Capillary Network Research Articles

Effective Rapid Fluorescence Lifetime Imaging of the Brain: A Novel Approach Using Upconversion Photoluminescence Lifetime Based on Gate-Width Acquisition.

The rapid lifetime imaging of upconversion photoluminescence is becoming increasingly popular in biosensing, anticounterfeiting, optical thermometry, and multiplex imaging. However, existing Rapid Lifetime Determination (RLD) techniques are limited in their ability to integrate contiguous, overlapping, and discrete windows into a single measurement, hindering accurate fluorescence lifetime retrieval. This study introduces a new data acquisition method using three adjustable gates in a single measurement to enhance resolution. We apply this method in rapid upconversion fluorescence lifetime imaging to visualize capillary networks and map pH levels based on intensity and lifetime differences in mouse brain vasculature. By enhancing brightness using NaYbF4@NaYF4,Er,Tm@NaYF4 nanoparticles, we achieve effective brain imaging. Monte Carlo simulations demonstrate a relative standard deviation of less than 0.4% for fluorescence durations spanning from 1 to 20 ns. This method provides a fast, high-contrast solution for multiplex brain imaging, addressing the limitations of slow data collection and poor accuracy in existing RLD techniques.

Evaluation of the effect of full-process blood glucose management on T2DM cataract patients based on visual electrophysiology and OCTA.

To investigate the difference in preoperative retinal function in patients with type 2 diabetes cataract (DC) without obvious retinopathy and to explore the clinical application of full blood glucose management for improving the postoperative vision in DC patients. This was a retrospective analysis in which we estimated the changes in visual electrophysiology (N75, P100, photopic flash electroretinogram(FERG), and scotopic FERG, paraoptic retinal nerve fibre layer thickness (pRNFL) and paraoptic radial capillary network blood flow density (ppVD) of type 2 diabetes (T2DM) patients at different phases of disease progression along with fasting blood glucose (FBG) and glycosylated haemoglobin (HbAlC) levels before and after DC surgery at Ziyang Central Hospital from January 2020 to December 2022. Additionally, trends in the above data throughout the entire process of glucose management intervention were examined. As the course of T2DM progressed, FBG and HbA1c increased, the N75 and P100 latency periods of patients gradually increased, and the values of photopic FERG, scotopic FERG, pRNFL, and ppVD gradually decreased at each postoperative time point. Moreover, the best corrected visual acuity(BCVA) of patients after surgery gradually decreased (P < 0.05). The BCVA of Group B (with full process blood glucose management) gradually stabilized at 1 month after surgery, and the BCVA of Group B was better than that of Group A at all time points after surgery. The results revealed that N75 and P100 in Group A were greater than those in Group B, whereas the photopic and scotopic FERG, pRNFL, and ppVD (%) values in Group A were lower than those in Group B. In addition, N75 and P100 in Group A gradually increased at various time points after surgery, whereas the photopic FERG, scotopic FERG, pRNFL, and ppVD (%) values gradually decreased. In the state of full blood glucose management, although N75 and P100 both reached their longest durations at one week after surgery, N75, the P100, photopic FERG, scotopic FERG, and pRNFL showed a gradually decreasing trend at 1 month and 3 months after surgery, whereas ppVD (%) gradually increased (P < 0.05). According to the results of the quantitative analysis of visual electrophysiology and OCTA, with the aggravation of diabetes, the retinal function of DC patients without obvious retinopathy tends to decrease, but full-process blood glucose management can effectively recover the retinal function of DC patients and improve visual quality after surgery.

