Fractional-order poromechanics for a fully saturated biological tissue: Biomechanics of meniscus.

Biomechanics of biological fibrous tissues as the meniscus are strongly influenced by past histories of strains involving the so-called material hereditariness. In this paper, a three-axial model of linear hereditariness that makes use of fractional-order calculus is used to describe the constitutive behavior of the tissue. Fluid flow across meniscus' pores is modeled in this paper with Darcy relation yielding a novel model of fractional-order poromechanics, describing the evolution of the diffusion phenomenon in the meniscus. A numerical application involving an 1D confined compression test is reported to show the effect of the material hereditariness on the pressure drop evolution.

Carotid Artery Disease in the Era of Biomarkers: A Pilot Study.

The intima-media thickness (IMT) and its irregularities or ulcerations in the common carotid artery (CCA) are useful tools as sentinel biomarkers for the integrity of the cardiovascular system. Total homocysteine and lipoprotein levels are the most commonly used elements in cardiovascular risk stratification. Duplex ultrasound (DUS), associated with serum biomarkers, can be used simply to assess the degree of atherosclerotic disease and cardiovascular risk. This study highlights the role of different kinds of biomarkers, showing their usefulness and potentiality in multi-district atherosclerotic patients, especially for early diagnosis and therapy effectiveness monitoring. A retrospective analysis performed from September 2021 to August 2022, of patients with carotid artery disease, was performed. A total of 341 patients with a mean age of 53.8 years were included in the study. The outcomes showed an increased risk of stroke in patients with significative carotid artery disease, nonresponsive to therapy, monitored through a series of serum biomarkers (homocysteine, C-reactive protein, and oxidized LDL). In this reported experience, the systematic use of DUS in association with the multiple biomarkers approach was effective for the early identification of patients at higher risk of disease progression or inefficient therapy.

Polybutylene Succinate Processing and Evaluation as a Micro Fibrous Graft for Tissue Engineering Applications.

A microfibrous tubular scaffold has been designed and fabricated by electrospinning using poly (1,4-butylene succinate) as biocompatible and biodegradable material. The scaffold morphology was optimized as a small diameter and micro-porous conduit, able to foster cell integration, adhesion, and growth while avoiding cell infiltration through the graft's wall. Scaffold morphology and mechanical properties were explored and compared to those of native conduits. Scaffolds were then seeded with adult normal human dermal fibroblasts to evaluate cytocompatibility in vitro. Haemolytic effect was evaluated upon incubation with diluted whole blood. The scaffold showed no delamination, and mechanical properties were in the physiological range for tubular conduits: elastic modulus (17.5 ± 1.6 MPa), ultimate tensile stress (3.95 ± 0.17 MPa), strain to failure (57 ± 4.5%) and suture retention force (2.65 ± 0.32 N). The shown degradation profile allows the graft to provide initial mechanical support and functionality while being colonized and then replaced by the host cells. This combination of features might represent a step toward future research on PBS as a biomaterial to produce scaffolds that provide structure and function over time and support host cell remodelling.

Patient-specific computational evaluation of stiffness distribution in ascending thoracic aortic aneurysm.

Quantifying local aortic stiffness properties in vivo is acknowledged as essential to assess the severity of an ascending thoracic aortic aneurysm (ATAA). Recently, the LESI (local extensional stiffness identification) methodology has been established to quantify non-invasively local stiffness properties of ATAAs using electrocardiographic-gated computed tomography (ECG-gated CT) scans. The aim of the current study was to determine the most sensitive markers of local ATAA stiffness estimation with the hypothesis that direct measures of local ATAA stiffness could better detect the high-risk patients. A cohort of 30 patients (12 BAV and 18 TAV) referred for aortic size evaluation by ECG-gated CT were recruited. For each patient, the extensional stiffness Q was evaluated by the LESI methodology whilst computational flow analyses were also performed to derive hemodynamics markers such as the wall shear stress (WSS). A strong positive correlation was found between the extensional stiffness and the aortic pulse pressure (R = 0.644 and p < 0.001). Interestingly, a significant positive correlation was also found between the extensional stiffness and patients age for BAV ATAAs (R = 0.619 and p = 0.032), but not for TAV ATAAs (R = -0.117 and p = 0.645). No significant correlation was found between the extensional stiffness and WSS evaluated locally. There was no significant difference either in the extensional stiffness between BAV ATAAs and TAV ATAAs (Q = 3.6 ± 2.5 MPa.mm for BAV ATAAs vs Q = 5.3 ± 3.1 MPa.mm for TAV ATAAs, p = 0.094). Future work will focus on relating the extensional stiffness to the patient-specific rupture risk of ATAAs on larger cohorts to confirm the promising interest of the LESI methodology.

How preconditioning and pretensioning of grafts used in ACLigaments surgical reconstruction are influenced by their mechanical time-dependent characteristics: Can we optimize their initial loading state?

