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Aortic diseases are characterized by dire prognosis and inadequate diagnosis, owing to their insidious yet lethal nature. Aortopathies, namely aortic aneurysms and dissections, along with certain congenital diseases, might necessitate surgical replacement of the aorta with vascular grafts. However, synthetic grafts present a challenge: they lack the necessary compliance, that is the aorta's capacity to accommodate the stroke volume by expanding. This phenomenon, termed "compliance mismatch", causes several post-operative complications, including hypertension and myocardial hypertrophy. Despite advances in graft technology, no synthetic grafts yet match the elasticity of healthy aortas. This dissertation aims to address the unmet need for compliant vascular grafts and to enhance the noninvasive monitoring techniques for aortic diseases and broader cardiovascular health.The first objective is to introduce a compliance-matching vascular graft with a layered biomimetic design. This design resembles a stent graft, comprised of a conventional graft, radially compressed by stents that regulate expansion and augment compliance. We employ finite element analysis to model this graft, utilizing the model for multiparameter computational optimization to elevate compliance. The fabrication followed by the in vitro assessment of our prototype grafts in an artificial circulatory system demonstrates that these grafts can achieve compliance within the physiological range under extensively varying conditions. The computational model can accurately predict the grafts' behavior, as manifested by its validation against experimental data. This optimization process paves the way for personalized grafts with tailored dimensions and compliance.Thereafter, we perform an acute preclinical evaluation of the compliance-matching grafts in swine. We design optimized compliance-matching grafts suitable for the porcine aorta, which are then implanted in the thoracic aorta of healthy pigs under cardiopulmonary bypass without any complications. The measurement of critical hemodynamic indices facilitates an extensive comparison among the healthy aortas, compliant grafts, and gold-standard grafts. Contrary to standard grafts, our compliance-matching grafts preserve the aortic stiffness and cardiac afterload at normal levels, without inducing hypertension. Our novel grafts could diminish the complications caused by compliance mismatch and surpass the performance of existing prostheses in clinical scenarios, potentially prolonging patient life expectancy.Finally, we delve into the optical and biomechanical influences on photoplethysmography (PPG), an emerging health monitoring technique. We suggest a theoretical model that elucidates the origins of the reflective PPG signal measured on an artery model within an in vitro circuit containing whole blood. Arterial pressure and blood flow rate, conveyed via the red blood cell (dis )orientation and (dis )aggregation, all contribute to the PPG signal. The proposed model aligns with experimental results and can resolve previous conflicting findings. Appropriate adaptation of this model could enable the noninvasive pressure waveform estimation and, combined with inverse or artificial intelligence algorithms, enhance the predictive accuracy of PPG devices for health monitoring, aortic disease detection, post-operative surveillance and, possibly, graft personalization.
Nikolaos Stergiopulos, Georgios Rovas
Nikolaos Stergiopulos, Georgios Rovas, Vasiliki Bikia
Yves Perriard, Yoan René Cyrille Civet, Thomas Guillaume Martinez, Francesco Clavica, Armando Matthieu Walter, Silje Ekroll Jahren, Lorenzo Ferrari