An investigation into the microstructural evolution and shrinkage control in internally cured mortars with milkweed fibres

This study presented a significant advancement in the use of Milkweed (MW) fibres as internal curing agents in low water-to-cement (w/c) cementitious materials. The research focused on how different pre-treated MW fibres, with different composition, can impact internal curing efficacy in reducing autogenous shrinkage of cement mortars. In addition, the hydration behaviour and microstructural development were revealed using a series of tests including setting time, compressive strength, flexural strength, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA/DTG). A key finding of this study is the remarkable reduction in autogenous shrinkage, with using 0.1 % wt. pre-treated MW fibres leading to up to 28 % reduction at 7 days, compared to plain mortars. Furthermore, internal curing effect resulted in narrowing the compressive strength gap between the reference mixes and those with pre-treated MW fibres in the later stages of hydration. It was also found that the removal of hemicellulose through hybrid treatment can reduce the delay in the final setting time of cement from 45 minutes to 18 minutes. Additionally, while the incorporation of N- and HT-treated MW fibres had negligible effects on drying shrinkage, the inclusion of HY-treated MW fibres led to a 15 % increase in drying shrinkage at 7 days. This difference in behaviour was attributed to the presence of lignin in N- and HT-treated fibres. Lignin was found to play a crucial role in influencing the drying shrinkage, microstructural development, and mechanical properties of MW fibre-incorporated cementitious mixes. Acting as a protective barrier, lignin shielded the MW fibres from cement infiltration into their lumina. Moreover, it served as both a physical and chemical barrier, reducing moisture transport through the capillary network during drying. In conclusion, this study demonstrated the potential of using pre-treated MW fibres as internal curing agents to effectively reduce autogenous shrinkage, with minimal compromise in terms of the compressive strength of cementitious composites.

Barriers in Healthcare to the Use of Optical Coherence Tomography Angiography in Multiple Sclerosis.

Optical coherence tomography angiography (OCT-A) is a state-of-the-art imaging technique for the retinal vasculature to accurately segment the capillary network and assign it to retinal layers. OCT-A is a promising technique to better understand neurological diseases with visual system manifestations, such as multiple sclerosis (MS), and to identify and characterize vascular biomarkers. Initial studies suggested vascular changes in MS and its differential diagnoses such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Here we review clinical and technical aspects of OCT-A imaging and discuss the potential for the MS field as well as barriers that need to be overcome before OCT-A can be established in clinical application.

In Vitro Vascularization Improves In Vivo Functionality of Human Engineered Cardiac Tissues

Engineered human cardiac tissues hold great promise for disease modeling, drug development, and regenerative therapy. For regenerative applications, successful engineered tissue engraftment in vivo requires rapid vascularization and blood perfusion post-implantation. In the present study, we engineered highly functional, vascularized cardiac tissues (“cardiopatches”) by co-culturing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and endothelial cells (hiPSC-ECs) in optimized serum-free media. The vascularized cardiopatches displayed stable capillary networks over 4 weeks of culture, the longest reported in the field, while maintaining high contractile stress (>15 mN/mm2) and fast conduction velocity (>20 cm/s). Robustness of the method was confirmed using two distinct hiPSC-EC sources. Upon implantation into dorsal-skinfold chambers in immunocompromised mice, in vitro vascularized cardiopatches exhibited improved angiogenesis compared to avascular implants. Significant lumenization of the engineered human vasculature and anastomosis with host mouse vessels yielded the formation of hybrid human-mouse capillaries and robust cardiopatch perfusion by blood. Moreover, compared to avascular tissues, the implanted vascularized cardiopatches exhibited significantly higher conduction velocity and Ca2+ transient amplitude, longitudinally monitored in live mice for the first time. Overall, we demonstrate successful 4-week vascularization of engineered human cardiac tissues without loss of function in vitro, which promotes tissue functionality upon implantation in vivo. Statement of SignificanceComplex interactions between cardiac muscle fibers and surrounding capillaries are critical for everyday function of the heart. Tissue engineering is a powerful method to recreate functional cardiac muscle and its vascular network, which are both lost during a heart attack. Our study demonstrates in vitro engineering of dense capillary networks within highly functional engineered heart tissues that successfully maintain the structure, electrical, and mechanical function long-term. In mice, human capillaries from these engineered tissues integrate with host mouse capillaries to allow blood perfusion and support improved implant function. In the future, the developed vascularized engineered heart tissues will be used for in vitro studies of cardiac development and disease and as a potential regenerative therapy for heart attack.

