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Electrical stimulation (ES) highly influences the cellular microenvironment, affecting cell migration, proliferation and differentiation. It also plays a crucial role in tissue engineering to improve the biomechanical properties of the constructs and regenerate the damaged tissues. However, the effects of the ES on the neuromuscular junction (NMJ) are still not fully analyzed. In this context, the development of a specialized microfluidic device combined with an ad-hoc electrical stimulation can allow a better investigation of the NMJ functionality. To this aim, we performed an analysis of the electric field distribution in a 3D neuromuscular junction microfluidic device for the design of several electrode systems. At first, we designed and modeled the 3D microfluidic device in order to promote the formation of the NMJ between neuronal cells and the muscle engineered tissue. Subsequently, with the aim of identifying the optimal electrode configuration able to properly stimulate the neurites, thus enhancing the formation of the NMJ, we performed different simulation tests of the electric field distribution, by varying the electrode type, size, position and applied voltage. Our results revealed that all the tested configurations did not induce an electric field dangerous for the cell vitality. Among these configurations, the one with cylindrical pin of 0.3 mm of radius, placed in the internal position of the neuronal chambers, allowed to obtain the highest electrical field in the zone comprising the neurites.

Skeletal muscle fatigue is most often studied as a response to repeated stimulations in isometric conditions and it is usually quantified as the progressive loss of force generating capability over time. However, physical dynamic activity is based on the shortening of skeletal muscles. Therefore, the condition that best mimics body movements is the isotonic one, in which muscle is allowed to shorten against a constant load. In the literature, the isotonic fatigue test is performed allowing the muscle to lift a load corresponding to one-third of the maximal isometric force (reference optimal force), as best representative of the force at which the tissue develops its maximum power. The goal of this study was to devise a new testing protocol in which each muscle was tested for isotonic fatigue by shortening against its own optimal force, i.e. the force at which it really developed the maximum power. Our hypothesis was that testing all the muscle at a standard reference value would introduce significant errors in the parameters associated to muscle fatigue and in their variance. The proposed protocol was based on the real-time measurement of the maximum power a muscle was able to generate through the application of the after-load technique and a mathematical interpolation to the Hill's equation, that therefore allowed to determine the experimental optimal force to be applied during the fatigue test. Experimental results showed that the muscles tested with the experimental optimal force had a fatigue time significantly lower than the control muscles tested with the reference optimal force. A decrease, even if not statistically significant, was also measured for the power and work generated during the fatigue test. Of note, for all these parameters a huge decrease in the measurement variance was reported, confirming that a precise assessment of the muscle experimental optimal force was needed to increase the accuracy of the measurements. On the other hand, the application of the protocol proposed in this work required an increase in the test duration, due to the application of the after-load technique, and a real time measurement of the power generated by the tissue.

The hepatitis B virus (HBV) infection represents a global health problem; it can be transmitted through contact with infected blood or other body fluids and it is dangerous being highly contagious. Hepatitis B is preventable with effective vaccine, as it is strongly recommended by the World Health Organization; its protection is possibly life-long, at least 20 years. Mathematical modelling is a useful tool to study the evolution of an epidemic spread and possibly to suggest suitable control strategies, aiming at the best resource allocation while satisfying the obvious limitations, both from economics and practical points of view. In this paper, a recently proposed model describing the HBV infection is adopted and optimal control strategies are discussed; it is enhanced the dependence of the result on the preliminary choice of the cost index, suggesting a rationale in the determination of the weights of the elements to be minimized.