A Dynamically Tunable,Bioinspired Micropatterned Surface Regulates Vascular Endothelial and Smooth Muscle Cells Growth at Vascularization

Regulation of the growth of vascular endothelial cells (ECs) and smooth muscle cells (SMCs) with artificial vascular grafts at vascularization is well‐known to regenerate functional blood vessels for treating cardiovascular disease; however, little research has been published on this subject. Here, a novel polymer vascular graft is presented, whose inner surface contains an assembled circular microgroove pattern decorated with a combination of concentric circular microgrooves and radial, straight microgrooves inspired by the orientation of SMCs and ECs in natural tissues. The surface micropatterns can produce dynamically tunable variations via the thermally switched shape memory. The results from the in vitro EC/SMC co‐cultures reveal that the surface micropatterns have a great capacity to regulate the specific distribution of ECs/SMCs because the ECs grow along the radial, straight microgrooves and the SMCs grow along concentric circular microgrooves. The in vivo vascularization is further analyzed by implanting the vascular graft in the rabbit carotid artery. Both histological analysis and immunofluorescence staining demonstrate that it is capable of highly effectively capturing ECs and SMCs in the blood and subsequent regeneration of new blood vessels. Therefore, this study opens a new possibility for regenerating neovessels to replace and repair damaged vessels for cardiovascular diseases treatment.     

Micro‐vascular imaging experiences of time‐of‐flight MRA at 7T for cerebrovascular diseases

Surgical or endovascular approaches have proved effective for large‐vessel diseases over the past decade. However, approaches for small vessel diseases are unlikely to be accomplished by those for large vessels and only few have been applied, because it is hard to access to those small vessels and one could not directly delineate the affected small vessels due to a lack of detection modalities. This study is to examine patients with vascular diseases using ultra‐high field 7T MRI with conventional time‐of‐flight (TOF) sequence, 3D fast low‐angle shot (FLASH) gradient‐echo. We have evaluated several radio‐frequency (RF) coils to find the optimal one for 7T magnetic resonance angiography (MRA), especially for micro‐vascular imaging. We have conducted several comparison studies with vascular disease patients. The results showed that micro‐vessels such as lenticulostriate arteries in the subjects with risk factors like hypertension or stroke patients were significantly less than in the healthy subjects. 7T MRA images in steno‐occlusive patients also showed clearly numerous collateral vessels not visible by 1.5T or 3T MRA. Furthermore, 7T MRA images were comparable to those obtained by digital subtraction angiography (DSA), particularly for micro‐vascular imaging. In this article, we would like to share the clinical experiences on 7T MRA that vascular images of 7T MRA were superior to conventional angiography images including 1.5T and 3T MRA, and even comparable to DSA. We also expect that further technical development and clinical applications of 7T MRA would be a clinically important diagnostic tool, in terms of an early detection of the stroke in a totally non‐invasive manner. © 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 121–128, 2014     

Bioinspired,Anticoagulative, 19F MRI-Visualizable Bilayer Hydrogel Tubes as High Patency Small-Diameter Vascular Grafts

The clinical patency of small-diameter vascular grafts (SDVGs) (ID < 6 mm) is limited, with the formation of mural thrombi being a major threat of this limitation. Herein, a bilayered hydrogel tube based on the essential structure of native blood vessels is developed by optimizing the relation between vascular functions and the molecular structure of hydrogels. The inner layer of the SDVGs comprises a zwitterionic fluorinated hydrogel, avoiding the formation of thromboinflammation-induced mural thrombi. Furthermore, the position and morphology of the SDVGs can be visualized via ¹⁹F/¹H magnetic resonance imaging. The outer poly(N-acryloyl glycinamide) hydrogel layer of SDVGs provides matched mechanical properties with native blood vessels through the multiple and controllable intermolecular hydrogen-bond interactions, which can withstand the accelerated fatigue test under pulsatile radial pressure for 380 million cycles (equal to a service life of 10 years in vivo). Consequently, the SDVGs exhibit higher patency (100%) and more stable morphology following porcine carotid artery transplantation for 9 months and rabbit carotid artery transplantation for 3 months. Therefore, such a bioinspired, antithrombotic, and visualizable SDVG presents a promising design approach for long-term patency products and great potential of helping patients with cardiovascular diseases.     

