Competing mechanisms of stress-assisted diffusivity and stretch-activated currents in cardiac electromechanics

We numerically investigate the role of mechanical stress in modifying the conductivity properties of the cardiac tissue and its impact in computational models for cardiac electromechanics. We follow a theoretical framework recently proposed in [Cherubini, Filippi, Gizzi, Ruiz-Baier, JTB 2017], in the context of general reaction-diffusion-mechanics systems using multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling using computational tests, conducted using a finite element method. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications

Multilevel synchronization of human β-cells networks

β-cells within the endocrine pancreas are fundamental for glucose, lipid and protein homeostasis. Gap junctions between cells constitute the primary coupling mechanism through which cells synchronize their electrical and metabolic activities. This evidence is still only partially investigated through models and numerical simulations. In this contribution, we explore the effect of combined electrical and metabolic coupling in β-cell clusters using a detailed biophysical model. We add heterogeneity and stochasticity to realistically reproduce β-cell dynamics and study networks mimicking arrangements of β-cells within human pancreatic islets. Model simulations are performed over different couplings and heterogeneities, analyzing emerging synchronization at the membrane potential, calcium, and metabolites levels. To describe network synchronization, we use the formalism of multiplex networks and investigate functional network properties and multiplex synchronization motifs over the structural, electrical, and metabolic layers. Our results show that metabolic coupling can support slow wave propagation in human islets, that combined electrical and metabolic synchronization is realized in small aggregates, and that metabolic long-range correlation is more pronounced with respect to the electrical one

Nonlinear diffusion & thermo-electric coupling in a two-variable model of cardiac action potential

This work reports the results of the theoretical investigation of nonlinear dynamics and spiral wave breakup in a generalized two-variable model of cardiac action potential accounting for thermo-electric coupling and diffusion nonlinearities. As customary in excitable media, the common Q10 and Moore factors are used to describe thermo-electric feedback in a 10-degrees range. Motivated by the porous nature of the cardiac tissue, in this study we also propose a nonlinear Fickian flux formulated by Taylor expanding the voltage dependent diffusion coefficient up to quadratic terms. A fine tuning of the diffusive parameters is performed a priori to match the conduction velocity of the equivalent cable model. The resulting combined effects are then studied by numerically simulating different stimulation protocols on a one-dimensional cable. Model features are compared in terms of action potential morphology, restitution curves, frequency spectra and spatio-temporal phase differences. Two-dimensional long-run simulations are finally performed to characterize spiral breakup during sustained fibrillation at different thermal states. Temperature and nonlinear diffusion effects are found to impact the repolarization phase of the action potential wave with non-monotone patterns and to increase the propensity of arrhythmogenesis

Tissue Engineering for Rotator Cuff Repair: An Evidence-Based Systematic Review

The purpose of this systematic review was to address the treatment of rotator cuff tears by applying tissue engineering approaches to improve tendon healing, specifically platelet rich plasma (PRP) augmentation, stem cells, and scaffolds. Our systematic search was performed using the combination of the following terms: “rotator cuff”, “shoulder”, “PRP”, “platelet rich plasma”, “stemcells”, “scaffold”, “growth factors”, and “tissue engineering”. No level I or II studies were found on the use of scaffolds and stem cells for rotator cuff repair. Three studies compared rotator cuff repair with or without PRP augmentation. All authors performed arthroscopic rotator cuff repair with different techniques of suture anchor fixation and different PRP augmentation. The three studies found no difference in clinical rating scales and functional outcomes between PRP and control groups. Only one study showed clinical statistically significant difference between the two groups at the 3-month follow up. Any statistically significant difference in the rates of tendon rerupture between the control group and the PRP group was found using the magnetic resonance imaging. The current literature on tissue engineering application for rotator cuff repair is scanty. Comparative studies included in this review suggest that PRP augmented repair of a rotator cuff does not yield improved functional and clinical outcome compared with non-augmented repair at a medium and long-term followup

Tissue Engineered Strategies for Skeletal Muscle Injury

Skeletal muscle injuries are common in athletes, occurring with direct and indirect mechanisms and marked residual effects, such as severe long-term pain and physical disability. Current therapy consists of conservative management including RICE protocol (rest, ice, compression and elevation), nonsteroidal anti-inflammatory drugs, and intramuscular corticosteroids. However, current management of muscle injuries often does not provide optimal restoration to preinjury status. New biological therapies, such as injection of platelet-rich plasma and stem-cell-based therapy, are appealing. Although some studies support PRP application in muscle-injury management, reasons for concern persist, and further research is required for a standardized and safe use of PRP in clinical practice. The role of stem cells needs to be confirmed, as studies are still limited and inconsistent. Further research is needed to identify mechanisms involved in muscle regeneration and in survival, proliferation, and differentiation of stem cells