Tissue Vessels Research Articles

1H26 繊維状三次元担体を用いた血管組織の生体外構築

1H26 繊維状三次元担体を用いた血管組織の生体外構築

In vivo cardiovascular magnetic resonance of 2D vessel wall diffusion anisotropy in carotid arteries

BackgroundDiffusion weighted (DW) cardiovascular magnetic resonance (CMR) has shown great potential to discriminate between healthy and diseased vessel tissue by evaluating the apparent diffusion coefficient (ADC) along the arterial axis. Recently, ex vivo studies on porcine arteries utilizing diffusion tensor imaging (DTI) revealed a circumferential fiber orientation rather than an organization in axial direction, suggesting dominant diffusion perpendicular to the slice direction. In the present study, we propose a method to access tangential and radial diffusion of carotids in vivo by utilizing a pulse sequence that enables high resolution DW imaging in combination with a two-dimensional (2D) diffusion gradient direction sampling scheme perpendicular to the longitudinal axis of the artery.MethodsHigh resolution DTI of 12 healthy male volunteers (age: 25–60 years) was performed on one selected axial slice using a read-out segmented EPI (rs-EPI) sequence on a 3T MR scanner.ResultsIt was found consistently for all 12 volunteers, that the tangential component as the principle direction of diffusion. Mean vessel wall fractional anisotropy (FA) values ranged from 0.7 for the youngest to 0.56 for the oldest participant. Linear regression analysis between the FA values and volunteers age revealed a highly significant (P < 0.01) linear relationship with an adjusted R2 of 0.52. In addition, a linear trend (P < 0.1) could be observed between radial diffusivity (RD) and age.ConclusionThese results point to FA being a sensitive parameter able to capture changes in the vascular architecture with age. In detail, the data demonstrate a decrease in FA with advancing age indicating possible alterations of tissue microstructural integrity. Moreover, analyzing 2D diffusion tensor directions is sufficient and applicable in a clinical setup concerning the overall scan time.

Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review

Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept "bio-adaption" between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed.

Vascularization after treatment of gingival recession defects with platelet-rich fibrin or connective tissue graft.

The aim of this study was to evaluate histologically the following treatment of bilateral localized gingival recessions with coronally advanced flap (CAF) combined with platelet-rich fibrin (PRF) or subepithelial connective tissue graft (SCTG). Tissue samples were harvested from 14 subjects either 1 or 6months after the surgeries. The 2-mm punch biopsies were obtained from the mid-portion of the grafted sites. Neutral buffered formalin fixed, paraffin-embedded 5-μm thick tissue sections were stained with hematoxylin eosin and Masson's trichrome in order to analyze the collagen framework, epithelium thickness and rete-peg length. Multiple sequential sections were cut from paraffin-embedded blocks of tissue and immunohistochemically prepared for detection of vascular endothelial growth factor, CD31 and CD34, for the assessment of vascularization. Rete peg formation was significantly increased in the sites treated with PRF compared to the SCTG group after 6months (p < 0.05). On the contrary, the number of vessels was increased in the SCTG group compared to the PRF group after 6months (p < 0.05). No statistically significant differences were observed in the collagen density. Staining intensity of CD31 increased in submucosal area of PRF group than SCTG group after 1month. Higher staining intensity of CD34 was observed in the submucosal area of PRF group compared with SCTG group after 6months. The results of the present study suggest that in histological evaluation because of its biological compounds, PRF results earlier vessel formation and tissue maturation compared to connective tissue graft. PRF regulated the vascular response associated with an earlier wound healing.

