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Experimental and Numerical Analysis of Growth and Remodeling Phenomena in the Pulmonary Autograft

Boek - Dissertatie

In several cardiac interventions, pulmonary arterial tissue is exposed to systemic conditions. One of these procedures is the Ross procedure, which replaces a diseased aortic valve with the patient's own pulmonary valve. A common complication hereby is the dilatation of this pulmonary autograft. Still, not all autografts fail and the decisive factor for autograft failure is not known. Several reinforcement strategies have been designed to counteract this dilatation, but none have proven to be consistently successful. A personalized macroporous mesh used to reinforce dilating aortic roots in Marfan patients might also bring a solution for this dilating autograft. The goal of this thesis is therefore to investigate the mechanical and microstructural changes that occur when a pulmonary artery is placed in aortic position as an autograft, and to assess the effect of a macroporous mesh that reinforces the autograft. To this end, a combined experimental and computational approach was applied. Two sets of experiments were conducted on sheep. Within these animal experiments, a segment of pulmonary artery was placed in aortic position. This pulmonary autograft was either reinforced with a macroporous mesh or left unreinforced in the control group. Six months after implantation, the sheep were sacrificed and the following tissues were harvested and subjected to planar biaxial testing: native aorta, native pulmonary artery, unreinforced pulmonary autograft, reinforced pulmonary autograft. The first set of animal experiments constisted of nine sheep, with two sheep serving as control group. Seventeen sheep were included in the second set of animal experiments, with eight sheep serving as control group. The mechanical behavior of the unreinforced autograft adapted to become more aorta-like in some samples whereas it retained its pulmonary artery character in other samples. Microstructurally, an increased collagen deposition, smooth muscle cell atrophy and a decrease in media thickness occured in the unreinforced pulmonary autograft. The mesh appeared to be nicely incorporated but a higher loss of smooth muscle cells was noticed in the reinforced pulmonary autograft. The follow-up MRIs, taken only in the second set of animal experiments, showed progressive dilatation of the autograft when leaving it unreinforced. The macroporous mesh around the pulmonary autograft decreased autograft dilatation, but also its compliance.A subset of animal experiments without macroporous reinforcement was reproduced in silico using different growth and remodeling models. The ability to reproduce the experimental outcome was evaluated for two types of models: models based on kinematic growth theory and models based on constrained mixture theory. The former decompose the deformation gradient into a growth and elastic deformation gradient, with growth either in the radial or circumferential direction. The constrained mixture theory represents an artery as a mixture of constituents with their own stress-free configuration, turnover rates and material properties, but are constrained to move together. The two constituents in this case are elastin and collagen. Elastin is assumed to remain constant whereas collagen continuously degrades and is deposited, influenced by the stretch felt by the collagen fibers. The kinematic growth model with circumferential growth as well as the constrained mixture models are capable of reproducing the progressive dilatation of the autograft. However, where the experiments show an initial steep increase in diameter followed by a slower increase, the model shows a linearly increasing diameter. As opposed to the kinematic growth models, the constrained mixture models are also able to reproduce the experimentally observed changes in mechanical behaviour and collagen fraction. In conclusion, the animal experiments showed adaptation of the mechanical behavior of the pulmonary artery when placed in aortic position. The macroporous mesh was also able to halt progressive dilatation of the autograft while retaining its microstructure. The two types of growth and remodeling models were capable of simulating the dilatation of the autograft, and the constrained mixture models were also capable of simulating changing mechanical behavior and microstructure. Nevertheless, more controlled experiments are needed to increase our understanding of autograft (mal)adaptation and to define more mechanobiologically substantiated constitutive relations.
Jaar van publicatie:2020