Key result
Antioxidants mitigate doxorubicin-induced toxicity in 3D bioprinted spheroids, preventing an absolute ~75% loss in cardiomyocyte viability.
3D spheroids validate high-throughput doxorubicin cardiotoxicity testing; leaves open clinical translation of NAC or Tiron cardioprotection.
1.02 ± 0.28% viable cells in 2D cultures, after 5 days of culture. Moreover, a flow cytometric analysis study was conducted to study CMs proliferation in the presence of DOX and antioxidants. Our data support the use of a 3D bioprinted cardiac spheroidal droplet as a robust and high-throughput screening model for drug toxicity. In the future, this 3D spheroidal droplet model can be adopted as a human-derived tissue-engineered equivalent to address challenges in other various aspects of biomedical pre-clinical research.
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Khoury et al. (2023) studied Doxorubicin-induced cardiotoxicity. Doxorubicin with or without antioxidants (N-acetyl cysteine [NAC] and Tiron) vs. 2D cell culture controls and untreated (no doxorubicin) 3D spheroidal droplets was evaluated on Cardiomyocyte cell viability (% CV) at day 5 in 3D bioprinted spheroidal droplets exposed to 1 μM doxorubicin (p=0.015). Doxorubicin (1 μM) reduced cardiomyocyte viability in 3D bioprinted spheroids from 75% to 0.22% over 5 days (p=0.015), which was mitigated by 15 mM NAC (95% viability) or Tiron (92% viability).
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