PURPOSE: Consensus about a pre-implant preparation protocol adaptable to any graft used in Anterior Cruciate Ligament reconstruction is still lacking. In fact, there is not agreement on reliable metrics that consider both specific graft dimensional characteristics, such as its diameter, and the inherent properties of its constitutive material, i.e. ligaments or tendons. Aim of the present study was to investigate and propose the applied engineering stress as a possible metrics. METHODS: Preconditioning and pretensioning protocol involved groups of grafts with different section (10 or 32 mm2) and materials (i.e. human patellar and hamstring tendons, and synthetic grafts). A 140 N load was applied to the grafts and maintained for 100 s. Initial stress and following stress-relaxation (a mechanical characteristic that can be related to knee laxity) were specifically analysed. FINDINGS: Initial stress, ranging between 4 and 12 MPa, was affected primarily by the graft cross-section area and secondarily by the choice of the graft material. In terms of loss of the initial stress, stress-relaxation behaviour varied instead on a narrower range, namely 13-17%. INTERPRETATION: Engineering stress can be identified as the correct metrics to optimize the initial state of each graft to avoid excessive stiffness, laxity or fatigue rupture phenomena.

Advanced materials modelling via fractional calculus: challenges and perspectives.

Fractional calculus is now a well-established tool in engineering science, with very promising applications in materials modelling. Indeed, several studies have shown that fractional operators can successfully describe complex long-memory and multiscale phenomena in materials, which can hardly be captured by standard mathematical approaches as, for instance, classical differential calculus. Furthermore, fractional calculus has recently proved to be an excellent framework for modelling non-conventional fractal and non-local media, opening valuable prospects on future engineered materials. The theme issue gathers cutting-edge theoretical, computational and experimental studies on advanced materials modelling via fractional calculus, with a focus on complex phenomena and non-conventional media. This article is part of the theme issue 'Advanced materials modelling via fractional calculus: challenges and perspectives'.

Mechanobiology predicts raft formations triggered by ligand-receptor activity across the cell membrane.

Clustering of ligand-binding receptors of different types on thickened isles of the cell membrane, namely lipid rafts, is an experimentally observed phenomenon. Although its influence on cell's response is deeply investigated, the role of the coupling between mechanical processes and multiphysics involving the active receptors and the surrounding lipid membrane during ligand-binding has not yet been understood. Specifically, the focus of this work is on G-protein-coupled receptors (GPCRs), the widest group of transmembrane proteins in animals, which regulate specific cell processes through chemical signalling pathways involving a synergistic balance between the cyclic Adenosine Monophosphate (cAMP) produced by active GPCRs in the intracellular environment and its efflux, mediated by the Multidrug Resistance Proteins (MRPs) transporters. This paper develops a multiphysics approach based on the interplay among energetics, multiscale geometrical changes and mass balance of species, i.e. active GPCRs and MRPs, including diffusion and kinetics of binding and unbinding. Because the obtained energy depends upon both the kinematics and the changes of species densities, balance of mass and of linear momentum are coupled and govern the space-time evolution of the cell membrane. The mechanobiology involving remodelling and change of lipid ordering of the cell membrane allows to predict dynamics of transporters and active receptors -in full agreement with experimentally observed cAMP levels- and how the latter trigger rafts formation and cluster on such sites. Within the current scientific debate on Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) and on the basis of the ascertained fact that lipid rafts often serve as an entry port for viruses, it is felt that approaches accounting for strong coupling among mechanobiological aspects could even turn helpful in better understanding membrane-mediated phenomena such as COVID-19 virus-cell interaction.

Identification of circumferential regional heterogeneity of ascending thoracic aneurysmal aorta by biaxial mechanical testing.

Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) can present an asymmetrical aortic dilatation compared with patients with tricuspid aortic valve (TAV). This pattern of aneurysm dilatation led us to hypothesize that biomechanical differences likely induced by regional heterogeneity of material properties can underlie the observed asymmetric enlargement discrepancies between BAV ATAA and TAV ATAA. This study aimed to characterize the mechanical properties and associated aortic tissue stiffness changes along the circumferential direction of aortic rings collected from surgically-repaired patients with ATAA. Biaxial material testing was performed on tissue specimens extrapolated from all aortic quadrants (i.e. anterior, posterior, major and minor curvature of the aorta), and then the tissue stiffness was quantified at both physiological and supra-physiological stress levels (i.e. 142 kPa and 242 kPa, respectively). Tissue stiffness revealed that the major curvature of BAV ATAA is statistically less stiff than the anterior quadrant (276.6 ±â€¯137.1 kPa for BAV ATAA and 830.1 ±â€¯557.1 kPa for BAV ATAA, p = .024, at 142 kPa) and to that of major curvature of TAV ATAA (276.6 ±â€¯137.0 kPa for BAV ATAA and 733.2 ±â€¯391.1 kPa for TAV ATAA, p = .001, at 142 kPa), suggesting local weakening of bicuspid aortic wall. Multiphoton imaging revealed local changes on elastic fiber networks. The recovered material parameters for the Fung-type constitutive model are crucial for reliable stress predictions while the information on regional tissue stiffness changes are fundamental to develop risk stratification strategies not based on aortic size.

