The pulmonary artery autograft (PA) is the ideal substitute for aortic valve disease in children and young adult. However, it is harnessed by the issue of long-term dilation and regurgitation, often requiring surgery. PA implanted in aortic position during the growth phase in children undergoes a process of mechanical remodeling. We previously developed a semiresorbable armored prosthesis able to mechanically sustain the neoaorta preventing dilation and to gradually integrate with the PA wall inducing a progressive arterial-like tissue positive remodeling. We also described the mechanisms of growth, remodeling and stress shielding of the reinforced PA through a mathematical model. We sought to demonstrate the biological counterpart and the potential molecular mechanisms underlying this histological and mechanical remodeling. A specific mathematical model was developed to describe mechanical behavior of the PA. Mallory trichrome red staining and immunohistochemistry for MMP-9 were performed to elucidate extracellular matrix remodeling phenomena. Apoptosis and cell proliferation were determined by TUNEL assay and immunohistochemistry for Ki67, respectively. An histological remodeling phenomenon sustained by increased level of MMP-9, augmented cell proliferation and reduced apoptosis in the reinforced PA was demonstrated. The mathematical model predicted the biomechanical behavior subtended by the histological changes of the PA in these settings. Changes in metalloproteinases (MMP-9), cell proliferation and apoptosis are the main actors in the remodeling process occurring after transposition of the PA into systemic regimens. Use of semiresorbable reinforcements might induce a positive remodeling of the PA in the context of Ross operation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2785-2793, 2016.

Ross operation, i.e., the use of autologous pulmonary artery to replace diseased aortic valve, has been recently at the center of a vivid debate regarding its unjust underuse in the surgical practice. Keystone of the procedure regards the use of an autologous biologically available graft which would preserve the anticoagulative and tissue homeostatic functions normally exerted by the native leaflets and would harmoniously integrate in the vascular system, allowing for progressive somatic growth of aortic structures. With this respect, recently, some of the authors have successfully pioneered a large animal model of transposition of pulmonary artery in systemic pressure load in order to reproduce the clinical scenario in which this procedure might be applied and allow for the development and testing of different devices or techniques to improve the pulmonary autograft (PA) performance, by testing a bioresorbable mesh for PA reinforcement. In the present work, to support and supplement the in vivo animal experimentation, a mathematical model is developed in order to simulate the biomechanical changes in pulmonary artery subjected to systemic pressure load and reinforced with a combination of resorbable and auxetic synthetic materials. The positive biological effects on vessel wall remodeling, the regional somatic growth phenomena and prevention of dilatative degeneration have been analyzed. The theoretical outcomes show that a virtuous biomechanical cooperation between biological and synthetic materials takes place, stress-shielding guiding the physiological arterialization of vessel walls, consequently determining the overall success of the autograft system.

The absence of reinforcement leads to a more marked increase in the diameter of the PA. Preservation of the native geometry of the PA root is crucial; the miniroot technique with external reinforcement is the most suitable strategy in this context.

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Tensegrity structures are special architectures made by floating compressed struts kept together by a continuous system of tensioned cables. Their existence in a mechanically stable form is decided by the possibility of finding geometrical configurations such that pre-stressed tendons and bars can ensure self-equilibrium of the forces transmitted through the elastic network, the overall stiffness of which finally depends on both the rigidity of the compressed elements and the cables' pre-stress. The multiplicity of shapes that tensegrity structures can assume and their intrinsic capability to be deployable and assembled, so storing (and releasing) elastic energy, have motivated their success as paradigm -pioneeringly proposed three decades ago by the intuition of Donald E. Ingber-to explain some underlying mechanisms regulating dynamics of living cells. The interlaced structure of the cell cytoskeleton, constituted by actin microfilaments, intermediate filaments and microtubules which continuously change their spatial organization and pre-stresses through polymerization/depolymerization processes, seems in fact to steer migration, adhesion and arXiv:1904.04610v1 [physics.bio-ph] 9 Apr 2019 cell division by obeying the tensegrity construct. Even though rough calculations lead to estimate discrepancies of less than one order of magnitude when comparing axial stiffness of actin filaments (cables) and microtubules (struts) and recent works have shown bent microtubules among stretched filaments, no one has yet tried to remove the standard hypothesis of rigid struts in tensegrity structures when used to idealize the cell cytoskeleton mechanical response. With reference to the 30-element tensegrity cell paradigm, we thus introduce both compressibility and bendability of the struts and accordingly rewrite the theory to simultaneously take into account geometrical non-linearity (i.e. large deformations) and hyper-elasticity of both tendons and bars, so abandoning the classical linear stress-strain constitutive assumptions. By relaxing the hypothesis of rigidity of the struts, we demonstrate that some quantitative confirmations and many related extreme and somehow counterintuitive mechanical behaviors actually exploited by cells for storing/releasing energy, resisting to applied loads and deforming by modulating their overall elasticity and shape through pre-stress changes and instability-guided configurational switching, can be all theoretically found. It is felt that the proposed new soft-strut tensegrity model could pave the way for a wider use of engineering models in cell mechanobiology and in designing bio-inspired materials and soft robots.

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