Label-Free Non-Contact Vascular Imaging using Photon Absorption Remote Sensing.

Functional vascular imaging is a critical method for early detection and prevention of disease. Established non-contact vascular imaging techniques capture predominantly structural information. In this study, a novel non-contact label-free in vivo Photon Absorption Remote Sensing (PARS) microscope is developed for structural and functional vascular imaging. The presented in vivo PARS microscope captures the endogenous absorption of green (532nm) light to form a complete picture of vasculature and surrounding tissues. Imaging system repeatability is enhanced through robust transient absorption signal extraction, and state-of-the-art real-time alignment methods. Detailed imaging of vascular structure is demonstrated through in vivo microscopy of two established animal models: mouse ear and chicken embryo. Preliminary functional contrast is realized through video rate imaging of red blood cell dynamics in the capillary networks of chicken embryos. The presented in vivo PARS microscope successfully captures detailed structural and functional vascular contrast. This innovative non-contact label-free imaging technique holds promise as a tool for preventative medical care, as functional change often precedes structural change.

Computer model coupling hemodynamics and oxygen transport in the coronary capillary network: Pulsatile vs. non-pulsatile analysis

Background and Objective:Oxygen transport in the heart is crucial, and its impairment can lead to pathological conditions such as hypoxia, ischemia, and heart failure. However, investigating oxygen transport in the heart using in vivo measurements is difficult due to the small size of the coronary capillaries and their deep embedding within the heart wall. Methods:In this study, we developed a novel computational modeling framework that integrates a 0-D hemodynamic model with a 1-D mass transport model to simulate oxygen transport in/across the coronary capillary network. Results:The model predictions agree with analytical solutions and experimental measurements. The framework is used to simulate the effects of pulsatile vs. non-pulsatile behavior of the capillary hemodynamics on oxygen-related metrics such as the myocardial oxygen consumption (MVO2) and oxygen extraction ratio (OER). Compared to simulations that consider (physiological) pulsatile behaviors of the capillary hemodynamics, the OER is underestimated by less than 9% and the MVO2 is overestimated by less than 5% when the pulsatile behaviors are ignored in the simulations. Statistical analyses show that model predictions of oxygen-related quantities and spatial distribution of oxygen without consideration of the pulsatile behaviors do not significantly differ from those that considered such behaviors (p-values >0.05). Conclusions:This finding provides the basis for reducing the model complexity by ignoring the pulsatility of coronary capillary hemodynamics in the computational framework without a substantial loss of accuracy when predicting oxygen-related metrics.

Enhancing human capillary tube network assembly and maturation through upregulated expression of pericyte-derived TIMP-3.

In this study, we identify and characterize new molecular determinants that optimize human capillary tube network assembly. Our lab has previously reported a novel, serum free-defined 3D co-culture model using human endothelial cells (ECs) and human pericytes whereby EC-lined tubes form and co-assemble with pericytes, but when these cultures are maintained at or beyond 5 days, tubes become progressively wider and unstable. To address this issue, we generated novel human pericytes that carry a tissue inhibitor of metalloproteinase (TIMP)-3 transgene which can be upregulated following doxycycline addition. EC-pericyte co-cultures established in the presence of doxycycline demonstrated marked enhancement of capillary network assembly including dramatic narrowing of capillary tube widths to an average of 8µm (physiologic capillary tube width), increased tube lengths, increased tube branching, and robust stimulation of basement membrane matrix assembly, particularly with collagen type IV and fibronectin deposition compared to controls. These substantial changes depend not only on induction of pericyte TIMP-3, but also on recruitment of pericytes to EC tubes. Blockade of pericyte recruitment prevents these dramatic capillary network alterations suggesting that EC-pericyte interactions and induction of pericyte TIMP-3 are necessary together to coordinate and facilitate capillary assembly and maturation. Overall, this work is critical for our basic understanding of capillary formation, but also for the ability to reproducibly generate stabilized networks of capillary tubes.

