in advancing personalized medicine by integrating patient-specific tumor properties. The finite element method is employed to solve the equations governing intravascular and interstitial fluid flows, as well as the transport of therapeutic agents within the tissue. Realistic biological conditions and intricate processes like intravascular pressure, drug binding to cells, and cellular uptake are also considered to enhance the model's accuracy. The results underscore the significant impact of vascular architecture on treatment outcomes. Variation in vascular network pattern yielded changes of up to 38 % in the fraction of killed cells (FKCs) parameter under identical conditions. Pressure control of the parent vessels can also improve FKCs by approximately 17 %. Tailoring the treatment plan based on tumor-specific parameters emerged as a critical factor influencing treatment efficacy. For instance, changing the time interval between the administration of Dox-loaded TSLs and hyperthermia can result in a 48 % improvement in treatment outcomes. Additionally, devising a customized heating schedule led to a 20 % increase in treatment efficacy. Our proposed model highlights the significant effect of tumor characteristics and vascular network structure on the final treatment outcomes of the presented combination treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nonproportional RBC distribution is an important characteristic in microvascular networks, which can result in heterogeneity of oxygen supply that may cause ischemic death in severe cases. In this paper, we perform three-dimensional numerical simulations of a large number of RBCs in a microvascular network, by using a hybrid method of smoothed dissipative particle dynamic and immersed boundary method. The distribution of multiple RBCs in a T-bifurcation is first simulated as a validation study, and a reasonable agreement is observed both qualitatively and quantitatively on the RBC flux between our results and the previously published numerical and empirical results. Next, the distribution of a large number of RBCs in a microvascular network is investigated, including the effects of cell deformability, aggregation and tube hematocrit. The simulation results indicate that decreased deformability and increased aggregation strength have a similar effect on the RBC distribution: the large RBC flux becomes larger, but the small becomes smaller. A high hematocrit also causes a similar phenomenon that the RBCs are more apt to flow into a high RBC-flux branch, because they are arranged compactly into a rouleaux and difficultly broken up at a high hematocrit. These results imply that lower cell deformability, stronger aggregation or higher tube hematocrit would be conducive to the phase separation of hematocrit and plasma skimming processes in microcirculation. [ABSTRACT FROM AUTHOR]

Self-healing is a new strategy for crack defect which is the main reason for the failure of composites. As an extrinsic self-healing system, the microvascular network system is capable of multiple healing cycles and rapid healing of large area damage. However, the embedment of micropipe network will affect the performance of matrix material. In this article, a microvascular network of self-healing material is optimized using non-dominated sorting genetic algorithm II. Two objective functions head loss and void volume fraction are considered. Finite element analysis and Hardy Cross iteration are performed to achieve the quantization of objective functions. One hundred sixty-five optimized solutions were obtained, and the void volume fraction was within the limits of [4.19%, 5.13%], whereas the head loss was within the limits of [9.63×10−7 m, 6.51×10−6 m]. According to the optimization results, the network was prepared and tested to validate the design and feasibility. The test result shows that the void volume fraction of the prepared network is 3.77%, lower than the designed value 4.43% which has a little effect on the matrix material. The network is interconnected and the healing agent can flow freely in it. The embedded network does not reduce the performance of epoxy resin. The optimization of microvascular network balances the mechanical properties and self-repairing properties of the matrix material. [ABSTRACT FROM AUTHOR]

Functional and perfusable vascular network formation is critical to ensure the long-term survival and functionality of engineered tissues after their transplantation. Although several vascularization strategies have been reviewed in past, the significance of microvessel organization in three-dimensional (3D) scaffolds has been largely ignored. Advances in high-resolution microscopy and image processing have revealed that the majority of tissues including cardiac, skeletal muscle, bone, and skin contain highly organized microvessels that orient themselves to align with tissue architecture for optimum molecular exchange and functional performance. Here, we review strategies to develop highly organized and mature vascular networks in engineered tissues, with a focus on electromechanical stimulation, surface topography, micro scaffolding, surface-patterning, microfluidics and 3D printing. This review will provide researchers with state of the art approaches to engineer vascularized functional tissues for diverse applications. Vascularization is one of the critical challenges facing tissue engineering. Recent technological advances have enabled researchers to develop microvascular networks in engineered tissues. Although far from translational applications, current vascularization strategies have shown promising outcomes. This review emphasizes the most recent technological advances and future challenges for developing organized microvascular networks in vitro. The next critical step is to achieve highly perfusable, dense, mature and organized microvascular networks representative of native tissues. [ABSTRACT FROM AUTHOR]

