Quantification of the Oxygen Consumption Capabilities of Human, Tissue-Engineered Myobundles under Perfusion and Simulated Exercise

Abstract

<p>Advances in tissue engineering have led to the development of 3D biomimetic models of human skeletal muscle (myobundles), which have the potential to serve as surrogates for animals in drug trials and even implanted into those who have lost skeletal muscle due to muscle wasting disorders1,2. Much work has been done characterizing myobundle functional responses such as contractile force2. However, oxygen consumption of these myobundles is one key functional metric that needs to be investigated, in order to fully characterize them and determine if they can be used as reliable models. Not only that, investigating myobundle oxygen consumption also provides insight into their metabolic pathways, such as oxidative phosphorylation3. In order to accomplish this, we created a novel perfusion system incorporating optical oxygen sensors in order to quantify respiration of myobundles. In addition, a computational model of the system and comparisons with a commercial respiration measurement system (O2K OROBOROS) were used in order to validate the results. The perfusion system was also modified to enable electrical stimulation of the myobundles in order to measure the basal rate of respiration under simulated exercise, Results from these experiments show that the perfusion system accurately quantifies the basal respiration rate, as demonstrated by agreement between the experimental results and the comparisons with the O2K system and the theoretical model. In addition, stimulation of the myobundles lead to increases in respiration, which matches in vivo muscle behavior under exercise. Exercise respiration values were on average, slightly over 2 times the basal respiration values. In summary, we have created a working perfusion system for non-invasively measuring oxygen consumption of myobundles in situ, under basal and simulated exercise conditions.</p>