Collagen I Microfiber Promotes Brain Capillary Network Formation in Three–Dimensional Blood–Brain Barrier Microphysiological Systems

Collagen I Microfiber Promotes Brain Capillary Network Formation in Three–Dimensional Blood–Brain Barrier Microphysiological Systems

Anisotropic Hollow Structure with Chemotaxis Enabling Intratumoral Autonomic Therapy.

Effective intratumoral drug penetration is pivotal for successful cancer treatment. However, due to the disrupted capillary networks and poor perfusion in solid tumors, there exist challenges to realize autonomous directional drug penetration and controlled drug release within the tumor. Considering the specificity of glucose within tumor tissue, we draw inspiration from nature and engineer asymmetrical hollow structures exhibiting chemotaxis towards high glucose levels. By incorporating multiple shells into these structures, we enhance the local chemical concentration gradients, thereby improving cellular uptake and precise targeting. The advantages of anisotropic hollow multishell structure (a-HoMS) can be reflected from the diffusion coefficient and directivity, which increase by 73.4% and 265% respectively compared to conventional isotropic hollow spheres, achieving the most linear movement while ensuring the speed of movement. Furthermore, the multi-level porosity and temporal-spatial order of a-HoMS enable sequential drug delivery that inhibits angiogenesis with inducing cell apoptosis. After the eradication of localized tumor cells, the a-HoMS can automatically migrate to the alive tumor cells under the glucose gradient, inducing another cycle of drug delivery and chemotaxis, resulting in excellent antitumor efficacy. These anisotropic HoMS demonstrate intelligence, adaptability, and precision in tumor therapy, providing valuable insights for programmable treatment within tissues.

Anisotropic Hollow Structure with Chemotaxis Enabling Intratumoral Autonomic Therapy

Effective intratumoral drug penetration is pivotal for successful cancer treatment. However, due to the disrupted capillary networks and poor perfusion in solid tumors, there exist challenges to realize autonomous directional drug penetration and controlled drug release within the tumor. Considering the specificity of glucose within tumor tissue, we draw inspiration from nature and engineer asymmetrical hollow structures exhibiting chemotaxis towards high glucose levels. By incorporating multiple shells into these structures, we enhance the local chemical concentration gradients, thereby improving cellular uptake and precise targeting. The advantages of anisotropic hollow multishell structure (a‐HoMS) can be reflected from the diffusion coefficient and directivity, which increase by 73.4% and 265% respectively compared to conventional isotropic hollow spheres, achieving the most linear movement while ensuring the speed of movement. Furthermore, the multi‐level porosity and temporal‐spatial order of a‐HoMS enable sequential drug delivery that inhibits angiogenesis with inducing cell apoptosis. After the eradication of localized tumor cells, the a‐HoMS can automatically migrate to the alive tumor cells under the glucose gradient, inducing another cycle of drug delivery and chemotaxis, resulting in excellent antitumor efficacy. These anisotropic HoMS demonstrate intelligence, adaptability, and precision in tumor therapy, providing valuable insights for programmable treatment within tissues.

Endothelial Beta 1 Integrins are Necessary for Microvascular Function and Glucose Uptake.