Platelet Activation Gradients During Thrombus Formation

The hemostatic response requires the tightly regulated interaction of the coagulation system, platelets, other blood cells and components of the vessel wall at a site of vascular injury. The dysregulation of this response may result in excessive bleeding if the response is impaired, and pathologic thrombosis with vessel occlusion and tissue ischemia if the response is overly robust. Extensive studies over the past decades have sought to unravel the regulatory mechanisms that coordinate the multiple biochemical and cellular responses in time and space to ensure that an optimal response to vascular damage is achieved. We and others have observed that platelet activation at a site of injury in vivo is heterogeneous, with a gradient of platelet activation extending from the site of injury. Platelets immediately adjacent to the injured vessel wall are densely packed and fully activated forming a stably adherent core region. This stable core is overlaid by a shell of less activated platelets that are more loosely packed. Genetic and pharmacologic studies have shown that the formation of these regions is dependent on partially overlapping gradients of distinct platelet agonists, with ADP serving as a mediator of platelet recruitment and retention in the shell region, and thrombin necessary for full platelet activation in the core region. The distribution of platelet agonists and other plasma solutes in time and space is in turn determined in part by their transport in the plasma microenvironments that evolve as platelets accumulate. Platelet mass consolidation and the subsequent narrowing of the gaps between platelets are important mechanisms by which plasma solutes are retained within the platelet mass to promote platelet activation. Consolidation also regulates the escape of plasma and platelet-derived bioactive molecules into the extravascular space. These studies and others examining how cellular, biochemical and physical factors are integrated to shape the optimal response to vascular injury in vivo will be discussed. Disclosures No relevant conflicts of interest to declare.

Carotid Endarterectomy Surgical Simulation Model Using a Bovine Placenta Vessel.

Carotid endarterectomy (CEA) is a common, well-developed surgical procedure. Although surgical simulation is gaining in importance for residency training, CEA practice opportunities for surgical residents are limited. To describe a new haptic CEA model. Six bovine placentas were used to create the model. Each placenta provided about 6 large arterial and venous bifurcations. In total, 36 large-vessel bifurcations were dissected and prepared for the CEA simulation. Bovine placenta vessels were arranged to simulate the common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA). The diameters and wall thicknesses were measured and compared with human CCA, ICA, and ECA parameters. All bovine placentas provided vessels suitable for modeling carotid artery bifurcations and CEA training. Mean ± SD diameters of simulated CCAs, ECAs, and ICAs were 11.2 ± 1.8, 4.3 ± 0.5, and 9.8 ± 3.0 mm, respectively, from nondilated veins and 8.7 ± 1.4, 4.4 ± 1.3, and 7.2 ± 1.7 mm, respectively, from nondilated arteries. Mean vessel wall thicknesses were 2.0 ± 0.6 mm for arteries and 1.4 ± 0.5 mm for veins. Placental vessel tissue had dimensions and handling characteristics similar to those of human carotid arteries. The CEA procedure and its subtasks, including vessel-tissue preparation and surgical skills performance, could be reproduced with high fidelity. A bovine placenta training model for CEA is inexpensive and readily available and closely resembles human carotid arteries. The model can provide a convenient and valuable simulation and practice addition for vascular surgery training.

Preparation of decellularized vascular matrix by co-crosslinking of procyanidins and glutaraldehyde.

Vascular extracellular matrices (vECMs) have shown potential for small-diameter blood vessel tissue engineering applications. However, problems such as chemical instability and easy calcification are still remained. Chemical crosslinking using crosslinkers such as glutaraldehyde (GA) can improve mechanical properties and proteolysis resistance of vECMs, but leads to calcification and cytotoxicity. Procyanidins (PC) can crosslink ECMs with anti-calcification property and cytocompatibility, but the mechanical properties and chemical stability are unsatisfactory. A novel co-crosslinking technique using PC and GA was developed, which combines the advantages of both PC and GA for enhancing mechanical properties and stability of vECMs with reduced calcification and cytotoxicity. Fresh carotid were decellularized and then crosslinked by PC and subsequent GA for 6 h respectively. The mechanical properties, dynamic release of PC, enzymatic degradation, calcification and cytotoxicity of crosslinked samples were evaluated. The co-crosslinked vECMs showed enhanced tensile strength, chemical and biological stability, comparable anti-calcification property as compared to pure PC-crosslinked samples. Cytotoxicity assay showed that the co-crosslinked vECMs were cytocompatible for supporting the adhesion and proliferation of HUVECs. Co-crosslinking with PC and GA might be a useful method for preparation of vECM scaffolds with potential applications in small-diameter blood vessel tissue engineering.

