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Breast Capsular Contracture (BCC) is one of the adverse complications occurring with greater incidence in breast augmentation surgical procedures. Its formation can be interpreted as the conclusive result of the physiological process known as response to a foreign body. From a biochemical standpoint, the formation of the peri-prosthetic capsule is certainly a multifactorial process: many hypotheses concerning its etiology have been suggested in the literature and a number of related pharmacological protocols have been consequently proposed to clinically treat this pathology with the aim to prevent further complications and avoid future re-interventions. However, the vast majority of these theories seems to be only partially supported by clinical outcomes and thus a shared opinion on this matter is still absent among specialists. Within this framework, by starting from clinical observations which highlighted an unexpected correlation between histo-morphological features of fibrotic capsules and overall size of breast implants, the present study investigates the hypothesis that the biomechanical interaction between prosthesis and host tissue may play a crucial role in the biological processes governing the pathological phenomenon at hand. Therefore, to shed light on the underlying mechanisms which could trigger the breast capsular contracture, both simple analytical solutions, in which elasticity and growth are simultaneously taken into account, and more accurate geometrically faithful Finite Element-based numerical simulations have been exploited. The theoretical findings demonstrate that somehow counter-intuitive radial and hoop stress fields occur at the capsula-implant interface in a way such that their combined action, independently from other possible concurrent factors, results significantly amplified for small-size breast prostheses, localized stress peaks in these cases promoting detaching and rippling phenomena actually observed in BCC clinical complications., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (© 2016 Wiley Periodicals, Inc.)

Synthetic grafts are often satisfactory employed in cardiac and vascular surgery, including expanded poly(ethylene terephthalate) or expanded poly(tetrafluoroethylene). However, accumulating evidences suggest the emergence of worrisome issues concerning the long-term fate of prosthetic grafts as large vessel replacement. Disadvantages related to the use of synthetic grafts can be traced in their inability of mimicking the elasto-mechanical characteristics of the native vascular tissue, local suture overstress leading to several prosthesis-related complications and retrograde deleterious effects on valve competence, cardiac function and perfusion. Motivated by this, in the present work it is analyzed - by means of both elemental biomechanical paradigms and more accurate in silico Finite Element simulations - the physical interaction among aorta, autograft and widely adopted synthetic (Dacron) prostheses utilized in transposition of pulmonary artery, highlighting the crucial role played by somehow unexpected stress fields kindled in the vessel walls and around suture regions, which could be traced as prodromal to the triggering of anomalous remodelling processes and alterations of needed surgical outcomes. Theoretical results are finally compared with histological and surgical data related to a significant experimental animal campaign conducted by performing pulmonary artery transpositions in 30 two-month old growing lambs, followed up during growth for six months. The in vivo observations demonstrate the effectiveness of the proposed biomechanical hypothesis and open the way for possible engineering-guided strategies to support and optimize surgical procedures., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

Background: In patients with ischemic mitral regurgitation, leaflet prolapse requires an accurate evaluation since surgical approach depends on valvular and subvalvular characteristics. This study aims to describe a cohort of patients over a long-term follow up, analyzing survival, reoperation and predictive factors of surgical outcomes., Methods and Results: From March 1994 to June 2011, 75 patients with ischemic mitral regurgitation and leaflet prolapse underwent surgical myocardial revascularization and mitral valve repair (90.7%) or replacement (9.3%). Our cohort was followed up until April 2015, with a mean follow up of 7 ± 3 years. Cardiac-related deaths occurred in 26 patients, with a mean survival of 114.2 months, including eight patients with in-hospital mortality. Reoperation was performed in 14 patients, due to valve repair failure. Twenty-six patients experienced moderate-to-severe mitral regurgitation. A preoperative LVEDD > 62 mm, LVESD > 52 mm, previous anteroseptal myocardial infarction, diffuse coronary artery disease, papillary anatomy type 1, partial rupture of the papillary muscle, A1-A2 scallop prolapse and postoperative mitral valve configuration (tenting area, tenting height, alfa-1 angle and alfa-2 angle) were identified as independent predictors of poor outcome. An index quantifying the stress on the annulus imparted by annuloplasty was elaborated and predicted endpoints., Conclusion: Leaflet prolapse is an important entity in patients with ischemic mitral regurgitation, and its pathogenic mechanism mostly relies on papillary muscle lesion or elongation. Perioperative parameters describing geometric features of left ventricle, valvular and subvalvular components should be considered to provide a tailored approach for mitral valve repair, or to opt for immediate replacement in case of unfavorable geometry., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Computed tomography (CT) provides both anatomical and density information about tissues. Bone is segmented by raw images and Finite Element Method (FEM) voxel-based meshing technique is achieved by matching each CT voxel to a single finite element (FE). As a consequence of the automated model reconstruction, unstable elements - i.e. elements insufficiently anchored to the whole model and thus potentially involved in partial rigid body motion - can be generated, a crucial problem in obtaining consistent FE models, hindering mechanical analyses. Through the classification of instabilities on topological connections between elements, a numerical procedure is proposed in order to avoid unconstrained models.