Microvascular insulin delivery to myocytes is rate limiting for the onset of insulin-stimulated muscle glucose uptake. The structural integrity of capillaries of the microvasculature is regulated, in part, by a family of transmembrane adhesion receptors known as integrins, which are composed of an α and β subunit. The integrin β1 (itgb1) subunit is highly expressed in endothelial cells (EC). EC itgb1 is necessary for the formation of capillary networks during embryonic during development and its knockdown blunts the reactive hyperemia that manifests during ischemia reperfusion. We investigated the contribution of EC itgb1 in microcirculatory function and glucose uptake with emphasis in skeletal muscle. We hypothesized that loss of EC itgb1 would impair microvascular hemodynamics and glucose uptake during insulin stimulation, creating 'delivery'-mediated insulin resistance. An itgβ1 knockdown mouse model was developed to avoid lethality of embryonic gene knockout and the deteriorating health resulting from early post-natal inducible gene deletion. Mice with (itgb1fl/flSCLcre) and without (itgb1fl/fl) tamoxifen inducible stem cell leukemia cre recombinase (SLCcre) expression at 10 days post cre induction had comparable exercise tolerance and pulmonary and cardiac functions. Using robust in vivo experimental platforms (i.e., intravital microscopy and hyperinsulinemic-euglycemic clamp), we show that itgb1fl/flSCLcre mice compared to itgb1fl/fl littermates have, i) deficits in capillary flow rate, flow heterogeneity, and capillary density; ii) impaired insulin-stimulated glucose uptake despite sufficient transcapillary insulin efflux; and iii) reduced insulin-stimulated glucose uptake due to perfusion-limited glucose delivery. Thus, EC itgb1 is necessary for microcirculatory function and to meet the metabolic challenge of insulin stimulation.

Spatio-temporal instabilities of blood flow in a model capillary network

Spatio-temporal instabilities of blood flow in a model capillary network

The Complexities of Orbital Arteriovenous Malformations: A Systematic Review of Clinical Features and Treatment Approaches.

The orbital vascular malformations are very rare congenital lesions characterized by a connection directly between arteries and veins, thus bypassing the capillary network. These lesions may be associated with clinical features ranging from mild proptosis to vision-threatening conditions like visual loss and elevated intraocular pressure.Despite advances in imaging and treatment strategies, the management of orbital arteriovenous malformations (AVMs) still remains daunting because of the high risk of complications, including hemorrhage and incomplete resection. Thissystematic review was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A detailed search of the major databases such as PubMed and Scopus was performed using the keywords "Ocular OR orbit AND arteriovenous malformations OR AVM" without specifying the date. All case reports, case series, and observational studies reporting the diagnosis, treatment, and outcome of patients with orbital AVM were included. Data extraction was focused on clinical presentations, diagnostic modalities, treatment interventions, and outcomes; narrative synthesis was done due to heterogeneity in the studies. This review contains 27 case reports, where the number of patients ranged between three years and 75 years with a mean age of 34 years. The majority of the patients were males constituting 66%. The common clinical features include proptosis in 16 cases, visual loss in 12 cases, and chemosis in seven cases. Most of the patients underwent surgical resection and embolization of the malformations. In most of the cases, surgical resection was uneventful; however, a few cases with high risks showed hemorrhage and loss of vision as complications. Conservative management was also effective in certain stable or asymptomatic cases. Orbital vascular malformations include complex diagnostic and therapeutic challenges due to the complex anatomy of the orbit and the high risk of serious complications. This systematic review aimed at presenting the clinical features, diagnostic challenges, and treatment outcomes of orbital arteriovenous malformations for a better management strategy.Further research is required in the refinement of treatment protocols, especially regarding high-flow lesions, and a critical look at improving long-term efficacy.

The eATP/P2×7R Axis Drives Quantum Dot-Nanoparticle Induced Neutrophil Recruitment in the Pulmonary Microcirculation.