Longitudinal micro-incision creation prior to balloon angioplasty for treatment of arteriovenous access dysfunction in a real-world patient population: 6-month cohort analysis

Introduction

Routine hemodialysis depends on well-functioning vascular access. In the event of vascular access dysfunction, percutaneous transluminal balloon angioplasty (PTA) is conducted to restore patency. Although an angioplasty procedure can provide an excellent immediate result by opening the access to allow dialysis to continue, the long-term patency rates are less than satisfactory. The goal of this study was to assess the outcomes of patients who underwent a novel vessel preparation via longitudinal, controlled-depth micro-incisions prior to PTA.

Methods

This multicenter, prospective, observational registry enrolled hemodialysis patients scheduled to undergo PTA of their arteriovenous fistula or graft due to clinical or hemodynamic abnormalities. A primary endpoint was anatomic success, defined as angiographic confirmation of <30% residual stenosis post-procedure without an adverse event. Additional assessments included device technical success, clinical success, freedom from target lesion revascularization, target lesion primary patency, and circuit primary patency at 6 months.

Findings

A total of 148 lesions were treated with the FLEX Vessel Prep™ System (FLEX VP) prior to PTA in 114 subjects at eight clinical sites. Target lesions were 21 ± 25 mm in length with mean pre-procedure stenosis of 75.2% ± 4.7%. Five procedural complications were recorded without serious adverse events. Two subjects did not complete the follow-up evaluation. Target lesion primary patency across all subjects at 6-months was 62.2% with mean freedom from target lesion revascularization of 202.7 days. Target lesion primary patency and freedom from target lesion revascularization for AVF cases (n = 72) were 67.5% and 212.9 days, respectively. Target lesion primary patency and freedom from target lesion revascularization for AVGs (n = 42) were 52.4% and 183.3 days, respectively. In cases treating AVF cephalic arch stenosis (n = 25), 6-month target lesion primary patency was 70.6% and freedom from target lesion revascularization was 213.4 days.

Discussion

This FLEX-AV registry demonstrates safety and effectiveness, notably in the cephalic arch and AVGs, when FLEX VP is used prior to PTA for treatment of vascular access dysfunction in a population of end-stage renal disease subjects.     

Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow?

Intimal hyperplasia (IH) is a leading cause of obstruction of vascular interventions, including arterial stents, bypass grafts and arteriovenous grafts and fistulae. Proposals to account for arterial stent-associated IH include wall damage, low wall shear stress (WSS), disturbed flow and, although not widely recognized, wall hypoxia. The common non-planarity of arterial geometry and flow, led us to develop a bare-metal, nitinol, self-expanding stent with three-dimensional helical-centreline geometry. This was deployed in one common carotid artery of healthy pigs, with a straight-centreline, but otherwise identical (conventional) stent deployed contralaterally. Both stent types deformed the arteries, but the helical-centreline device additionally deformed them helically and caused swirling of intraluminal flow. At sacrifice, one month post stent deployment, histology revealed significantly less IH in the helical-centreline than straight-centreline stented vessels. Medial cross-sectional area was not significantly different in helical-centreline than straight-centreline stented vessels. By contrast, luminal cross-sectional area was significantly larger in helical-centreline than straight-centreline stented vessels. Mechanisms considered to account for those results include enhanced intraluminal WSS and enhanced intraluminal blood–vessel wall mass transport, including of oxygen, in the helical-centreline stented vessels. Consistent with the latter proposal, adventitial microvessel density was lower in the helical-centreline stented than straight-centreline stented vessels.     

Magnetic resonance imaging-based computational modelling of blood flow and nanomedicine deposition in patients with peripheral arterial disease