Abstract P120: Improving the Angiogenic Abilities of Mobilized Peripheral Blood Stem Cells Achieved by Priming with Activated Platelet Supernatant for Regenerative Cell Therapy

Platelets play a critical role in hemostasis and also have ability to promote angiogenesis and tissue repair by secreting of numerous cytokine and making angiogenic condition. We investigated whether autologous ‘activated platelet supernatant (APS)’ has effect on enhancing pro-angiogenic potential of peripheral blood stem cells (PBSC) for stem cell-based therapy for ischemic diseases. Granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (mobPBSC) were isolated from healthy volunteers, while APS was collected from platelet rich plasma by thrombin activation. mobPBSCs were primed with APS (APS primed mobPBSCs) for 6 hours, and APS primed mobPBSCs characterized their angiogenic ability. For the safety analysis, we estimated the thrombogenicity of platelets in whole blood mixed with APS primed mobPBSCs by expression of glycoprotein IIb and IIIa on platelets. APS had a higher level of various cytokines, such as IL8, IL17, PDGF and VEGF than naïve platelet supernatants. And APS primed mobPBSCs had more expression of angiogenic factors, surface markers (i.e. CD34, CD31, and CXCR4) and integrins (integrin α5, β1 and β2) than Veh primed and Pre primed mobPBSC. Also APS primed mobPBSCs were polarized toward CD14++/CD16+ pro-angiogenic monocytes. And result in adhesion to endothelial cells and fibronectin which represents cell to cell and cell to extracellular matrix adhesion, respectively. The culture supernatant of APS-primed mobPBSCs contained high levels of IL8, IL10, IL17 and TNFα, and augmented proliferation and capillary network formation of HUVEC. In-vivo transplantation of APS-primed mobPBSC into athymic mice ischemic hindlimbs and Matrigel plugs elicited vessel differentiation and tissue repair. In thrombogenicity test, platelet activity increased after mixing whole blood with mobPBSC regardless of the priming agent. However, this was reduced by pretreatment of aspirin, which is an antiplatelet agent prescribed to patients with ischemic diseases. Our data demonstrate that mobPBSCs primed with APS improve angiogenic potential, and that can be adjunctive strategy to enhance the efficiency of stem cell therapy for ischemic diseases.

Method for estimating the temperature distribution associated with the vessel cooling effect in radio frequency ablation.

Recently, radio frequency ablation (RFA) has become one of the most popular thermal treatments for liver cancer. RFA is minimally invasive and effective in inducing tumor coagulation, however, because use the procedure depends on the experience of the physician, consistent accuracy cannot be guaranteed. In particular, when the tumor is close to a large vessel, a suboptimal ablation margin can result in tumor recurrence. To improve the accuracy of RFA treatment, we have developed an RFA supporting system, which was constructed by using finite element method and operated by means of a model-based control method. In this study, we focused on the cooling effect of flow volume inside a large vessel during RFA, and analyzed heat transfer between the large vessel and liver tissue using a model. We derived the heat transfer parameter (the Nusselt number (Nu)) between the large vessel and liver tissue during RFA by using a finite-element method (FEM). When the Nu for FEM analysis had a value of 3, the FEM analysis model was representative of the actual ablation objective, and the maximum error between FEM analysis and the measurement results was within 2.0[°C]. Thus, it was suggested that the Nu was effective for FEM analysis regarding heat transfer between a large vessel and tissue. However, according to the differences between the results of FEM analysis and measurements concerning the three livers, the heat transfer volume was determined by the Nu, which is different individually in common with other thermal properties. In conclusion, it is necessary to consider the individual differences in the heat transfer volume parameter for FEM analysis.