Exposure to nanoparticles (NPs) is frequently associated with adverse cardiovascular effects. In contrast, NPs in nanomedicine hold great promise for precise lung-specific drug delivery, especially considering the extensive pulmonary capillary network that facilitates interactions with bloodstream-suspended particles. Therefore, exact knowledge about effects of engineered NPs within the pulmonary microcirculation are instrumental for future application of this technology in patients. To unravel the real-time dynamics of intravenously delivered NPs and their effects in the pulmonary microvasculature, we employed intravital microscopy of the mouse lung. Only PEG-amine-QDs, but not carboxyl-QDs triggered rapid neutrophil recruitment in microvessels and their subsequent recruitment to the alveolar space and was linked to cellular degranulation, TNF-α, and DAMP release into the circulation, particularly eATP. Stimulation of the ATP-gated receptor P2X7R induced expression of E-selectin on microvascular endothelium thereby mediating the neutrophilic immune response. Leukocyte integrins LFA-1 and MAC-1 facilitated adhesion and decelerated neutrophil crawling on the vascular surface. In summary, this study unravels the complex cascade of neutrophil recruitment during NP-induced sterile inflammation. Thereby we demonstrate novel adverse effects for NPs in the pulmonary microcirculation and provide critical insights for optimizing NP-based drug delivery and therapeutic intervention strategies, to ensure their efficacy and safety in clinical applications.

Thermal performance analysis of supporting column ultra-thin vapor chamber with graded microgroove

To analyze the thermal behavior of a graded microgroove ultra-thin vapor chamber with supporting column, a three-dimensional steady-state numerical model coupled with graded capillary force network, which involves hydraulic and heat transfer on hydraulic and heat transfer performance on ultra-thin vapor chamber with different supporting column sizes. This model considers the influence of supporting column with varying diameters and intervals on liquid flow and temperature distribution, as well as the effects of a graded capillary force network on heat transfer limit of ultra-thin vapor chamber. The numerical results show that the additional heat transfer provided by the central support column causes an outward shift in the saturation temperature of vapor, creating a new liquid reflux path at the condensation surface. The accuracy of the model is verified by the preparation of ultra-thin vapor chamber with a graded microgroove a graded microgroove. Compared with the experimental results on conventional microgrooves, graded microgrooves can improve the heat transfer limit by 29.3%. According to the theoretical analysis model, the graded capillary force network can effectively resist incremental increases in vapor pressure drop, enhancing the efficiency of gas–liquid circulation of ultra-thin vapor chamber.

Chronic Peroxisome Proliferator-Activated Receptor α/γ and Cannabinoid Receptor 2 Agonist Treatments Attenuated Visceral Adipose Tissue (VAT)–Derived Extracellular Vesicle–Related VAT and Intestinal Abnormalities in Nonalcoholic Steatohepatitis Mice

This study explores the mechanisms and combined effects of chronic peroxisome proliferator-activated receptor (PPAR)α/γ and cannabinoid receptor 2 (CB2R) agonists on visceral adipose tissue (VAT)-derived extracellular vesicle (EVs) release and associated systemic/VAT inflammation, decreased VAT capillary density/fibrosis, and intestinal inflammation/hyperpermeability in nonalcoholic steatohepatitis (NASH) mice. NASH mice receiving 1 month of PPARα/γ agonist aleglitazar (10 mg/kg/day), CB2R agonist JWH015 (3 mg/kg/day) alone or combined. High EV release from VAT of NASH mice was associated with severe systemic/VAT/intestinal inflammation, reduced capillary network of VAT, and intestinal hyperpermeability. Combined JWH015 with aleglitazar treatment significantly suppressed HFD-induced obesity/adiposity, inhibited VAT expansion, reduced VAT inflammation/fibrosis, normalized VAT capillary network, and attenuated intestinal mucosal injury, inflammation, and hyperpermeability in NASH+aleg+JWH015 mice. The inhibition of AT-derived EV release and hypoxia inducible factor (HIF)1α levels in AT-derived EV, normalization of CB2R, PPARα, PPARγ, PPARγ1, PPARγ2, tight junction proteins, VEGF/CD31 expression, and downregulations of HIF1α, MCP-1 and TGFβ1 were observed in the VAT and intestine of the NASH+aleg+jwh015 group. In vitro experiments revealed that PPARα/γ and CB2R activation attenuated NASH AT-derived EV (EVnash)-induced pathogenic changes in the J774/SVEC4-10/Caco2 /3T3-L1 cell system. This study suggested that VAT-derived EVs contribute to the pathogenesis of NAFLD and that combined PPARα/γ and CB2R agonist treatment reduces VAT-released EV release and HIF1/MCP-1 signals to ameliorate hepatic steatosis and VAT/intestine abnormalities of NASH mice.

