Enhanced oxygen permeability in membrane-bottomed concave microwells for the formation of pancreatic islet spheroids

Geon Hui Lee, Yesl Jun, Hee Yeong Jang, Junghyo Yoon, Jae Seo Lee, Min Hyung Hong, Seok Chung, Dong Hwee Kim, Sang Hoon Lee

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Oxygen availability is a critical factor in regulating cell viability that ultimately contributes to the normal morphogenesis and functionality of human tissues. Among various cell culture platforms, construction of 3D multicellular spheroids based on microwell arrays has been extensively applied to reconstitute in vitro human tissue models due to its precise control of tissue culture conditions as well as simple fabrication processes. However, an adequate supply of oxygen into the spheroidal cellular aggregation still remains one of the main challenges to producing healthy in vitro spheroidal tissue models. Here, we present a novel design for controlling the oxygen distribution in concave microwell arrays. We show that oxygen permeability into the microwell is tightly regulated by varying the poly-dimethylsiloxane (PDMS) bottom thickness of the concave microwells. Moreover, we validate the enhanced performance of the engineered microwell arrays by culturing non-proliferated primary rat pancreatic islet spheroids on varying bottom thickness from 10 μm to 1050 μm. Morphological and functional analyses performed on the pancreatic islet spheroids grown for 14 days prove the long-term stability, enhanced viability, and increased hormone secretion under the sufficient oxygen delivery conditions. We expect our results could provide knowledge on oxygen distribution in 3-dimensional spheroidal cell structures and critical design concept for tissue engineering applications. Statement of Significance In this study, we present a noble design to control the oxygen distribution in concave microwell arrays for the formation of highly functional pancreatic islet spheroids by engineering the bottom of the microwells. Our new platform significantly enhanced oxygen permeability that turned out to improve cell viability and spheroidal functionality compared to the conventional thick-bottomed 3-D culture system. Therefore, we believe that this could be a promising medical biotechnology platform to further develop high-throughput tissue screening system as well as in vivo-mimicking customised 3-D tissue culture systems.

Original languageEnglish
Pages (from-to)185-196
Number of pages12
JournalActa Biomaterialia
Publication statusPublished - 2018 Jan

Bibliographical note

Funding Information:
This work was supported by the KU-KIST School Project ( R1435293 ), the National Research Foundation of Korea ( R1610511 ), and the Korea University Future Research Grant ( K1614471 ). S.Chung & Y. Jun were supported by NRF-2017R1A2B3007701 grant funded by MEST and HI14C3347 grant of the Korea Health Technology R&D Project . This paper is dedicated to late Professor Sang-Hoon Lee for his lifelong contribution to biomedical engineering.

Publisher Copyright:
© 2017 Acta Materialia Inc.


  • 3D spheroid
  • Concave microwell
  • Oxygen availability
  • PDMS thickness
  • Pancreatic islets

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology


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