Abstract 4536: Biomimetic carriers modulate tumor vascular barrier function

Abstract Introduction We showed that nanoporous silicon (NPS) particles coated with leukocyte cellular membranes -Leukolike Vectors (LLV) - possess cell-like properties. These biomimetic carriers can escape macrophage uptake, delay sequestration by the reticulo-endothelial system, target tumor inflamed vasculature and accumulate within the cancer parenchyma. We characterized the content and function of the leukocyte's proteins transferred onto the LLV coating and evaluated their interaction with inflamed cancer vasculature. Experimental Procedures The leukocyte membrane coating was analyzed with several biochemistry techniques. In vitro experiments were performed using reconstructed inflamed endothelia. Flow chamber systems were used to simulate vessel flow dynamics and study LLV docking, firm adhesion and transcytosis. In vivo experiments were performed with Intra Vital Microscopy (IVM) to image in real time LLV behavior in BALB/c mice carrying syngeneic breast cancers. Results LLV were studied using dynamic light scattering and scanning electron microscopy to characterize particles size (1 μm), pore sizes (60 nm) and surface properties (positive charge and uniform coating). Biochemical analyses revealed that we successfully transferred on the surface of the LLV critical protein among which LFA-1, MAC1, and CD45. Upon interaction of the LLV with inflamed endothelia we found that VE-cadherin expression was substantially reduced. We also described the differential process of cell internalization and showed that LLV escaped the endo-lysosomal compartment during intracellular trafficking. IVM showed delayed sequestration by spleen and liver macrophages, increased circulation half-life and increased targeting of tumor associated inflamed vasculature. To further demonstrate the ability of our biomimetic carrier to affect the biology of tumor endothelia, we evaluated the extravasation of an intravascular 70 kDa FITC dextran reporter. We measured the increase in vessel permeability and tissue diffusion over time and confirmed that LLV were able to favor the extravasation of the reporter molecule in the cancer parenchyma. Conclusion Our work showed for the first time that is possible to transfer biologically active leukocyte membrane proteins onto synthetic particles. Our biomimetic carriers retain favorable cell-like functions that can enhance the kinetics of oncotransport by decreasing endothelial cellular junctions and increasing diffusion of a therapeutic payload within the tumor tissue. We envision that biomimetic drug delivery systems derived from the infiltrating immune cells of a cancer patient could represent the next generation of personalized treatments. Note: This abstract was not presented at the meeting. Citation Format: Alessandro Parodi, Roberto Palomba, Michael Evangelopoulos, Claudia Corbo, Ennio Tasciotti. Biomimetic carriers modulate tumor vascular barrier function. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4536. doi:10.1158/1538-7445.AM2015-4536

Influence of Rotation Rate of Collecting Roller on the Mechanical Property of PCL/SF Tubular Scaffolds

The composite tubular scaffolds with highly oriented nanofibers used for vascular repair could improve the biomechanical properties of tubular scaffolds, satisfying the biomechanical requirement for the change of blood pressure and conducing to cell adhesion, migration and proliferation. The tubular scaffolds from poly(ε-caprolactone)(PCL) and silk fibroin (SF) composite nanofibers were successfully fabricated through electrospinning using cylindrical roller with an outer diameter (OD) of 3.0 mm. The influences of the collecting rotatation speeds on electrospun PCL/SF nanofibers orientation and radial/axial mechanical properties of the scaffolds were investigated. The results revealed that the electrospun PCL/SF tubular scaffolds fabricated at 1500 and 2000 r/min (linear velocity of 2.1, 2.8 m/s, respectively) possessed good arrangement around the circumferential direction of roller and sufficient radial strength and suture strength. The electrospun PCL/SF tubular scaffolds with circumferential-direction structure as a new vascular graft may be useful in vessel tissue engineering.

Cerebrovascular MRI: a review of state-of-the-art approaches, methods and techniques.

Cerebrovascular imaging is of great interest in the understanding of neurological disease. MRI is a non-invasive technology that can visualize and provide information on: (i) the structure of major blood vessels; (ii) the blood flow velocity in these vessels; and (iii) the microcirculation, including the assessment of brain perfusion. Although other medical imaging modalities can also interrogate the cerebrovascular system, MR provides a comprehensive assessment, as it can acquire many different structural and functional image contrasts whilst maintaining a high level of patient comfort and acceptance. The extent of examination is limited only by the practicalities of patient tolerance or clinical scheduling limitations. Currently, MRI methods can provide a range of metrics related to the cerebral vasculature, including: (i) major vessel anatomy via time-of-flight and contrast-enhanced imaging; (ii) blood flow velocity via phase contrast imaging; (iii) major vessel anatomy and tissue perfusion via arterial spin labeling and dynamic bolus passage approaches; and (iv) venography via susceptibility-based imaging. When designing an MRI protocol for patients with suspected cerebral vascular abnormalities, it is appropriate to have a complete understanding of when to use each of the available techniques in the 'MR angiography toolkit'. In this review article, we: (i) overview the relevant anatomy, common pathologies and alternative imaging modalities; (ii) describe the physical principles and implementations of the above listed methods; (iii) provide guidance on the selection of acquisition parameters; and (iv) describe the existing and potential applications of MRI to the cerebral vasculature and diseases. The focus of this review is on obtaining an understanding through the application of advanced MRI methodology of both normal and abnormal blood flow in the cerebrovascular arteries, capillaries and veins.

Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma.

2025 Background: Tivozanib, an oral, pure VEGFR tyrosine kinase inhibitor is an anti-angiogenesis drug which aims to modulate the tumor blood supply. This phase II study was designed to test the effectiveness of tivozanib on tumor vasculature in patients with recurrent GBM. Methods: Ten adult patients with recurrent GBM, median age of 62 (range 51-73), were enrolled on a Simon 2-stage design study and treated with tivozanib 1.5mg daily, 3 weeks on/1 week off in 28 day cycles. Brain MRI was done at baseline and after each cycle. The enhancing tumor and surrounding area of abnormal FLAIR hyperintensity were outlined and median tumor cerebral blood flow (CBF) and cerebral blood volume (CBV) values were derived from dynamic susceptibility contrast MRI to assess the performance of tivozanib. Vessel architectural imaging (VAI) was used to measure tumor vessel calibers and relative oxygen saturation. A t-test was used to compare baseline MRI parameters to the pre-cycle 3 visit. A univariate Cox model was used to test the association of each MRI parameter with time to progression. Results: Best MacDonald criteria responses were: CR (1), PR (1), SD (4), PD (4) and the median duration of response was only 3.6 mo (1.7-3.8mo) so the study was stopped per planned stopping rule. One patient was taken off study for unacceptable skin toxicity and nine patients for progressive disease. Given the dropout rate, only data up to cycle 3 was included in this analysis. There was no statistically significant change in enhancing tumor volume (p = 0.70), FLAIR volume (p = 0.31), or median CBV (p = 0.13) or median CBF (p = 0.54) within the enhancing tumor. Within the FLAIR hyperintensity, median CBV (p = 0.12) and median CBF (p = 0.41) also did not change significantly. No parameter was associated with time to tumor progression. VAI showed no change in vessel calibers or tissue oxygenation. Conclusions: Tivozanib was well tolerated but most patients progressed rapidly. The majority of patients had no significant change in tumor enhancement and perfusion imaging demonstrated insignificant changes in tumor and peritumoral blood volume, flow, vessel caliber, and oxygenation, suggesting that this anti-angiogenic agent had limited impact on brain tumor vasculature. Clinical trial information: NCT01846871.

Palmitate-induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis.

Obesity is associated with inflammation and immune cell recruitment to adipose tissue, muscle and intima of atherosclerotic blood vessels. Obesity and hyperlipidemia are also associated with tissue insulin resistance and can compromise insulin delivery to muscle. The muscle/fat microvascular endothelium mediates insulin delivery and facilitates monocyte transmigration, yet its contribution to the consequences of hyperlipidemia is poorly understood. Using primary endothelial cells from human adipose tissue microvasculature (HAMEC), we investigated the effects of physiological levels of fatty acids on endothelial inflammation and function. Expression of cytokines and adhesion molecules was measured by RT-qPCR. Signaling pathways were evaluated by pharmacological manipulation and immunoblotting. Surface expression of adhesion molecules was determined by immunohistochemistry. THP1 monocyte interaction with HAMEC was measured by cell adhesion and migration across transwells. Insulin transcytosis was measured by total internal reflection fluorescence microscopy. Palmitate, but not palmitoleate, elevated the expression of IL-6, IL-8, TLR2 (Toll-like receptor 2), and intercellular adhesion molecule 1 (ICAM-1). HAMEC had markedly low fatty acid uptake and oxidation, and CD36 inhibition did not reverse the palmitate-induced expression of adhesion molecules, suggesting that inflammation did not arise from palmitate uptake/metabolism. Instead, inhibition of TLR4 to NF-κB signaling blunted palmitate-induced ICAM-1 expression. Importantly, palmitate-induced surface expression of ICAM-1 promoted monocyte binding and transmigration. Conversely, palmitate reduced insulin transcytosis, an effect reversed by TLR4 inhibition. In summary, palmitate activates inflammatory pathways in primary microvascular endothelial cells, impairing insulin transport and increasing monocyte transmigration. This behavior may contribute in vivo to reduced tissue insulin action and enhanced tissue infiltration by immune cells.

