Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel‐like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel‐like scaffolds and endothelial cells seeded in their lumen form native‐like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites the bioprinted vasculature and endothelium to cooperatively create vessels, enabling tissue perfusion through the scaffold lumen. Using a cuffing microsurgery approach, the engineered tissue is directly anastomosed with a rat femoral artery, promoting a rich host vasculature within the implanted tissue. After two weeks in vivo, contrast microcomputer tomography imaging and lectin perfusion of explanted engineered tissues verify the host ingrowth vasculature's functionality. Furthermore, the hierarchical vessel network (VesselNet) supports in vitro functionality of cardiomyocytes. Finally, the proposed approach is expanded to mimic complex structures with native‐like millimetric vessels. This work presents a novel strategy aiming to create fully‐engineered patient‐specific thick tissue flaps.

Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making. In a human study involving 32 patients, we introduced the clinical application of a miniaturized endovascular neuro optical coherence tomography ( n OCT) imaging probe. This technology was designed to navigate the tortuous paths of the cerebrovascular circulation and to offer high-resolution imaging in situ. The n OCT probe is compatible with standard neurovascular microcatheters, integrating with the procedural workflow used in clinical routine. Equipped with a miniaturized optical fiber and a distal lens, the probe illuminates the tissue and collects the backscattered, near-infrared light. While rotating the fiber and the lens at high speed, the probe is rapidly retracted, creating a spiral-shaped light pattern to comprehensively capture the arterial wall and implanted devices. Using n OCT, we demonstrated volumetric microscopy of cerebral arteries in patients undergoing endovascular procedures. We imaged the anterior and posterior circulation of the brain, including distal segments of the internal carotid and middle-cerebral arteries, as well as the vertebral, basilar, and posterior cerebral arteries. We captured a broad spectrum of neurovascular pathologies, such as brain aneurysms, ischemic stroke, arterial stenoses, dissections, and intracranial atherosclerotic disease. n OCT offered artifact-free, high-resolution visualizations of intracranial artery pathology and neurovascular devices.

Vascularization of 3D engineered tissues poses a great challenge in the field of tissue engineering. One promising approach for vascularizing engineered tissue is cocultivation with endothelial cells (ECs), which spontaneously self-assemble into a natural capillary network in the presence of supportive cells. However, the ECs do not self-assemble according to physiological hierarchy which is required to support blood supply. This work describes the design and fabrication of an AngioTube, a biodegradable engineered macro-vessel surrounded by cylindrical micro-channel array, which is designed to support physiological flow distribution and enable the integration with living capillaries. The well-defined geometry of the engineered micro-channels guides endothelial cells to form patent micro-vessels which sprouted in accordance with the channel orientation. Three different in-vitro models were used to demonstrate anastomosis of these engineered micro-vessels with self-assembled vascular networks. Finally, in-vivo functionality was demonstrated by direct anastomosis with the femoral artery in a rat hindlimb model. This unique approach proposes a new micro-fabrication strategy which introduces uncompromised micro-fluidic device geometrical accuracy at the tissue-scale level. STATEMENT OF SIGNIFICANCE: This study proposes a micro-fabrication strategy suitable for processing real-scale cylindrical implants with very high accuracy, which will enable translation of the high-resolution geometry of micro-fluidic devices to clinically relevant implants containing functional multi-scale vascular networks. Moreover, this approach promises to advance the field of tissue engineering by opening new opportunities to explore the impact of well controlled and uncompromised 3D micro-geometry on cellular behavior.

Background The micro-architectonics of the subarachnoid space (SAS) remain partially understood and largely ignored, likely the result of the inability to image these structures in vivo. We explored transvascular imaging with high-frequency optical coherence tomography (HF-OCT) to interrogate the SAS. Methods In vivo HF-OCT was performed in 10 dogs in both the posterior and anterior cerebral circulations. The conduit vessels used were the basilar, anterior spinal, and middle and anterior cerebral arteries through which the perivascular SAS was imaged. The HF-OCT imaging probe was introduced via a microcatheter and images were acquired using a contrast injection (3.5 mL/s) for blood clearance. Segmentation and three-dimensional rendering of HF-OCT images were performed to study the different configurations and porosity of the subarachnoid trabeculae (SAT) as a function of location. Results Of 13 acquisitions, three were excluded due to suboptimal image quality. Analysis of 15 locations from seven animals was performed showing six distinct configurations of arachnoid structures in the posterior circulation and middle cerebral artery, ranging from minimal presence of SAT to dense networks and membranes. Different locations showed predilection for specific arachnoid morphologies. At the basilar bifurcation, a thick, fenestrated membrane had a unique morphology. SAT average thickness was 100 µm and did not vary significantly based on location. Similarly, the porosity of the SAT averaged 91% and showed low variability. Conclusion We have demonstrated the feasibility to image the structures of the SAS with transvascular HF-OCT. Future studies are planned to further map the SAT to increase our understanding of their function and possible impact on neurovascular pathologies.

Background Flow diversion has become a standard treatment for cerebral aneurysms. However, major drawbacks include the need for dual antiplatelet therapy after implant and delayed complete occlusion of the aneurysm, which occurs when new tissue growth excludes the aneurysm from the parent artery. Biomimetic surface modifications such as the phosphorylcholine polymer (Shield surface modification) represent major advances in reducing thrombogenicity of these devices. However, in vitro studies have raised concerns that this modification may also delay endothelialization of flow diverters. Methods Bare metal Pipeline, Pipeline Shield, and Vantage with Shield devices were implanted in the common carotid arteries (CCAs) of 10 rabbits (two in the left CCA, one in the right CCA). Following implant and at 5, 10, 15, and 30 days, the devices were imaged with high-frequency optical coherence tomography and conventional angiography to evaluate tissue growth. At 30 days the devices were explanted and their endothelial growth was assessed with scanning electron microscopy (SEM) at five locations along their length using a semi-quantitative score. Results The average tissue growth thickness (ATGT) was not different between the three devices. Neointima was apparent at 5 days and all devices demonstrated similar ATGT at each time point. On SEM, no difference was found in the endothelium scores between the device types. Conclusion In vivo, neither the Shield surface modification nor the device design (Vantage) altered the longitudinal healing of the flow diverter.