Introduction: The Ross procedure (aortic valve replacement with a pulmonary autograft) remains the gold standard in the pediatric population due to its growth potential and superior hemodynamics. However, the autograft is prone to dilation and maladaptive remodeling under systemic pressures, often resulting in late insufficiency and reoperation. Reinforcement strategies may mitigate this vulnerability, but permanent prosthetic materials constrain growth, while resorbable solutions remain experimental. Biofabrication and bioprinting technologies, particularly melt electrowriting (MEW), offers novel opportunities to design customizable biodegradable scaffolds. Hypothesis: A biodegradable extravascular scaffold can provide temporary mechanical support to the pulmonary autograft during its early maladaptive phase, preserving compliance while degrading as the graft stabilizes. Methods: A syngeneic rat model of the Ross operation was established. Four phases were conducted: development of the animal model, characterization of pulmonary root adaptation under systemic load, evaluation of non-degradable Gore-Tex® reinforcement, and design, mechanical testing, and preliminary in vivo assessment of MEW-fabricated polycaprolactone scaffolds. Results: The pulmonary autograft exhibited rapid dilation followed by stiffening and fibrotic remodeling, replicating mechanisms of human maladaptation. Gore-Tex reinforcement prevented dilation but induced loss of compliance and fibrotic encapsulation. MEW scaffolds demonstrated adequate mechanical properties approximating native aortic tissue. In vivo, they were surgically feasible and integrated into host tissue but provoked persistent inflammation and showed unpredictable degradation kinetics. Conclusions: This work provides mechanistic insights into autograft maladaptation and highlights both the promise and limitations of current reinforcement strategies with biodegradable extravascular scaffolds. Further refinement and validation in large-animal models are required before clinical translation.
EXTRAVASCULAR AORTIC ROOT REINFORCEMENT IN MURINE MODELS OF PULMONARY AUTOGRAFT (ROSS) OPERATION: FROM SYNTHETIC SCAFFOLDS TO BIOFABRICATED SUPPORTS / Guariento, A.. - (2026 Mar 26).
EXTRAVASCULAR AORTIC ROOT REINFORCEMENT IN MURINE MODELS OF PULMONARY AUTOGRAFT (ROSS) OPERATION: FROM SYNTHETIC SCAFFOLDS TO BIOFABRICATED SUPPORTS
GUARIENTO, ALVISE
2026
Abstract
Introduction: The Ross procedure (aortic valve replacement with a pulmonary autograft) remains the gold standard in the pediatric population due to its growth potential and superior hemodynamics. However, the autograft is prone to dilation and maladaptive remodeling under systemic pressures, often resulting in late insufficiency and reoperation. Reinforcement strategies may mitigate this vulnerability, but permanent prosthetic materials constrain growth, while resorbable solutions remain experimental. Biofabrication and bioprinting technologies, particularly melt electrowriting (MEW), offers novel opportunities to design customizable biodegradable scaffolds. Hypothesis: A biodegradable extravascular scaffold can provide temporary mechanical support to the pulmonary autograft during its early maladaptive phase, preserving compliance while degrading as the graft stabilizes. Methods: A syngeneic rat model of the Ross operation was established. Four phases were conducted: development of the animal model, characterization of pulmonary root adaptation under systemic load, evaluation of non-degradable Gore-Tex® reinforcement, and design, mechanical testing, and preliminary in vivo assessment of MEW-fabricated polycaprolactone scaffolds. Results: The pulmonary autograft exhibited rapid dilation followed by stiffening and fibrotic remodeling, replicating mechanisms of human maladaptation. Gore-Tex reinforcement prevented dilation but induced loss of compliance and fibrotic encapsulation. MEW scaffolds demonstrated adequate mechanical properties approximating native aortic tissue. In vivo, they were surgically feasible and integrated into host tissue but provoked persistent inflammation and showed unpredictable degradation kinetics. Conclusions: This work provides mechanistic insights into autograft maladaptation and highlights both the promise and limitations of current reinforcement strategies with biodegradable extravascular scaffolds. Further refinement and validation in large-animal models are required before clinical translation.| File | Dimensione | Formato | |
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Tesi dottorato Alvise Guariento 29092025.pdf
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