Matrigel 3D bioprinting of contractile human skeletal muscle models recapitulating exercise and pharmacological responses.

A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering of 3D human skeletal muscle models in microplates and functional compound screening to address the lack of muscle wasting disease medication. To this end, we adapted our recently described 24-well plate 3D bioprinting platform with a printhead cooling system to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. Mini skeletal muscle models develop within a week exhibiting contractile, striated myofibers aligned between two attachment posts. As an in vitro exercise model, repeated high impact stimulation of contractions for 3 h by a custom-made electrical pulse stimulation (EPS) system for 24-well plates induced interleukin-6 myokine expression and Akt hypertrophy pathway activation. Furthermore, the known muscle stimulators caffeine and Tirasemtiv acutely increase EPS-induced contractile force of the models. This validated new human muscle MPS will benefit development of drugs against muscle wasting diseases. Moreover, our Matrigel 3D bioprinting platform will allow engineering of non-self-organizing complex human 3D MPS.

Modeling subjective well-being in individuals with chronic pain and a physical disability: the role of pain control and pain catastrophizing.

PURPOSE: To investigate the associations between subjective well-being and pain intensity, pain interference, and depression in individuals with physical disabilities. We hypothesized that (1) pain control and (2) pain catastrophizing mediate the effects of subjective well-being on pain intensity, pain interference, and depression. METHODS: Analyses of cross-sectional data from 96 individuals diagnosed with spinal cord injury, multiple sclerosis, neuromuscular disease, or post-polio syndrome, with average pain intensity of ≥4 (0-10) on at least half the days in the past month. Two models tested study hypotheses using structural equation. RESULTS: Both models showed acceptable model fit. Pain catastrophizing significantly mediated the effect of subjective well-being on pain intensity and pain interference, but not on depression. Pain control did not significantly mediate the effect of subjective well-being on pain intensity, pain interference, or depression. Path coefficients showed significant direct effects of subjective well-being on pain control (ß = 0.39), pain catastrophizing (ß = -0.61), pain interference (ß = -0.48; -0.42), and depression (ß = -0.75; -0.78). CONCLUSIONS: This study supports the potential of enhancing subjective well-being and lowering pain catastrophizing for reducing pain intensity, pain interference, and depressive symptoms in individuals with chronic pain and a physical disability. The findings indicate that true experiments to test for causal associations are warranted. Implications for rehabilitation The majority of individuals with physical disabilities report having persistent moderate-to-severe pain that may negatively limit daily activities and quality of life. The present cross-sectional study indicates that individuals who reported greater subjective well-being showed significantly lower pain intensity via the mediating effect of lower pain catastrophizing. Since sample size and respective power are low, these findings should be taken as first indications of potential underlying mechanisms between subjective well-being and pain outcomes that need further confirmation in longitudinal research. However, the findings suggest that treatments which enhance subjective well-being (increasing positive affect and life satisfaction, and decreasing negative affect, e.g., via positive psychology exercises) and reducing pain catastrophizing (via e.g., cognitive-behavioral therapy) may have the highest potential for benefiting individuals with disability-associated chronic pain.

The influence of heat treatment and plastic deformation on the bio-degradation of a Mg-Y-RE alloy.

In this study the bio-degradation behavior of a Mg-Y-RE alloy in different heat treatment states with respect to the alloy's potential application as biodegradable implant material was investigated by electrochemical impedance spectroscopy in two body-similar fluids. The heat treatments increase the degradation resistance of the alloy and lead to the formation of a thermal oxide layer on the sample surface and to a change in microstructure such as the distribution of yttrium. The varying Y distribution in the alloy does not significantly influence the degradation behavior, and all samples show a similar low polarization resistance. However, samples with a thermal oxide layer, which consists mainly of Y(2)O(3), degrade much more slowly and feature remarkably high polarization resistance. Nevertheless, in some cases localized corrosion attack occurs and drastically impairs performance. Cracks in the oxide layer, intentionally induced by straining of the samples and which in practice could originate from the implantation process, reduce the corrosion resistance. However, these samples perform still better than polished specimens and show a macroscopically homogeneous degradation behavior without localized corrosion. Microscopically, corrosion attacks start at the cracks and undermining of the oxide layer occurs with time. For all the material conditions a remarkable dependence of the degradation rate on the electrolyte is noted.