Variable Impedance Actuators (VIA) have received increasing attention in recent years as many novel applications involving interactions with an unknown and dynamic environment including humans require actuators with dynamics that are not well-achieved by classical stiff actuators. This paper presents an overview of the different VIAs developed and proposes a classification based on the principles through which the variable stiffness and damping are achieved. The main classes are active impedance by control, inherent compliance and damping actuators, inertial actuators, and combinations of them, which are then further divided into subclasses. This classification allows for designers of new devices to orientate and take inspiration and users of VIA's to be guided in the design and implementation process for their targeted application.

Variable stiffness actuators (VSAs) are complex mechatronic devices that are developed to build passively compliant, robust, and dexterous robots. Numerous different hardware designs have been developed in the past two decades to address various demands on their functionality. This review paper gives a guide to the design process from the analysis of the desired tasks identifying the relevant attributes and their influence on the selection of different components such as motors, sensors, and springs. The influence on the performance of different principles to generate the passive compliance and the variation of the stiffness are investigated. Furthermore, the design contradictions during the engineering process are explained in order to find the best suiting solution for the given purpose. With this in mind, the topics of output power, potential energy capacity, stiffness range, efficiency, and accuracy are discussed. Finally, the dependencies of control, models, sensor setup, and sensor quality are addressed

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Numerous prosthetic feet are currently on the market for individuals with a transtibial amputation, each device aimed at raising the 3C-level (control, comfort and cosmetics) with slightly different characteristics. In general, prosthetic feet can be classified into three categories. These are, following the time line: conventional feet (CF), energy-storing-and-returning (ESR) feet and the recent so-called 'bionic' feet. Researchers have shown enhanced performance properties of ESR feet compared with early CF. However, even with the advanced technology, none of the ESR feet is capable of significantly reducing energy cost of walking or enhancing prosthetic gait (Nielsen et al. J Prosthet Orthotics 1989;1:24-31; Waters et al. J Bone Joint Surg Am 1976;58:42-46; Torburn et al. J Rehabil Res Dev 1990;27:369-384). From the 1990s, gradually more attention has been paid to the incorporation of active elements in prosthetic feet as the passive devices are not capable of providing the individual with sufficient ankle power during gait. Most part of the 'bionic' devices are still on the research level nowadays but one can expect that they will become available on the market soon. In this article, the evolution of prosthetic feet over the last two decades is reflected. The importance of mimicking human ankle-foot biomechanics with prosthetic feet is briefly discussed. Prior work in both objective and subjective evaluation of prosthetic gait is reported.

Exploiting natural dynamics for bipedal locomotion, or passive walking, is gaining interest because of its energy efficiency. However, the natural trajectories of a passive walker are fixed during the design, thus limiting its mobility. A possible solution to this problem is creating a "semi-passive walker" equipped with actuators with adaptable compliance, which allows the natural dynamics to be changed according to the situation. This paper proposes a compliance controller, a strategy for continuously changing the compliance in such a way as to adapt the natural motion of the system to a desired trajectory. This opens up the possibility of following a range of different trajectories with a relatively low energy consumption. The idea is to fit the controllable actuator compliance to the "natural" compliance of the desired trajectory, and combine that with trajectory tracking control. This strategy was implemented and tested on a 1-DOF pendulum setup actuated by an antagonistic pair of pleated pneumatic artificial muscles. Both simulations and measurements show that the proposed strategy for choosing actuator compliance can significantly reduce the amount of control activity and energy consumption without harming tracking precision.

Since their introduction in the early years of this century, variable stiffness actuators (VSA) witnessed a sustained growth of interest in the research community, as shown by the growing number of publications. While many consider VSA very interesting for applications, one of the factors hindering their further diffusion is the relatively new conceptual structure of this technology. When choosing a VSA for their application, educated practitioners, who are used to choosing robot actuators based on standardized procedures and uniformly presented data, would be confronted with an inhomogeneous and rather disorganized mass of information coming mostly from scientific publications. In this paper, the authors consider how the design procedures and data presentation of a generic VSA could be organized so as to minimize the engineer's effort in choosing the actuator type and size that would best fit the application needs. The reader is led through the list of the most important parameters that will determine the ultimate performance of their VSA robot, and influence both the mechanical design and the controller shape. This set of parameters extends the description of a traditional electric actuator with quantities describing the capability of the VSA to change its output stiffness. As an instrument for the enduser, the VSA datasheet is intended to be a compact, self-contained description of an actuator that summarizes all of the salient characteristics that the user must be aware of when choosing a device for their application. At the end some examples of compiled VSA datasheets are reported, as well as a few examples of actuator selection procedures.

Interactions between chronic lymphocytic leukemia (CLL) B cells and the bone marrow (BM) microenvironment play a major function in the physiopathology of CLL. Extracellular vesicles (EVs), which are composed of exosomes and microparticles, play an important role in cell communication. However, little is known about their role in CLL / microenvironment interactions. In the present study, EVs purified by ultracentrifugation from BM mesenchymal stromal cell (BM-MSC) cultures were added to CLL B cells. After their integration into CLL B cells, we observed a decrease of leukemic cell spontaneous apoptosis and an increase in their chemoresistance to several drugs, including fludarabine, ibrutinib, idelalisib and venetoclax after 24 hours. Spontaneous (P=0.0078) and stromal cell-derived factor 1α -induced migration capacities of CLL B cells were also enhanced (P=0.0020). A microarray study highlighted 805 differentially expressed genes between leukemic cells cultured with or without EVs. Of these, genes involved in the B-cell receptor pathway such as CCL3/4, EGR1/2/3, and MYC were increased. Interestingly, this signature presents important overlaps with other microenvironment stimuli such as B-cell receptor stimulation, CLL/nurse-like cells co-culture or those provided by a lymph node microenvironment. Finally, we showed that EVs from MSCs of leukemic patients also rescue leukemic cells from spontaneous or drug-induced apoptosis. However, they induce a higher migration and also a stronger gene modification compared to EVs of healthy MSCs. In conclusion, we show that EVs play a crucial role in CLL B cells/BM microenvironment communication.

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