Peripheral arterial disease (PAD) is generally attributed to the progressive vascular accumulation of lipoproteins and circulating monocytes in the vessel walls leading to the formation of atherosclerotic plaques. This is known to be regulated by the local vascular geometry, haemodynamics and biophysical conditions. Here, an isogeometric analysis framework is proposed to analyse the blood flow and vascular deposition of circulating nanoparticles (NPs) into the superficial femoral artery (SFA) of a PAD patient. The local geometry of the blood vessel and the haemodynamic conditions are derived from magnetic resonance imaging (MRI), performed at baseline and at 24 months post intervention. A dramatic improvement in blood flow dynamics is observed post intervention. A 500% increase in peak flow rate is measured in vivo as a consequence of luminal enlargement. Furthermore, blood flow simulations reveal a 32% drop in the mean oscillatory shear index, indicating reduced disturbed flow post intervention. The same patient information (vascular geometry and blood flow) is used to predict in silico in a simulation of the vascular deposition of systemically injected nanomedicines. NPs, targeted to inflammatory vascular molecules including VCAM-1, E-selectin and ICAM-1, are predicted to preferentially accumulate near the stenosis in the baseline configuration, with VCAM-1 providing the highest accumulation (approx. 1.33 and 1.50 times higher concentration than that of ICAM-1 and E-selectin, respectively). Such selective deposition of NPs within the stenosis could be effectively used for the detection and treatment of plaques forming in the SFA. The presented MRI-based computational protocol can be used to analyse data from clinical trials to explore possible correlations between haemodynamics and disease progression in PAD patients, and potentially predict disease occurrence as well as the outcome of an intervention.     

The effects of nonsymmetry in a branching flow network

A planar flow network consisting of successive generations of bifurcating vessels located downstream from a single mother vessel containing an incident fully developed flow is investigated. The theory and analysis developed which are for relatively thin vessels apply to small, medium or large networks. Although each successive bifurcation is in effect from a new mother vessel to two daughters, the networked system splits these into different types of bifurcation, the middle ones being inertial and the edge ones being viscous–inviscid in view of the wall conditions. The influences of network shapes, topology and end-pressure differences on the flow ahead of and inside the network are examined. Distinct local and global forms of upstream influence are active. The effects are especially marked in terms of non-symmetry, which leads to a global upstream influence, displaces the whole incident flow and particularly affects the motions near the outermost walls; there the non-symmetrical effects govern the induced wall shear stress and pressure and the solution dependence is very sensitive because of the realistic incident flow. Results from lattice-Boltzmann simulations are also described, and comparisons are then made with the theory and analysis. Pressure and shape control are considered in detail.     

Heparin-modified small-diameter nanofibrous vascular grafts

Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter vascular grafts. Here we produced 1-mm diameter vascular grafts with nanofibrous structure via electrospinning, and successfully modified the nanofibers by the conjugation of heparin using di-amino-poly(ethylene glycol) (PEG) as a linker. Antithrombogenic activity of these heparin-modified scaffolds was confirmed in vitro. After 1 month implantation using a rat common carotid artery bypass model, heparin-modified grafts exhibited 85.7% patency, versus 57.1% patency of PEGylated grafts and 42.9% patency of untreated grafts. Post-explant analysis of patent grafts showed complete endothelialization of the lumen and neovascularization around the graft. Smooth muscle cells were found in the surrounding neo-tissue. In addition, greater cell infiltration was observed in heparin-modified grafts. These findings suggest heparin modification may play multiple roles in the function and remodeling of nanofibrous vascular grafts, by preventing thrombosis and maintaining patency, and by promoting cell infiltration into the three-dimensional nanofibrous structure for remodeling.     

Use of a "composite" vascular access graft in a young child on hemodialysis

Although arterio-venous fistulae (AVF) are currently considered to be the first choice of permanent vascular access for hemodialysis, there are some patients who are not candidates for fistulae and synthetic grafts provide other options. The Thoratec (Vectra) polyurethane vascular access graft is a new prosthetic graft that may be cannulated within days of insertion due to "self-sealing" properties. However, a tendency for kinking at the suture site due to the strong elasticity of this graft, leading to undesirable complications such as thrombosis, have been reported. We describe a surgical modification of the anastomosis by interposing a segment of expanded polytetrafluoroethylene graft (ePTFE, Venaflo) between the native vessels and the polyurethane graft sections in a pediatric patient. This modification may overcome the kinking complication associated with use of the polyurethane graft and the resulting thrombosis.     

Arteriovenous fistula for the 80 years and older patients on hemodialysis: Is it worth it?