On the role of material properties in ascending thoracic aortic aneurysms.

One of the obstacles standing before the biomechanical analysis of an ascending thoracic aortic aneurysm (ATAA) is the difficulty in obtaining patient-specific material properties. This study aimed to evaluate differences on ATAA-related stress predictions resulting from the elastostatic analysis based on the optimization of arbitrary material properties versus the application of patient-specific material properties determined from ex-vivo biaxial testing. Specifically, the elastostatic analysis relies the on the fact that, if the aortic wall stress does not depend on material properties, the aorta has to be statistically determinate. Finite element analysis (FEA) was applied to a group of nine patients who underwent both angio-CT imaging to reconstruct ATAA anatomies and surgical repair of diseased aorta to collect tissue samples for experimental material testing. Tissue samples cut from excised ATAA rings were tested under equibiaxial loading conditions to obtain experimentally-derived material parameters by fitting stress-strain profiles. FEAs were carried out using both optimized and experimentally-derived material parameters to predict and compare the stress distribution using the mean absolute percentage error (MAPE). Although physiological strains were below yield point (range of 0.08-0.25), elastostatic analysis led to errors on the stress predictions that depended on the type of constitutive model (highest MAPE of 0.7545 for Yeoh model and 0.7683 for Fung model) and ATAA geometry (lowest MAPE of 0.0349 for patient P.7). Elastostatic analysis needs better understanding of its application for determining aneurysm mechanics, and patient-specific material parameters are essential for reliable accurate stress predictions in ATAAs.

Enhanced In Situ Availability of Aphanizomenon Flos-Aquae Constituents Entrapped in Buccal Films for the Treatment of Oxidative Stress-Related Oral Diseases: Biomechanical Characterization and In Vitro/Ex Vivo Evaluation.

In recent years, the key role of oxidative stress in pathogenesis of oral diseases has been emphasized and the use of antioxidant agents has been encouraged. Aphanizomenon flos-aquae (AFA) is a unicellular blue-green alga with antioxidant and anti-inflammatory properties. The aim of this study was the formulation and characterization of mucoadhesive thin layer films loaded with AFA, finalized to the treatment of oxidative stress (OS)-related oral diseases. First, to enhance the bioavailability of AFA constituents, the raw food grade material was appropriately treated by a high frequency homogenization able to disrupt cell walls. Thus, Eudragit® E100-based buccal films were produced by the solvent casting method, containing 7% and 18% of AFA. The films, characterized by uniformity in thickness, weight, and drug content, showed low swelling degree, good muco-adhesiveness and controlled drug release. The mechanical tests showed elastic moduli of films of almost 5 MPa that is well-suitable for human buccal applications without discomfort, besides biaxial tests highlighted a marked material isotropy. Permeation studies through porcine mucosae demonstrated the ability of films to promote AFA penetration in the tissues, and when sublingually administered, they produced a drug flux up to six-fold higher than an AFA solution. The new formulations represent an interesting alternative for the development of cosmetics and nutraceuticals with a functional appeal containing plant extracts.

Multifibrillar bundles of a self-assembling hyaluronic acid derivative obtained through a microfluidic technique for aortic smooth muscle cell orientation and differentiation.

A hyaluronic acid derivative that is able to physically crosslink in a saline aqueous environment was employed for the production of fibers with a mean diameter of 50 µm using a microfluidic technique. The microfibers were collected in a tailored rotating collector and assembled to form multifibrillar bundles. The orientation of the microfibers on the collected bundles was evaluated by microCT analysis. The bundles were biofunctionalized by physical addition of fibronectin or chemical tethering of a cyRGDC peptide to achieve control of Aortic Smooth Muscle Cell (AoSMC) attachment, elongation and alignment. The mechanical performances of these bundles were evaluated by elongation tests, related to the kind of biological functionalization and compared to non-functionalized samples. The alignment and differentiation of AoSMCs on single fibers and on the bundles were evaluated by microscopy and histochemical analyses.

Power-law hereditariness of hierarchical fractal bones.

In this paper, the authors introduce a hierarchic fractal model to describe bone hereditariness. Indeed, experimental data of stress relaxation or creep functions obtained by compressive/tensile tests have been proved to be fit by power law with real exponent 0 ⩽ ß â©½1. The rheological behavior of the material has therefore been obtained, using the Boltzmann-Volterra superposition principle, in terms of real order integrals and derivatives (fractional-order calculus). It is shown that the power laws describing creep/relaxation of bone tissue may be obtained by introducing a fractal description of bone cross-section, and the Hausdorff dimension of the fractal geometry is then related to the exponent of the power law.

The mechanically based non-local elasticity: an overview of main results and future challenges.

The mechanically based non-local elasticity has been used, recently, in wider and wider engineering applications involving small-size devices and/or materials with marked microstructures. The key feature of the model involves the presence of non-local effects as additional body forces acting on material masses and depending on their relative displacements. An overview of the main results of the theory is reported in this paper.