Researchers have come together to make improvements in cardiac medicine, releasing the details of a recent study in “Drug response analysis for scaffold-free cardiac constructs fabricated using bio-3D printer.” Acting on previous research which resulted in bioprinted tubular cardiac constructs, the scientists have now continued their work to create a technique for evaluating contractile force and drug response.
While striving to eliminate the need for animal testing or clinical studies, the researchers realize the ongoing requirement to measure the effects of drugs on humans, stating, “understanding the drug response of the heart is essential for new drug development.”
In many cases, testing requires substantial time and expense and can also be detrimental to the health of those participating in studies. Developing cardiac constructs without scaffolds allowed for comprehensive and accurate evaluation of drug response.
Upon creating a contraction analysis system, the authors tested:
- Electrical stimulation
- Temperature dependence of spontaneous contraction in cardiac constructs
- Drug reactivity analysis of cardiac constructs
- Cytotoxicity effect of doxorubicin on cardiac constructs
To monitor the ‘beating rate’ of the cardiac constructs, the researchers established continued assessment of electrical stimulation:
“During the spontaneous contraction condition, the beating rate of cardiac constructs was 3 beats per 10s. When 1 or 2 Hz-paced electrical stimulation was applied to cardiac constructs, the beating rate increased. However, 2Hz paced electrical stimulation prevented full relaxation of the cardiac constructs and showed a decrease in the top movement of the needle. Stevens et al. also demonstrated that scaffold-free cardiac patches showed a decrease in contractile force at 2Hz or 3Hz paced electrical stimulation26. Thus, our results indicate that this contraction analysis system can reproduce the contraction of the human heart.”
Consistency in temperature is required for the cardiac constructs, with variations affecting the beating rate—leaving the researchers to note that such control is a ‘very important parameter’ in such testing. Moving forward in the study, four drugs were used during experimentation: isoproterenol, propranolol, blebbistatin, and doxorubicin.
“We selected well-known drugs, isoproterenol and propranolol, because of their ability to change the beating rate and contractile force of cardiomyocytes,” said the authors.
Because evaluating the dangers of cardiotoxicity was critical in the study, the researchers focused on doxorubicin (DOX) as a ‘model drug’ for such an assessment. The results were in line with other studies, indicating that the beating rate did not vary at one hour after the application of DOX. Overall, all factors showed that cardiotoxicity could be monitored with the new system and follow-up analysis.
“We could not calculate the contractile force of the construct, because the length of needle array was not uniform at the micro-level,” concluded the researchers. “In future, we will evaluate the contractile force accurately by improving the length of the needle array. Second, we used the frame rate (30 frames per s) of our video camera to evaluate contraction of the cardiac constructs. Conversely, Takeda et al. reported that a video camera recording at 150 frames per s can measure the contraction velocity of cardiomyocytes as well as the relaxation velocity and contraction-relaxation velocity. Tus, in the future, we aim to perform contraction analysis of cardiac constructs using a video camera with a high frame rate.
“This analysis method can be used for new drug development, due to its high drug response predictability in vitro. We believe that accuracy of this contraction analysis system will increase in the future due to advances in camera technology and the quality of the needle array.”
Scientists, manufacturers, engineers, and a variety of users around the globe continue to shed constraints that cause challenge or extra steps in digital fabrication—from industrial applications in aerospace, automotive, and construction, to bioprinting, where refining the process could be critical to the ultimate goal of being able to fabricate amazing items like human organs
What do you think of this news? Let us know your thoughts! Join the discussion of this and other 3D printing topics at 3DPrintBoard.com.[Source / Images: ‘Drug response analysis for scaffold-free cardiac constructs fabricated using bio-3D printer’]
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