Over the last years, the proportion of patients older than 80 years with end‐stage renal disease has been constantly growing. Arteriovenous fistula (AVF) is known as the best vascular access for hemodialysis, but evidence for its added value is lacking for elderly. We retrospectively identified new vascular access (AVF and central venous catheter) created or installed between June 2005 and June 2008 in patients 80 years and older and in patients between 50 and 60 years. For every new AVF, we calculated primary failure, primary and secondary patency durations. Fifty‐five and 57 patients had a new vascular access in the >80 years old and 50 to 60 years old groups. Among these, 25 and 41 were new AVF in the older and younger groups. Primary failure was more frequent in elderly than in the younger (40% vs. 17%, P = 0.04). Primary patency was not significantly different in both groups (P = 0.06). Secondary patency was shorter in elderly (P = 0.005). Among the older group, the presence of an AVF was not associated with a difference in mortality (46% vs. 60%, P = 0.28), whereas there was a lower mortality in the younger group with AVF (12% vs. 43% P = 0.008). These results indicate lower patency duration in very elderly patients compared to middle‐aged patients. Without leading to the exclusion of patients over 80 years old for AVF creation, it might reinforce the need of a careful selection and evaluation in this population prior to referral.     

In vivo measurement of blood flow in a micro‐scale stenosis model generated by laser photothermal blood coagulation

Blood flow in a stenosed vessel is one of the most important issues, because it is closely related to the outbreak of circulatory diseases. To overcome the technological limitations encountered in the haemodynamic studies using in vitro stenosis models, the authors induced a stenosed flow model in the extraembryonic vessels of a chicken embryo. Blood was coagulated by laser irradiation to artificially form a stenosis on the designated spot in a straight blood vessel. Owing to photothermal coagulation of red blood cells (RBCs), the blood is denatured and a stable blood coagulum is induced in the vessel. The blood coagulum adheres firmly and stably on the vessel wall without any size variation. It disturbs the on‐coming blood flow significantly. To investigate the haemodynamic characteristics of the blood flow in the stenosed vessel, a micro particle image velocimetry technique was employed using RBCs as tracers to measure the spatial distributions of velocity vectors, streamlines and shear rate. The present simple modelling of in vivo stenosis would be useful for investigating the basic haemodynamic mechanisms underlying circulatory vascular diseases.Inspec keywords: adhesion, biological effects of laser radiation, biomedical optical imaging, blood, blood flow measurement, blood vessels, cellular biophysics, coagulation, diseases, flow visualisation, laser applications in medicine, photothermal effects, shear flowOther keywords: in vivo measurement, blood flow, microscale stenosis model, laser photothermal blood coagulation, stenosed vessel, circulatory diseases, haemodynamics, extraembryonic vessels, chicken embryo, laser irradiation, blood vessel, red blood cells, blood coagulum, adherence, vessel wall, microparticle image velocimetry, shear rate, circulatory vascular diseasesInspec keywords: adhesion, biological effects of laser radiation, biomedical optical imaging, blood, blood flow measurement, blood vessels, cellular biophysics, coagulation, diseases, flow visualisation, laser applications in medicine, photothermal effects, shear flowOther keywords: in vivo measurement, blood flow, microscale stenosis model, laser photothermal blood coagulation, stenosed vessel, circulatory diseases, haemodynamics, extraembryonic vessels, chicken embryo, laser irradiation, blood vessel, red blood cells, blood coagulum, adherence, vessel wall, microparticle image velocimetry, shear rate, circulatory vascular diseases     

球囊扩张式血管支架介入对弯曲血管的生物力学损伤研究

构建了球囊扩张式血管支架介入系统的非线性有限元模型,考虑了血管斑块类型对其本构模型的影响,分析了A型与B型血管支架在血管狭窄率-24%、40%、50%,曲率半径-6 mm、10 mm、20 mm,狭窄血管的壁面应力分布规律,研究了血管支架构型、狭窄血管几何参数和血管生物力学损伤的关系。数值分析结果表明,血管壁面应力随着狭窄率的增加而显著升高,随着血管曲率半径的增加而下降相对平缓;但是,扩张加载阶段的血管壁面应力显著高于卸载阶段,易于引起血管斑块的脆性断裂引起血管生物力学损伤。由于A型血管支架相对于B型血管支架具有纵向柔顺性更优的联接筋构型,导致A型血管支架引起的血管壁面应力低于B型支架,因而降低了A型血管支架对于血管的生物力学损伤。     

