Development and assessment of case-specific physical and augmented reality simulators for intracranial aneurysm clipping.

BACKGROUND: Microsurgical clipping is a delicate neurosurgical procedure used to treat complex Unruptured Intracranial Aneurysms (UIAs) whose outcome is dependent on surgeon's experience. Simulations are emerging as excellent complements to standard training, but their adoption is limited by the realism they provide. The aim of this study was to develop and validate a microsurgical clipping simulator platform. METHODS: Physical and holographic simulators of UIA clipping have been developed. The physical phantom consisted of a 3D printed hard skull and five (n = 5) rapidly interchangeable, perfused and fluorescence compatible 3D printed aneurysm silicone phantoms. The holographic clipping simulation included a real-time finite-element-model of the aneurysm sac, allowing interaction with a virtual clip and its occlusion. Validity, usability, usefulness and applications of the simulators have been assessed through clinical scores for aneurysm occlusion and a questionnaire study involving 14 neurosurgical residents (R) and specialists (S) for both the physical (p) and holographic (h) simulators by scores going from 1 (very poor) to 5 (excellent). RESULTS: The physical simulator allowed to replicate successfully and accurately the patient-specific anatomy. UIA phantoms were manufactured with an average dimensional deviation from design of 0.096 mm and a dome thickness of 0.41 ± 0.11 mm. The holographic simulation executed at 25-50 fps allowing to gain unique insights on the anatomy and testing of the application of several clips without manufacturing costs. Aneurysm closure in the physical model evaluated by fluorescence simulation and post-operative CT revealed Raymond 1 (full) occlusion respectively in 68.89% and 73.33% of the cases. For both the simulators content validity, construct validity, usability and usefulness have been observed, with the highest scores observed in clip selection usefulness Rp=4.78, Sp=5.00 and Rh=4.00, Sh=5.00 for the printed and holographic simulators. CONCLUSIONS: Both the physical and the holographic simulators were validated and resulted usable and useful in selecting valid clips and discarding unsuitable ones. Thus, they represent ideal platforms for realistic patient-specific simulation-based training of neurosurgical residents and hold the potential for further applications in preoperative planning.

Fluid dynamics characterization and thrombogenicity assessment of a levitating centrifugal pump with different impeller designs.

Technical guidelines nowadays recommend and regulate the use Computational Fluid Dynamics (CFD) to assess the performance of medical devices. CFD coupled to blood damage models has emerged as a powerful tool to evaluate the hemocompatibility of blood recirculating devices. The present study is aimed at evaluating the hydrodynamic performance and the thrombogenic potential of two prototypes of magnetically levitating centrifugal pumps. The two devices differ in the impeller configuration - 6-blades vs. 12-blades - and have been designed to be used in Cardiopulmonary Bypass (CPB) circuits during open heart surgery and in Extracorporeal Membrane Oxygenation (ECMO) to support patients with severe cardiac or respiratory failure. The pumps have been modelled using Direct Numerical Simulation coupled to Lagrangian analysis to predict platelet activation due to abnormal shear stress histories. Numerical results have been compared with experimental data in terms of head generation for different working points. Results show that the 6-blades pump has i) smaller stagnation areas, ii) lower stress levels and iii) higher strain rate, resulting in a lower thrombogenic potential, whereas the 12-blade impeller guarantees a more stable performance at high flow rates, suggesting its preferential use for more demanding applications, such as CPB.

Electrospun fibroin/polyurethane hybrid meshes: Manufacturing, characterization, and potentialities as substrates for haemodialysis arteriovenous grafts.

Several attempts made so far to combine silk fibroin and polyurethane, in order to prepare scaffolds encompassing the bioactivity of the former with the elasticity of the latter, suffer from critical drawbacks concerning industrial and clinical applicability (e.g., separation of phases upon processing, use of solvents unaddressed by the European Pharmacopoeia, and use of degradable polyurethanes). Overcoming these limitations, in this study, we report the successful blending of regenerated silk fibroin with a medical-grade, non-degradable polyurethane using formic acid and dichloromethane, and the manufacturing of hybrid, semi-degradable electrospun tubular meshes with different ratios of the two materials. Physicochemical analyses demonstrated the maintenance of the characteristic features of fibroin and polyurethane upon solubilization, blending, electrospinning, and postprocessing with ethanol or methanol. Envisioning their possible application as semidegradable substrates for haemodialysis arteriovenous grafts, tubular meshes were further characterized, showing submicrometric fibrous morphologies, tunable mechanical properties, permeability before and after puncture in the same order of magnitude as commercial grafts currently used in the clinics. Results demonstrate the potential of this material for the development of hybrid, new-generation vascular grafts with disruptive potential in the field of in situ tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 807-817, 2019.