• Developing a 2D fractal vascular tree model for a living tissue using finite element method. • Illustrating the effectiveness by comparison with the previously published works. • Proposing a novel technical strategy (i.e. pulsed-cryosurgery) for the impressive oblation of deep tumors and discussing its outcomes. • Prediction of iceball growth processing in the course of and after cryosurgery. • Presenting a thermal analysis of applying electric field on the nanoparticle-injected tissue in comparison with regular tissue. It is well-known that a successful cell destruction is a time-temperature-dependent process, so that the less temperature and the more freezing time, the more cell death will occur successfully. Hence, in order to be more effective ablation, the cryosurgery, whenever needed, should be done in a longer term and at a lower temperature in a more precise, controlled manner. To achieve the goal of targeted cancer therapy, we have proposed a "pulsed-cryosurgery" as a simple and impressive planning framework to provide conditions for the ablation of deep tumors with minimum damaging impact on normal tissue. To do so, a 2 D space-time-dependent model is developed with the help of the coupled Pennes' bio-heat, Navier-Stokes and Laplace equations to predict temperature distribution in the tumor, normal tissues and the microvascular network. Our results are in adequate harmony with the available ones in the literature. Furthermore, growing and shrinking of the ice-ball and lethal zone during and after the cryosurgery have been numerically studied. Subsequently, the effects of the heat generation produced by an electric field for hyperthermia treatment, the injection of nanofluid and spatial arrangement of cryoprobes on heat transfer in the biological tissues have been discussed. All the mentioned results have been supported and verified by illustrative simulations. [ABSTRACT FROM AUTHOR]

Purpose: The primary goal of this study was to estimate the value of β, the exponent in the power law relating changes of the transverse relaxation rate and intra‐extravascular local magnetic susceptibility differences as ΔR2∗∝(Δχ)β. The secondary objective was to evaluate any differences that might exist in the value of β obtained using a deoxyhemoglobin‐weighted Δχ distribution versus a constant Δχ distribution assumed in earlier computations. The third objective was to estimate the value of β that is relevant for methods based on susceptibility contrast agents with a concentration of Δχ higher than that used for BOLD fMRI calculations. Methods: Our recently developed model of real microvascular anatomical networks is used to extend the original simplified Monte‐Carlo simulations to compute β from the first principles. Results: Our results show that β=1 for most BOLD fMRI measurements of real vascular networks, as opposed to earlier predictions of β=1.5 using uniform Δχ distributions. For perfusion or fMRI methods based on contrast agents, which generate larger values for Δχ, β=1 for B0≤9.4 T, whereas at 14 T β can drop below 1 and the variation across subjects is large, indicating that a lower concentration of contrast agent with a lower value of Δχ is desired for experiments at high B0. Conclusion: These results improve our understanding of the relationship between R2* and the underlying microvascular properties. The findings will help to infer the cerebral metabolic rate of oxygen and cerebral blood volume from BOLD and perfusion MRI, respectively. [ABSTRACT FROM AUTHOR]

Objectives: Hypovascularisation is thought to play an important role in the pathogenesis of osteoradionecrosis. The objective of this study was to assess the microvascular system in the irradiated mandibular bone marrow.Materials and Methods: Mandibular bone biopsies were taken from 20 irradiated patients and 24 controls. Blood vessels were visualized using CD34 antibody stain to detect endothelial cells. The vascular density (VD) and vascular area fraction (VAF) were measured. Mean vessel lumen area, perimeter and diameter of the vessels were calculated for each vessel. A distinction was made between large and small vessels (cut-off point <400 µm2).Results: Vascular density and vascular area fraction were lower in the irradiated group. The mean vascular perimeter and mean vascular diameter were higher in samples with a local radiation dose of ≥50 Gy, whereas the percentage of small vessels was lower. Larger vessel perimeter is associated with higher radiation dose. A longer interval between biopsy and radiotherapy is associated with a larger mean vessel perimeter and a lower percentage of small vessels.Conclusions: Radiation dosages higher than 50 Gy mainly affect the smaller vessels. With increased time after irradiation, the share of smaller vessels in the mandibular bone marrow seems to decrease. In search of the exact mechanisms of irradiation damage and osteoradionecrosis of the mandible, the role of the microvascular system in the mandibular bone marrow should be further explored. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The effect of NO on smooth muscle cell contractility is crucial in regulating vascular tone, blood flow, and O2 delivery. Quantitative predictions for interactions between the NO production rate and the myogenic response for microcirculatory blood vessels are lacking. Methods: We developed a computational model of a branching microcirculatory network with four representative classes of resistance vessels to predict the effect of endothelium‐derived NO on the microvascular pressure‐flow response. Our model links vessel scale biotransport simulations of NO and O2 delivery to a mechanistic model of autoregulation and myogenic tone in a simplified microcirculatory network. Results: The model predicts that smooth muscle cell NO bioavailability significantly contributes to resting vascular tone of resistance vessels. Deficiencies in NO seen during hypoxia or ischemia lead to a decreased vessel diameter for all classes at a given intravascular pressure. At the network level, NO deficiencies lead to an increase in pressure drop across the vessels studied, a downward shift in the pressure‐flow curve, and a decrease in the effective range of the autoregulatory response. Conclusions: Our model predicts the steady state and transient behavior of resistance vessels to perturbations in blood pressure, including effects of NO bioavailability on vascular regulation. [ABSTRACT FROM AUTHOR]