Anti‐Atherogenic Effect of Stem Cell Nanovesicles Targeting Disturbed Flow Sites

Atherosclerosis development leads to irreversible cascades, highlighting the unmet need for improved methods of early diagnosis and prevention. Disturbed flow formation is one of the earliest atherogenic events, resulting in increased endothelial permeability and subsequent monocyte recruitment. Here, a mesenchymal stem cell (MSC)‐derived nanovesicle (NV) that can target disturbed flow sites with the peptide GSPREYTSYMPH (PREY) (PMSC‐NVs) is presented which is selected through phage display screening of a hundred million peptides. The PMSC‐NVs are effectively produced from human MSCs (hMSCs) using plasmid DNA designed to functionalize the cell membrane with PREY. The potent anti‐inflammatory and pro‐endothelial recovery effects are confirmed, similar to those of hMSCs, employing mouse and porcine partial carotid artery ligation models as well as a microfluidic disturbed flow model with human carotid artery‐derived endothelial cells. This nanoscale platform is expected to contribute to the development of new theragnostic strategies for preventing the progression of atherosclerosis.     

Biomechanical Strain Exacerbates Inflammation on a Progeria‐on‐a‐Chip Model

Organ‐on‐a‐chip platforms seek to recapitulate the complex microenvironment of human organs using miniaturized microfluidic devices. Besides modeling healthy organs, these devices have been used to model diseases, yielding new insights into pathophysiology. Hutchinson‐Gilford progeria syndrome (HGPS) is a premature aging disease showing accelerated vascular aging, leading to the death of patients due to cardiovascular diseases. HGPS targets primarily vascular cells, which reside in mechanically active tissues. Here, a progeria‐on‐a‐chip model is developed and the effects of biomechanical strain are examined in the context of vascular aging and disease. Physiological strain induces a contractile phenotype in primary smooth muscle cells (SMCs), while a pathological strain induces a hypertensive phenotype similar to that of angiotensin II treatment. Interestingly, SMCs derived from human induced pluripotent stem cells of HGPS donors (HGPS iPS‐SMCs), but not from healthy donors, show an exacerbated inflammatory response to strain. In particular, increased levels of inflammation markers as well as DNA damage are observed. Pharmacological intervention reverses the strain‐induced damage by shifting gene expression profile away from inflammation. The progeria‐on‐a‐chip is a relevant platform to study biomechanics in vascular biology, particularly in the setting of vascular disease and aging, while simultaneously facilitating the discovery of new drugs and/or therapeutic targets.     

Integrating Flexible Electrochemical Sensor into Microfluidic Chip for Simulating and Monitoring Vascular Mechanotransduction

As an interface between the blood flow and vessel wall, endothelial cells (ECs) are exposed to hemodynamic forces, and the biochemical molecules released from ECs–blood flow interaction are important determinants of vascular homeostasis. Versatile microfluidic chips have been designed to simulate the biological and physiological parameters of the human vascular system, but in situ and real‐time monitoring of the mechanical force–triggered signals during vascular mechanotransduction still remains a significant challenge. Here, such challenge is fulfilled for the first time, by preparation of a flexible and stretchable electrochemical sensor and its incorporation into a microfluidic vascular chip. This allows simulating of in vivo physiological and biomechanical parameters of blood vessels, and simultaneously monitoring the mechanically induced biochemical signals in real time. Specifically, the cyclic circumferential stretch that is actually exerted on endothelium but is hard to reproduce in vitro is successfully recapitulated, and nitric oxide signals under normal blood pressure, as well as reactive oxygen species signals under hypertensive states, are well documented. Here, the first integration of a flexible electrochemical sensor into a microfluidic chip is reported, therefore paving a way to evaluate in vitro organs by built‐in flexible sensors.     

Use of the subcutaneous venous network of the forearm to create an arteriovenous fistula

The reconstruction of vascular access in patients with kidney allograft failure is a challenging problem. A case of a 62‐year‐old man with transplanted kidney insufficiency is described. The patient was initially dialyzed with a wrist radial‐cephalic arteriovenous fistula. In the post‐transplantation period, the enormously dilated venous part of the anastomosis was ligated and the part of the vein suspected of being the source of bacteremia was excised. The man was referred to our department due to kidney allograft failure for vascular access creation. During preoperative assessment, we unexpectedly found a soft thrill on the forearm. Doppler ultrasound confirmed fistula patency, although the blood supply was not sufficient to perform dialysis. Angiography showed the blood flow from the radial artery to the cephalic vein, through a complicated vessel system consisting of inter alia a dilated vein of the subcutaneous venous network. We successfully used this vein as the vascular access outflow for fistula recreation. In conclusion, making use of veins of the subcutaneous venous network of the forearm for creation of a native fistula should be considered in selected cases.     

