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The forces that allow body movement can be divided into active (generated by sarcomeric contractile proteins) and passive (sustained by intra-sarcomeric proteins, fibre cytoskeleton and extracellular matrix (ECM)). These are needed to transmit the active forces to the tendon and the skeleton. However, the relative contribution of the intra- and extra- sarcomeric components in transmitting the passive forces is still under debate. There is limited data in the literature about human muscle and so it is difficult to make predictions using multiscale models, imposing a purely phenomenological description for passive forces. In this paper, we apply a method for the experimental characterization of the passive properties of fibres and ECM to human biopsy and propose their clear separation in a Finite Element Model. Experimental data were collected on human single muscle fibres and bundles, taken from vastus lateralis muscle of elderly subjects. Both were progressively elongated to obtain two stress-strain curves which were fitted to exponential equations. The mechanical properties of the extracellular passive components in a bundle of fibres were deduced by the subtraction of the passive tension observed in single fibres from the passive tension observed in the bundle itself. Our results showed that modulus and tensile load bearing capability of ECM are higher than those of fibres and defined their quantitative characterization that can be used in macroscopic models to study their role in the transmission of forces in physiological and pathophysiological conditions.

Engineered skeletal muscle tissues have been proposed as potential solutions for volumetric muscle losses, and biologic scaffolds have been obtained by decellularization of animal skeletal muscles. The aim of the present work was to analyse the characteristics of a biologic scaffold obtained by decellularization of human skeletal muscles (also through comparison with rats and rabbits) and to evaluate its integration capability in a rabbit model with an abdominal wall defect. Rat, rabbit and human muscle samples were alternatively decellularized with two protocols: n.1, involving sodium deoxycholate and DNase I; n.2, trypsin-EDTA and Triton X-NH4OH. Protocol 2 proved more effective, removing all cellular material and maintaining the three-dimensional networks of collagen and elastic fibers. Ultrastructural analyses with transmission and scanning electron microscopy confirmed the preservation of collagen, elastic fibres, glycosaminoglycans and proteoglycans. Implantation of human scaffolds in rabbits gave good results in terms of integration, although recellularization by muscle cells was not completely achieved. In conclusion, human skeletal muscles may be effectively decellularized to obtain scaffolds preserving the architecture of the extracellular matrix and showing mechanical properties suitable for implantation/integration. Further analyses will be necessary to verify the suitability of these scaffolds for in vitro recolonization by autologous cells before in vivo implantation.

This study explores the effectiveness of architected lattice structures, specifically made of polyamide 12 (PA12) material, as potential helmet liners to mitigate traumatic brain injuries (TBI), with a focus on rotational acceleration. Evaluating three lattice unit cell topologies (simple cubic, dode-medium, and rhombic dodecahedron), the research builds upon prior investigations indicating that PA12 lattice liners may outperform conventional EPS liners. Employing a high-fidelity finite element male head model and utilizing direct and oblique impact scenarios, mechanical quantities, such as maximum principal strain (MPS) and shear strain, cumulative strain damage measure and intracranial pressure were measured at the tissue level in different brain regions. Results indicate that lattice liners, especially with dode-medium topology, exhibit promising reductions in brain tissue strains. On average, during oblique impacts, less than 1 % of the brain volume experienced an MPS level of 0.4 when the lattice liners were adopted, whereas that percentage was above 70 % with the expandable polystyrene (EPS) foam liners. Pressure-based assessments suggest that lattice liners may outperform EPS liners in oblique impacts, showcasing the limitations of EPS for effective TBI mitigation. Despite certain model limitations, this study emphasizes the need for advancements in helmet technology, particularly in the development of commercial lattice liners using additive manufacturing, to address the limitations of existing EPS liners in preventing rotational consequences of impacts and reducing TBI.

Morphogenesis requires embryonic cells to generate forces and perform mechanical work to shape their tissues. Incorrect functioning of these force fields can lead to congenital malformations. Understanding these dynamic processes requires the quantification and profiling of three-dimensional mechanics during evolving vertebrate morphogenesis. Here we describe elastic spring-like force sensors with micrometre-level resolution, fabricated by intravital three-dimensional bioprinting directly in the closing neural tubes of growing chicken embryos. Integration of calibrated sensor read-outs with computational mechanical modelling allows direct quantification of the forces and work performed by the embryonic tissues. As they displace towards the embryonic midline, the two halves of the closing neural tube reach a compression of over a hundred nano-newtons during neural fold apposition. Pharmacological inhibition of Rho-associated kinase to decrease the pro-closure force shows the existence of active anti-closure forces, which progressively widen the neural tube and must be overcome to achieve neural tube closure. Overall, our approach and findings highlight the intricate interplay between mechanical forces and tissue morphogenesis. Hydrogel force sensors directly bioprinted into embryonic tissues quantify the forces driving tissue remodelling and reveal the existence of mechanisms that counteract tissue morphogenesis.

