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Dynamic culture of bioprinted liver tumor spheroids in a pillar/perfusion plate for predictive screening of anticancer drugs
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  • Pranav Joshi,
  • Hamilton Silva do Nascimento,
  • Soo-Yeon Kang,
  • Minseong Lee,
  • Manav Goud Vanga,
  • Sang-Hyun Lee,
  • Bosung Ku,
  • Moyses dos Santos Miranda,
  • Moo-Yeal Lee
Pranav Joshi
Bioprinting Laboratories Inc
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Hamilton Silva do Nascimento
University of North Texas
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Soo-Yeon Kang
University of North Texas
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Minseong Lee
University of North Texas
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Manav Goud Vanga
Bioprinting Laboratories Inc
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Sang-Hyun Lee
MBD Co Ltd
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Bosung Ku
MBD Co Ltd
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Moyses dos Santos Miranda
Universidade Federal do Para - Campus Castanhal
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Moo-Yeal Lee
Bioprinting Laboratories Inc

Corresponding Author:[email protected]

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Abstract

Recent advancements in three-dimensional (3D) cell culture technologies, such as cell spheroids, organoids, and 3D bioprinted tissue constructs, have significantly improved the physiological relevance of in vitro models. These models better mimic tissue structure and function, closely emulating in vivo characteristics and enhancing phenotypic analysis, critical for basic research and drug screening in personalized cancer therapy. Despite their potential, current 3D cell culture platforms face technical challenges, which include user unfriendliness in long-term dynamic cell culture, incompatibility with rapid cell encapsulation in biomimetic hydrogels, and low throughput for compound screening. To address these issues, we developed a 144-pillar plate with sidewalls and slits (144PillarPlate) and a complementary 144-perfusion plate with perfusion wells and reservoirs (144PerfusionPlate) for dynamic 3D cell culture and predictive compound screening. To accelerate biomimetic tissue formation, small Hep3B liver tumor spheroids suspended in alginate were printed and encapsulated on the 144PillarPlate rapidly by using microsolenoid valve-driven 3D bioprinting technology. The microarray bioprinting technology enabled precise and rapid loading of small spheroids in alginate on the pillar plate, facilitating reproducible and scalable formation of large tumor spheroids with minimal manual intervention. The bioprinted Hep3B spheroids on the 144PillarPlate were dynamically cultured in the 144PerfusionPlate and tested with anticancer drugs to measure drug effectiveness and determine the concentration required to inhibit 50% of the cell viability (IC 50 value). The perfusion plate enabled the convenient dynamic culture of tumor spheroids and facilitated the dynamic testing of anticancer drugs with increased sensitivity. It is envisioned that the integration of microarray bioprinting of tumor spheroids onto the pillar plate, along with dynamic 3D cell culture in the perfusion plate, could more accurately replicate tumor microenvironments. This advancement has the potential to enhance the predictive drug screening process in personalized cancer therapy significantly.
28 Aug 2024Submitted to Biotechnology and Bioengineering
30 Aug 2024Submission Checks Completed
30 Aug 2024Assigned to Editor
30 Aug 2024Review(s) Completed, Editorial Evaluation Pending
02 Sep 2024Reviewer(s) Assigned