Effect of intermittent compression of upper arm veins on forearm vessels in patients with end-stage renal disease

Native arteriovenous fistula is the best vascular access for chronic hemodialysis. Primary and long-term success depends, in part, on the state of arteries and veins at the time of the operation. The aim of our study was to investigate the effects of intermittent compression of upper arm veins on forearm vessels in patients with terminal renal disease. The study group was composed of 16 chronic hemodialysis patients who performed daily intermittent compression of the upper arm without vascular access by elastic band (Eschmarch). Ten chronic hemodialysis patients were included in the control group, which performed no specific activity. Forearm measurements were obtained at the beginning of the study and 4 and 8 weeks later during the course of intermittent compression of the upper arm veins. The forearm circumference and maximal handgrip strength were measured. The artery measures, including endothelium-dependent vasodilatation and forearm vein variables, were obtained by ultrasonography measurements. The forearm circumference, maximal handgrip strength, and artery variables, including endothelium-dependent vasodilatation, remained unchanged. The basal venous diameters (2.29 +/- 0.19 mm at the beginning, 2.46 +/- 0.19 mm after 4 weeks, and 2.53 +/- 0.18 mm after 8 weeks) were significantly increased in the study group. The distensibility of veins was preserved in the study group. There were no significant changes in the control group. Our study demonstrated that daily intermittent compression of the upper arm veins increases the forearm vein diameter and preserves the distensibility of veins in patients with end-stage renal failure.     

The flow field near a venous needle in hemodialysis: A computational study

The vascular access used in hemodialysis can suffer from numerous complications, which may lead to failure of the access, patient morbidity, and significant costs. The flow field in the region of the venous needle may be a source of damaging hemodynamics and hence adverse effects on the fistula. In this study, the venous needle flow has been considered, using three‐dimensional computational methods. Four scenarios where the venous needle flow could potentially influence dialysis treatment outcome were identified and examined: Variation of the needle placement angle (10°, 20°, 30°), variation of the blood flow rate settings (200, 300, 400 mL/min), variation of the needle depth (top, middle, bottom), and the inclusion of a back eye in the needle design. The presence of the needle has significant effect on the flow field, with different scenarios having varying influence. In general, wall shear stresses were elevated above normal physiological values, and increased presence of areas of low velocity and recirculation—indicating increased likelihood of intimal hyperplasia development—were found. Computational results showed that the presence of the venous needle in a hemodialysis fistula leads to abnormal and potentially damaging flow conditions and that optimization of needle parameters could aid in the reduction of vascular access complications. Results indicate shallow needle angles and lower blood flow rates may minimize vessel damage.     

Optimum pulse duration and radiant exposure for vascular laser therapy of dark port-wine skin: a theoretical study

Laser therapy for cutaneous hypervascular malformations such as port-wine stain birthmarks is currently not feasible for dark-skinned individuals. We study the effects of pulse duration, radiant exposure, and cryogen spray cooling (CSC) on the thermal response of skin, using a Monte Carlo based optical-thermal model. Thermal injury to the epidermis decreases with increasing pulse duration during irradiation at a constant radiant exposure; however, maintaining vascular injury requires that the radiant exposure also increase. At short pulse durations, only a minimal increase in radiant exposure is necessary for a therapeutic effect to be achieved because thermal diffusion from the vessels is minimal. However, at longer pulse durations the radiant exposure must be greatly increased. There exists an optimum pulse duration at which minimal damage to the epidermis and significant injury within the targeted vasculature occur. For example, the model predicts optimum pulse durations of approximately 1.5, 6, and 20 ms for vessel diameters of 40, 80, and 120 microm, respectively. Optimization of laser pulse duration and radiant exposure in combination with CSC may offer a means to treat cutaneous lesions in dark-skinned individuals.     

Multicellular Vascularized Engineered Tissues through User‐Programmable Biomaterial Photodegradation

A photodegradable material‐based approach to generate endothelialized 3D vascular networks within cell‐laden hydrogel biomaterials is introduced. Exploiting multiphoton lithography, microchannel networks spanning nearly all size scales of native human vasculature are readily generated with unprecedented user‐defined 4D control. Intraluminal channel architectures of synthetic vessels are fully customizable, providing new opportunities for next‐generation microfluidics and directed cell function.