Aging of human skeletal muscles is associated with increased passive stiffness, but it is still debated whether muscle fibers or extracellular matrix (ECM) are the determinants of such change. To answer this question, we compared the passive stress generated by elongation of fibers alone and arranged in small bundles in young healthy (Y: 21 years) and elderly (E: 67 years) subjects. The physiological range of sarcomere length (SL) 2.5–3.3 μm was explored. The area of ECM between muscle fibers was determined on transversal sections with picrosirius red, a staining specific for collagen fibers. The passive tension of fiber bundles was significantly higher in E compared to Y at all SL. However, the resistance to elongation of fibers alone was not different between the two groups, while the ECM contribution was significantly increased in E compared to Y. The proportion of muscle area occupied by ECM increased from 3.3% in Y to 8.2% in E. When the contribution of ECM to bundle tension was normalized to the fraction of area occupied by ECM, the difference disappeared. We conclude that, in human skeletal muscles, the age-related reduced compliance is due to an increased stiffness of ECM, mainly caused by collagen accumulation.

Deep fascia has long been considered a source of pain, secondary to nerve pain receptors becoming enmeshed within the pathological changes to which fascia are subject. Densification and fibrosis are among such changes. They can modify the mechanical properties of deep fasciae and damage the function of underlying muscles or organs. Distinguishing between these two different changes in fascia, and understanding the connective tissue matrix within fascia, together with the mechanical forces involved, will make it possible to assign more specific treatment modalities to relieve chronic pain syndromes. This review provides an overall description of deep fasciae and the mechanical properties in order to identify the various alterations that can lead to pain. Diet, exercise, and overuse syndromes are able to modify the viscosity of loose connective tissue within fascia, causing densification, an alteration that is easily reversible. Trauma, surgery, diabetes, and aging alter the fibrous layers of fasciae, leading to fascial fibrosis.

Three-dimensional bioprinting is the process of manipulating cell-laden bioinks to fabricate living structures. Three-dimensional bioprinting techniques have brought considerable innovation in biomedicine, especially in the field of tissue engineering, allowing the production of 3D organ and tissue models for in vivo transplantation purposes or for in-depth and precise in vitro analyses. Naturally derived hydrogels, especially those obtained from the decellularization of biological tissues, are promising bioinks for 3D printing purposes, as they present the best biocompatibility characteristics. Despite this, many natural hydrogels do not possess the necessary mechanical properties to allow a simple and immediate application in the 3D printing process. In this review, we focus on the bioactive and mechanical characteristics that natural hydrogels may possess to allow efficient production of organs and tissues for biomedical applications, emphasizing the reinforcement techniques to improve their biomechanical properties.

The evaluation of the biomechanics of the abdominal wall is particularly important to understand the onset of pathological conditions related to weakening and injury of the abdominal muscles. A better understanding of the biomechanics of the abdominal wall could be a breakthrough in the development of new therapeutic approaches. For this purpose, several studies in the literature propose finite element models of the human abdomen, based on the geometry of the abdominal wall from medical images and on constitutive formulations describing the mechanical behavior of fascial and muscular tissues. The biomechanics of the abdominal wall depends on the passive mechanical properties of fascial and muscle tissue, on the activation of abdominal muscles, and on the variable intra-abdominal pressure. To assess the quantitative contribution of these features to the development and validation of reliable numerical models, experimental data are fundamental. This work presents a review of the state of the art of numerical models developed to investigate abdominal wall biomechanics. Different experimental techniques, which can provide data for model validation, are also presented. These include electromyography, ultrasound imaging, intraabdominal pressure measurements, abdominal surface deformation, and stiffness/compliance measurements.

Muscles exhibit highly complex, multi-scale architecture with thousands of muscle fibers, each with different properties, interacting with each other and surrounding connective structures. Consequently, the results of single-fiber experiments are scarcely linked to the macroscopic or whole muscle behavior. This is especially true for human muscles where it would be important to understand of how skeletal muscles disorders affect patients’ life. In this work, we developed a mathematical model to study how fast and slow muscle fibers, well characterized in single-fiber experiments, work and generate together force and displacement in muscle bundles. We characterized the parameters of a Hill-type model, using experimental data on fast and slow single human muscle fibers, and comparing experimental data with numerical simulations obtained from finite element (FE) models of single fibers. Then, we developed a FE model of a bundle of 19 fibers, based on an immunohistochemically stained cross section of human diaphragm and including the corresponding properties of each slow or fast fiber. Simulations of isotonic contractions of the bundle model allowed the generation of its apparent force–velocity relationship. Although close to the average of the force–velocity curves of fast and slow fibers, the bundle curve deviates substantially toward the fast fibers at low loads. We believe that the present model and the characterization of the force–velocity curve of a fiber bundle represents the starting point to link the single-fiber properties to those of whole muscle with FE application in phenomenological models of human muscles.

Three-dimensional (3D) bioprinting has become a widely exploited tissue engineering technique for producing functional constructs that can mimic and replace native tissues. To this end, different printing strategies can be adopted, including inkjet-based, light-assisted, and extrusion-based bioprinting. Despite the great improvements that these innovative techniques introduce, cell viability maintenance during and after the bioprinting process remains a challenging open question. Indeed, the reduction in cell viability is generally related to several crucial conditions during printing, such as high shear stresses and a nutrient-deficient environment of printed constructs. In this work, the current literature on 3D bioprinting technologies is reviewed, focusing on the level of cell damage that can be imparted during biomaterial printing. In particular, extrusion bioprinting, extrusion-associated shear stress and its impact on cell viability are described in detail. The simulation of the bioprinting process through computational fluid dynamics is proposed as an appropriate method to analyze the parameters involved during bioprinting. Moreover, the viability of cells encapsulated into bioink is discussed, as well as literature techniques aimed at enhancing it by both biomaterial modifications and cell micro-encapsulation.