Cells and stimuli in small-caliber blood vessel tissue engineering.

The absence of successful solutions in treatments of small-caliber vessel diseases led to the Vascular Tissue Engineering approach to develop functional nonimmunogenic tissue engineered blood vessels. In this context, the choice of cells to be seeded and the microenvironment conditioning are pivotal. Biochemical and biomechanical stimuli seem to activate physiological regulatory pathways that induce the production of molecules and proteins stimulating stem cell differentiation toward vascular lineage and reproducing natural cross-talks among vascular cells to improve the maturation of tissue engineered blood vessels. Thus, this review focuses on (1) available cell sources, and (2) biochemical and biomechanical stimuli, with the final aim to obtain the long-term stability of the endothelium and mechanical properties suitable for withstanding physiological load.

Assessment of vessel permeability by combining dynamic contrast-enhanced and arterial spin labeling MRI.

The forward volumetric transfer constant (K(trans)), a physiological parameter extracted from dynamic contrast-enhanced (DCE) MRI, is weighted by vessel permeability and tissue blood flow. The permeability × surface area product per unit mass of tissue (PS) in brain tumors was estimated in this study by combining the blood flow obtained through pseudo-continuous arterial spin labeling (PCASL) and K(trans) obtained through DCE MRI. An analytical analysis and a numerical simulation were conducted to understand how errors in the flow and K(trans) estimates would propagate to the resulting PS. Fourteen pediatric patients with brain tumors were scanned on a clinical 3-T MRI scanner. PCASL perfusion imaging was performed using a three-dimensional (3D) fast-spin-echo readout module to determine blood flow. DCE imaging was performed using a 3D spoiled gradient-echo sequence, and the K(trans) map was obtained with the extended Tofts model. The numerical analysis demonstrated that the uncertainty of PS was predominantly dependent on that of K(trans) and was relatively insensitive to the flow. The average PS values of the whole tumors ranged from 0.006 to 0.217 min(-1), with a mean of 0.050 min(-1) among the patients. The mean K(trans) value was 18% lower than the PS value, with a maximum discrepancy of 25%. When the parametric maps were compared on a voxel-by-voxel basis, the discrepancies between PS and K(trans) appeared to be heterogeneous within the tumors. The PS values could be more than two-fold higher than the K(trans) values for voxels with high K(trans) levels. This study proposes a method that is easy to implement in clinical practice and has the potential to improve the quantification of the microvascular properties of brain tumors.

Understanding nonlinear vibration behaviours in high-power ultrasonic surgical devices.

Ultrasonic surgical devices are increasingly used in oral, craniofacial and maxillofacial surgery to cut mineralized tissue, offering the surgeon high accuracy with minimal risk to nerve and vessel tissue. Power ultrasonic devices operate in resonance, requiring their length to be a half-wavelength or multiple-half-wavelength. For bone surgery, devices based on a half-wavelength have seen considerable success, but longer multiple-half-wavelength endoscopic devices have recently been proposed to widen the range of surgeries. To provide context for these developments, some examples of surgical procedures and the associated designs of ultrasonic cutting tips are presented. However, multiple-half-wavelength components, typical of endoscopic devices, have greater potential to exhibit nonlinear dynamic behaviours that have a highly detrimental effect on device performance. Through experimental characterization of the dynamic behaviour of endoscopic devices, it is demonstrated how geometrical features influence nonlinear dynamic responses. Period doubling, a known route to chaotic behaviour, is shown to be significantly influenced by the cutting tip shape, whereas the cutting tip has only a limited effect on Duffing-like responses, particularly the shape of the hysteresis curve, which is important for device stability. These findings underpin design, aiming to pave the way for a new generation of ultrasonic endoscopic surgical devices.

