An orthotropic continuum model with substructure evolution for describing bone remodeling: an interpretation of the primary mechanism behind Wolff's law.

We propose a variational approach that employs a generalized principle of virtual work to estimate both the mechanical response and the changes in living bone tissue during the remodeling process. This approach provides an explanation for the adaptive regulation of the bone substructure in the context of orthotropic material symmetry. We specifically focus upon the crucial gradual adjustment of bone tissue as a structural material that adapts its mechanical features, such as materials stiffnesses and microstructure, in response to the evolving loading conditions. We postulate that the evolution process relies on a feedback mechanism involving multiple stimulus signals. The mechanical and remodeling behavior of bone tissue is clearly a complex process that is difficult to describe within the framework of classical continuum theories. For this reason, a generalized continuum elastic theory is employed as a proper mathematical context for an adequate description of the examined phenomenon. To simplify the investigation, we considered a two-dimensional problem. Numerical simulations have been performed to illustrate bone evolution in a few significant cases: the bending of a rectangular cantilever plate and a three-point flexure test. The results are encouraging because they can replicate the optimization process observed in bone remodeling. The proposed model provides a likely distribution of stiffnesses and accurately represents the arrangement of trabeculae macroscopically described by the orthotropic symmetry directions, as supported by experimental evidence from the trajectorial theory.

Dynamic Testing of Lime-Tree (Tilia Europoea) and Pine (Pinaceae) for Wood Model Identification.

The paper presents the results of dynamic testing of two wood species: lime-tree (Tilia europoea) and pine (Pinaceae). The dynamic compressive tests were carried out using the traditional Kolsky method in compression tests. The Kolsky method was modified for testing the specimen in a rigid limiting holder. In the first case, stress-strain diagrams for uniaxial stress state were obtained, while in the second, for uniaxial deformation. To create the load a gas gun was used. According to the results of the experiments, dynamic stress-strain diagrams were obtained. The limiting strength and deformation characteristics were determined. The fracture energy of lime and pine depending on the type of test was also obtained. The strain rates and stress growth rates were determined. The influence of the cutting angle of the specimens relative to the grain was noted. Based on the results obtained, the necessary parameters of the wood model were determined and their adequacy was assessed by using a special verification experiment.

On mechanically driven biological stimulus for bone remodeling as a diffusive phenomenon.

In the past years, many attempts have been made in order to model the process of bone remodeling. This process is complex, as it is governed by not yet completely understood biomechanical coupled phenomena. It is well known that bone tissue is able to self-adapt to different environmental demands of both mechanical and biological origin. The mechanical aspects are related to the functional purpose of the bone tissue, i.e., to provide support to the body and protection for the vitally important organs in response to the external loads. The many biological aspects include the process of oxygen and nutrients supply. To describe the biomechanical process of functional adaptation of bone tissue, the approach commonly adopted is to consider it as a 'feedback' control regulated by the bone cells, namely osteoblasts and osteoclasts. They are responsible for bone synthesis and resorption, respectively, while osteocytes are in charge of 'sensing' the mechanical status of the tissue. Within this framework, in  Lekszycki and dell'Isola (ZAMM - Zeitschrift für Angewandte Mathematik und Mechanik 92(6):426-444, 2012), a model based on a system of integro-differential equations was introduced aiming to predict the evolution of the process of remodeling in surgically reconstructed bones. The main idea in the aforementioned model was to introduce a scalar field, describing the biological stimulus regulating the interaction among all kinds of bone cells at a macroscale. This biological field was assumed to depend locally on certain deformation measures of the (reconstructed) bone tissue. However, biological knowledge suggests that this stimulus, after having been produced, 'diffuses' in bone tissue, so controlling in a complex way its remodeling. This means that the cells which are target of the stimulus may not be located in the same place occupied by the cells producing it. In this paper, we propose a model which intends to explain the diffusive nature of the biological stimulus to encompass the time-dependent and space-time displaced effects involved in bone reconstruction process. Preliminary numerical simulations performed in typical cases are presented. These numerical case studies suggest that the 'diffusive' model of stimulus is promising: we plan to continue these kinds of studies in further investigations.

King post truss as a motif for internal structure of (meta)material with controlled elastic properties.