A novel hybrid silk-fibroin/polyurethane three-layered vascular graft: towards in situ tissue-engineered vascular accesses for haemodialysis.

Clinically available alternatives of vascular access for long-term haemodialysis-currently limited to native arteriovenous fistulae and synthetic grafts-suffer from several drawbacks and are associated to high failure rates. Bioprosthetic grafts and tissue-engineered blood vessels are costly alternatives without clearly demonstrated increased performance. In situ tissue engineering could be the ideal approach to provide a vascular access that profits from the advantages of vascular grafts in the short-term (e.g. early cannulation) and of fistulae in the long-term (e.g. high success rates driven by biointegration). Hence, in this study a three-layered silk fibroin/polyurethane vascular graft was developed by electrospinning to be applied as long-term haemodialysis vascular access pursuing a 'hybrid' in situ engineering approach (i.e. based on a semi-degradable scaffold). This Silkothane® graft was characterized concerning morphology, mechanics, physical properties, blood contact and vascular cell adhesion/viability. The full three-layered graft structure, influenced by the polyurethane presence, ensured mechanical properties that are a determinant factor for the success of a vascular access (e.g. vein-graft compliance matching). The Silkothane® graft demonstrated early cannulation potential in line with self-sealing commercial synthetic arteriovenous grafts, and a degradability driven by enzymatic activity. Moreover, the fibroin-only layers and extracellular matrix-like morphology, presented by the graft, revealed to be crucial in providing a non-haemolytic character, long clotting time, and favourable adhesion of human umbilical vein endothelial cells with increasing viability after 3 and 7 d. Accordingly, the proposed approach may represent a step forward towards an in situ engineered hybrid vascular access with potentialities for vein-graft anastomosis stability, early cannulation, and biointegration.

4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical Remodeling.

Bicuspid aortic valve (BAV) is the most common congenital cardiac disease and is a foremost risk factor for aortopathies. Despite the genetic basis of BAV and of the associated aortopathies, BAV-related alterations in aortic fluid-dynamics, and particularly in wall shear stresses (WSSs), likely play a role in the progression of aortopathy, and may contribute to its pathogenesis. To test whether WSS may trigger aortopathy, in this study we used 4D Flow sequences of phase-contrast cardiac magnetic resonance imaging (CMR) to quantitatively compare the in vivo fluid dynamics in the thoracic aorta of two groups of subjects: (i) five prospectively enrolled young patients with normo-functional BAV and with no aortic dilation and (ii) ten age-matched healthy volunteers. Through the semi-automated processing of 4D Flow data, the aortic bulk flow at peak systole was quantified, and WSSs acting on the endothelium of the ascending aorta were characterized throughout the systolic phase in terms of magnitude and time-dependency through a method recently developed by our group. Variables computed for each BAV patient were compared vs. the corresponding distribution of values obtained for healthy controls. In BAV patients, ascending aorta diameter was measured on cine-CMR images at baseline and at 3-year follow-up. As compared to controls, normo-functional BAV patients were characterized by minor bulk flow disturbances at peak systole. However, they were characterized by evident alterations of WSS distribution and peak values in the ascending aorta. In particular, in four BAV patients, who were characterized by right-left leaflet fusion, WSS peak values exceeded by 27-46% the 90th percentile of the distribution obtained for healthy volunteers. Only in the BAV patient with right-non-coronary leaflet fusion the same threshold was exceeded by 132%. Also, evident alterations in the time-dependency of WSS magnitude and direction were observed. Despite, these fluid-dynamic alterations, no clinically relevant anatomical remodeling was observed in the BAV patients at 3-year follow-up. In light of previous evidence from the literature, our results suggest that WSS alterations may precede the onset of aortopathy and may contribute to its triggering, but WSS-driven anatomical remodeling, if any, is a very slow process.