Mo1891 KLF2 Function on the Pathological Angiogenesis in Patients of Cirrhosis-Induced Portal Hypertension

Background & Aims Intrahepatic and splanchnic angiogenesis plays an important role in Portal Hypertension (PHT) caused by cirrhosis. Krupple-like factor 2 (KLF2), a critical angiogenic protective factor, can maintain endothelial cellular phenotype by negatively regulating angiogenesis. Our research is to study whether KLF2 play a role in cirrhosisinduced PHT and its possible mechanism. Methods Human serum samples were collected from 41 PHT patients and 20 healthy subjects, and portal vessel tissue were obtained from 6 PHT patients and 6 cholecystitis controls during their surgeries. Rat models of portal vein ligation (PVL) and CCL4 were also used for our study. The expression of KLF2 and relevant angiogenic factors such asHIF-1α and VEGFwere evaluated. Additionally, human endothelial cells were used for vitro study. Lentivirus was transfected to overexpress KLF2. Tube formation and activation of cells were examined while KLF2 target protein expression were determined. Results We observed a remarkable upregluation of KLF2 in portal vein of PHT patients and angiogenic duodenum of PVL rats compared with controls, accompanied by a significant increasement of some relevant angiogenic factors such as VEGF and HIF-1α in PHT human and rat model. In addition, our vitro experiment observed that stimulated by hypoxia andinflammatory factor, KLF2-overexpressed endothelial cells showed decreased proliferation,migration and vessel tube formation.We also found that, in KLF2-overexpressed cells, KLF2 downstream angiogenic factors such as Ang-2 and NF-κB level were inhibited while eNOS upregulated. Conclusion KLF2 level and angiogenesis were elevated in portal hypertension caused by cirrhosis. KLF2 may suppress the progress of angiogenesis via inhibiting the endothelial cells activation and modulating Ang-2 and NF-κB pathway.

P0199 : Acute kidney injury in cirrhosis: Baseline serum creatinine predicts patient outcomes

Background & Aims Intrahepatic and splanchnic angiogenesis plays an important role in Portal Hypertension (PHT) caused by cirrhosis. Krupple-like factor 2 (KLF2), a critical angiogenic protective factor, can maintain endothelial cellular phenotype by negatively regulating angiogenesis. Our research is to study whether KLF2 play a role in cirrhosisinduced PHT and its possible mechanism. Methods Human serum samples were collected from 41 PHT patients and 20 healthy subjects, and portal vessel tissue were obtained from 6 PHT patients and 6 cholecystitis controls during their surgeries. Rat models of portal vein ligation (PVL) and CCL4 were also used for our study. The expression of KLF2 and relevant angiogenic factors such asHIF-1α and VEGFwere evaluated. Additionally, human endothelial cells were used for vitro study. Lentivirus was transfected to overexpress KLF2. Tube formation and activation of cells were examined while KLF2 target protein expression were determined. Results We observed a remarkable upregluation of KLF2 in portal vein of PHT patients and angiogenic duodenum of PVL rats compared with controls, accompanied by a significant increasement of some relevant angiogenic factors such as VEGF and HIF-1α in PHT human and rat model. In addition, our vitro experiment observed that stimulated by hypoxia andinflammatory factor, KLF2-overexpressed endothelial cells showed decreased proliferation,migration and vessel tube formation.We also found that, in KLF2-overexpressed cells, KLF2 downstream angiogenic factors such as Ang-2 and NF-κB level were inhibited while eNOS upregulated. Conclusion KLF2 level and angiogenesis were elevated in portal hypertension caused by cirrhosis. KLF2 may suppress the progress of angiogenesis via inhibiting the endothelial cells activation and modulating Ang-2 and NF-κB pathway.

Patient-specific finite element analysis of ascending aorta aneurysms.

Catastrophic ascending aorta aneurysm (AsAA) dissection and rupture can be prevented by elective surgical repair, but identifying individuals at risk remains a challenge. Typically the decision to operate is based primarily on the overall aneurysm size, which may not be a reliable indicator of risk. In this study, AsAA inflation and rupture was simulated in 27 patient-specific finite element models constructed from clinical CT imaging data and tissue mechanical testing data from matching patients. These patients included n = 8 with concomitant bicuspid aortic valve (BAV), n = 10 with bovine aortic arch (BAA), and n = 10 with neither BAV nor BAA. AsAA rupture risk was found to increase with elevated systolic wall stress and tissue stiffness. The aortic size index was sufficient for identifying the patients with the lowest risk of rupture, but unsuitable for delineating between patients at moderate and high risk. There was no correlation between BAV or BAA and AsAA rupture risk; however, the AsAA morphology was different among these patients. These results support the use of mechanical parameters such as vessel wall stress and tissue stiffness for AsAA presurgical evaluation.