One of the most interesting challenges in the modern theory of materials consists in the determination of those microstructures which produce, at the macro-level, a class of metamaterials whose elastic range is many orders of magnitude wider than the one exhibited by 'standard' materials. In dell'Isola et al. (2015 Zeitschrift für angewandte Mathematik und Physik66, 3473-3498. (doi:10.1007/s00033-015-0556-4)), it was proved that, with a pantographic microstructure constituted by 'long' micro-beams it is possible to obtain metamaterials whose elastic range spans up to an elongation exceeding 30%. In this paper, we demonstrate that the same behaviour can be obtained by means of an internal microstructure based on a king post motif. This solution shows many advantages: it involves only microbeams; all constituting beams are undergoing only extension or compression; all internal constraints are terminal pivots. While the elastic deformation energy can be determined as easily as in the case of long-beam microstructure, the proposed design seems to have obvious remarkable advantages: it seems to be more damage resistant and therefore to be able to have a wider elastic range; it can be realized with the same three-dimensional printing technology; it seems to be less subject to compression buckling. The analysis which we present here includes: (i) the determination of Hencky-type discrete models for king post trusses, (ii) the application of an effective integration scheme to a class of relevant deformation tests for the proposed metamaterial and (iii) the numerical determination of an equivalent second gradient continuum model. The numerical tools which we have developed and which are presented here can be readily used to develop an extensive measurement campaign for the proposed metamaterial.

A visco-poroelastic model of functional adaptation in bones reconstructed with bio-resorbable materials.

In this paper, the phenomena of resorption and growth of bone tissue and resorption of the biomaterial inside a bicomponent system are studied by means of a numerical method based on finite elements. The material behavior is described by a poro-viscoelastic model with infiltrated voids. The mechanical stimulus that drives these processes is a linear combination of density of strain energy and viscous dissipation. The external excitation is represented by a bending load slowly variable with sinusoidal law characterized by different frequencies. Investigated aspects are the influence of the load frequency, of type of the stimulus and of the effective porosity on the time evolution of the mass densities of considered system.

Cardiac Resynchronization Therapy MOdular REgistry: ECG and Rx predictors of response to cardiac resynchronization therapy (NCT01573091).

AIMS: A variable proportion, up to 30%, of patients who undergo cardiac resynchronization therapy (CRT) do not benefit from treatment. The aim of the Cardiac Resynchronization Therapy MOdular REgistry (CRT MORE) is to determine whether specific electrocardiographic and radiographic parameters can be used to predict clinical and echocardiographic response to CRT. METHODS: The CRT MORE is a prospective, single-arm, multicenter cohort study designed to evaluate the electrocardiographic and radiographic predictors of response to CRT. All study patients receive a pacemaker or implantable defibrillator for CRT delivery in accordance with current guidelines. Enrollment started in December 2011 and is scheduled to end in November 2013. Approximately 1100 consecutive patients will be enrolled in 30 Italian centers and will be followed up for 60 months after implantation. The primary endpoint is the improvement in clinical (Clinical Composite Score) and echocardiographic (a decrease of ≥ 15% in left ventricular end-systolic volume) parameters at the 6-month follow-up visit. CONCLUSION: This study might provide important information about which electrocardiographic and radiographic parameters better predict CRT response.

Impact of transseptal puncture site on acute and mid-term outcomes during cryoballoon ablation: a comparison between anterior, medial and posterior transatrial access.

BACKGROUND: Cryoballoon ablation (CBA) (Arctic Front, Medtronic, USA) has proven very effective in achieving pulmonary vein isolation (PVI). Different transseptal (TS) puncture sites might influence CBA procedure. The aim of the present study was to analyze the influence of different TS puncture sites (anterior, medial and posterior) on the acute and midterm outcomes of CBA in a series of patients undergoing PVI for drug resistant AF. METHODS AND RESULTS: A total 103 patients (78 males, mean age: 57 ± 13 years) formed the study group. Transseptal punctures were performed in the anterior, medial and posterior portion of the FO in 41 (39.8%), 35 (34%) and 27 (26.2%) patients respectively. We found no statistical significant difference between the various sites of TS puncture in 1) the grade of PV occlusion (p = ns), the rate of PV isolation (p = ns), freedom from AF at a mean 12 month follow-up (p = ns) and complication rates (p = ns). Mean grade of occlusion was slightly lower in the RIPV when puncturing in the posterior FO but did not reach statistical significance. Mean procedural and fluoroscopy times were significantly lower when using the inner lumen mapping catheter (ILMC) (Achieve, Medtronic, USA) than the circular mapping catheter (CMC) (Lasso, Biosense Webster, California, USA) (107.24 mn vs 97.74 (p ≤ 0.001) and 25.7 mn vs 19.2 mn (p ≤ 0.001)). CONCLUSION: Different sites of TS puncture on the horizontal axis of the FO (anterior, medial and posterior) did not influence grades of PV occlusion, rates of isolation, mid-term outcome and rates of complications during CB ablation.