Matrix Stiffness of GelMA Hydrogels Regulates Lymphatic Endothelial Cells toward Enhanced Lymphangiogenesis.

Lymphatic vessel regeneration is crucial for various tissue engineering strategies, particularly in resolving inflammation and restoring tissue homeostasis. In our study, we focused on investigating how hydrogel matrix stiffness influences lymphatic endothelial cells (LECs) in promoting lymphatic vessel regeneration. Gelatin methacrylate (GelMA) was chosen as our biomaterial due to its versatility in tissue engineering and biofabrication. We fabricated GelMA hydrogels at concentrations of 5, 7.5, and 15% (w/v) with corresponding Young's modulus values of 1.55 kPa (soft matrix), 12.02 kPa (medium matrix), and 48.50 kPa (stiff matrix). Among these, the 7.5% GelMA hydrogel exhibited optimal stiffness for promoting lymphangiogenesis. LECs seeded either on the hydrogel surface or within spontaneously formed a more stable lymphatic capillary network compared with other GelMA formulations. Furthermore, we investigated the enhancement of lymphangiogenesis by incorporating VEGF-C into the GelMA hydrogel, leveraging the synergistic effects of mechanical and chemical cues. Our results underscored the critical role of FAK-phosphorylation in this process; treatment with an FAK-specific inhibitor prevented the formation of tube-like structures by LECs and attenuated the expression of lymphatic markers. Overall, our findings highlight how the mechanical and chemical cues provided by GelMA hydrogels can effectively regulate LEC behavior toward enhanced lymphangiogenesis via the integrin/FAK mechanotransduction pathway. This study proposes a promising strategy for developing hydrogel-based scaffolds or bioinks tailored to promote lymphatic vessel regeneration in therapeutic applications.

Serum Amyloid A1 Damages the Peritubular Capillary Network and Promotes Kidney Fibrosis

Serum Amyloid A1 Damages the Peritubular Capillary Network and Promotes Kidney Fibrosis

The Cerebrovascular Side of Plasticity: Microvascular Architecture across Health and Neurodegenerative and Vascular Diseases.

The delivery of nutrients to the brain is provided by a 600 km network of capillaries and microvessels. Indeed, the brain is highly energy demanding and, among a total amount of 100 billion neurons, each neuron is located just 10-20 μm from a capillary. This vascular network also forms part of the blood-brain barrier (BBB), which maintains the brain's stable environment by regulating chemical balance, immune cell transport, and blocking toxins. Typically, brain microvascular endothelial cells (BMECs) have low turnover, indicating a stable cerebrovascular structure. However, this structure can adapt significantly due to development, aging, injury, or disease. Temporary neural activity changes are managed by the expansion or contraction of arterioles and capillaries. Hypoxia leads to significant remodeling of the cerebrovascular architecture and pathological changes have been documented in aging and in vascular and neurodegenerative conditions. These changes often involve BMEC proliferation and the remodeling of capillary segments, often linked with local neuronal changes and cognitive function. Cerebrovascular plasticity, especially in arterioles, capillaries, and venules, varies over different time scales in development, health, aging, and diseases. Rapid changes in cerebral blood flow (CBF) occur within seconds due to increased neural activity. Prolonged changes in vascular structure, influenced by consistent environmental factors, take weeks. Development and aging bring changes over months to years, with aging-associated plasticity often improved by exercise. Injuries cause rapid damage but can be repaired over weeks to months, while neurodegenerative diseases cause slow, varied changes over months to years. In addition, if animal models may provide useful and dynamic in vivo information about vascular plasticity, humans are more complex to investigate and the hypothesis of glymphatic system together with Magnetic Resonance Imaging (MRI) techniques could provide useful clues in the future.