Objectives: Use of resorbable external reinforcement of the pulmonary autograft during the Ross operation has been suggested, but the differential regional potential for dilation of the aorta, mainly regarding the neo-root and the neo-Valsalva sinuses, represents an unresolved issue. Auxetic materials could be useful in preventing dilation given their favorable mechanical properties. We designed a composite semiresorbable armoured bioprosthesis constituted by polydioxanone and expanded polytetrafluoroethylene and evaluated its effectiveness as a pulmonary autograft reinforcement device in an animal model of the Ross procedure., Methods: An experimental model of the Ross procedure was performed in 20 three-month-old growing lambs. The pulmonary autograft was alternatively nonreinforced (control group n = 10) or reinforced with composite bioprosthesis (reinforced group n = 10). Animals were followed up during growth for 6 months by angiography and echocardiography. Specific stainings for extracellular matrix and immunohistochemistry for metalloproteinase-9 were performed., Results: Reference aortic diameter increased from 14 ± 1 mm to 19 ± 2 mm over 6 months of growth. In the control group, pulmonary autograft distension (28 ± 2 mm) was immediately noted, followed by aneurysm development at 6 months (40 ± 2 mm, P < .001 vs reference). In the reinforced group, an initial dilation to 18 ± 1 mm was detected and the final diameter was 27 ± 2 mm (42% increase). Two deaths due to pulmonary autograft rupture occurred in the control group. On histology, the control group showed medial disruption with connective fibrous replacement, whereas in the reinforced group compensatory intimal hyperplasia was present in the absence of intimal tears. The bioprosthesis promoted a positive matrix rearrangement process favoring neoarterialization and elastic remodeling as demonstrated on specific staining for elastin collagen and metalloproteinase-9., Conclusions: The device adapted and functionally compensated for the characteristics of autograft growth, guaranteeing a reasonable size of the autograft at 6 months, but more important, because the device is biocompatible, it did not disrupt the biological process of growth or cause inflammatory damage to the wall., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Supravalvular pulmonary stenosis (SPS) remains a worrisome complication in the long term of simple transposition of the great arteries. Issues of scar formation and inability to grow are considered at the base of this phenomenon. We pioneered the use of a tissue engineering approach to guide the maturation and the growth of pulmonary autograft in the Ross procedure with encouraging results. We therefore sought to investigate the use of a similar approach in the reconstruction of neopulmonary trunk (NPT) with the aim to recreate a vascular conduit that retains the structural architecture and the same biological potential of native pulmonary artery and prevents long-term SPS., Methods: A model of NPT reconstruction in growing lambs was used. NPT was constructed with autologous pericardium and reinforced with a four-layered knitted polydioxanone mesh (PDS n=10) or left unreinforced (control n=10). Animals were left growing for 6 months and angiographic and transesophageal echocardiographic measurements were performed at day 1 and at the end of the study together with histological analysis., Results: Control group developed SPS while PDS reinforcement allowed a progressive increase in diameter with an optimal size to match the pulmonary artery of healthy growing controls. Histological analysis showed in the control group disruption of endothelial lining with fibrosis, while demonstrated in the PDS group a trilaminar vessel-like structure., Conclusions: The bioresorbable reinforcement induced the formation over time of a neopulmonary conduit able to both face the hemodynamic load of the pulmonary system and guarantee a harmonious increase in size during the somatic growth., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Experimental studies recently performed on single cancer and healthy cells have demonstrated that the former are about 70% softer than the latter, regardless of the cell lines and the measurement technique used for determining the mechanical properties. At least in principle, the difference in cell stiffness might thus be exploited to create mechanical-based targeting strategies for discriminating neoplastic transformations within human cell populations and for designing innovative complementary tools to cell-specific molecular tumour markers, leading to possible applications in the diagnosis and treatment of cancer diseases. With the aim of characterizing and gaining insight into the overall frequency response of single-cell systems to mechanical stimuli (typically low-intensity therapeutic ultrasound), a generalized viscoelastic paradigm, combining classical and spring-pot-based models, is introduced for modelling this problem by neglecting the cascade of mechanobiological events involving the cell nucleus, cytoskeleton, elastic membrane and cytosol. Theoretical results show that differences in stiffness, experimentally observed ex vivo and in vitro, allow healthy and cancer cells to be discriminated, by highlighting frequencies (from tens to hundreds of kilohertz) associated with resonance-like phenomena—prevailing on thermal fluctuations—that could be helpful in targeting and selectively attacking tumour cells., (© 2015 The Author(s).)

A mechanical analysis of the conductive keratoplasty on hyperopic eyes has been carried out, and the attention has been focused on incorporating the actual viscoelastic properties of the human corneal tissue and on the stress gradients induced by the intervention. By avoiding unnecessary complications which may obscure the essential behaviour of the model, the results are in very good agreement with the clinical and experimental findings and suggest that the major role in the commonly observed decrease of the initial degree of the refractive correction might be played by the stress gradients at the intervention spots, which are likely to influence the wound-healing. The study aims to contribute some firm mechanical roots to the predictability of the outcome of an increasingly popular technique that, notwithstanding several advantages with respect to ablative interventions, at present cannot be considered completely satisfactory.

With particular interest on total hip arthroplasty (THA), optimization of orthopedic prostheses is employed in this work to minimize the probability of implant failure or maximize prosthesis reliability. This goal is often identified with the reduction of stress concentrations at the interface between bone and these devices. However, aseptic loosening of the implant is mainly influenced by bone resorption phenomena revealed in some regions of the femur when a prosthesis is introduced. As a consequence, bone resorption appears due to stress shielding, that is to say the decrease of the stress level in the implanted femur caused by the significant load carrying of the prosthesis due to its higher stiffness. A maximum stiffness topological optimization-based (TO) strategy is utilized for non-linear static finite element (FE) analyses of the femur-implant assembly, with the goal of reducing stress shielding in the femur and to furnish guidelines for re-designing hip prostheses. This is accomplished by employing an extreme accuracy for both the three- dimensional reconstruction of the femur geometry and the material properties maps assigned as explicit functions of the local densities.