Tissue Eng Regen Med.
2022 Aug;19(4):739-754. 10.1007/s13770-022-00447-3.
Development of a Novel Perfusion Rotating Wall Vessel Bioreactor with Ultrasound Stimulation for Mass-Production of Mineralized Tissue Constructs
- Affiliations
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- 1Department of Mechatronics Engineering, College of Engineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Republic of Korea
- 23D Stem Cell Bioengineering Laboratory, Research Institute for Engineering and Technology, Incheon National University, Incheon 22012, Republic of Korea
- 3Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea
- 4Department of Chemistry, Research Institute of Basic Sciences, Incheon National University, Incheon 22012, Republic of Korea
- 5Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan 570-749, Republic of Korea
- 6Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
- KMID: 2533912
- DOI: http://doi.org/10.1007/s13770-022-00447-3
Abstract
- BACKGROUND
As stem cells are considered a promising cell source for tissue engineering, many culture strategies have been extensively studied to generate in vitro stem cell-based tissue constructs. However, most approaches using conventional tissue culture plates are limited by the lack of biological relevance in stem cell microenvironments required for neotissue formation. In this study, a novel perfusion rotating wall vessel (RWV) bioreactor was developed for massproduction of stem cell-based 3D tissue constructs.
METHODS
An automated RWV bioreactor was fabricated, which is capable of controlling continuous medium perfusion, highly efficient gas exchange with surrounding air, as well as low-intensity pulsed ultrasound (LIPUS) stimulation. Embryonic stem cells encapsulated in alginate/gelatin hydrogel were cultured in the osteogenic medium by using our bioreactor system. Cellular viability, growth kinetics, and osteogenesis/mineralization were thoroughly evaluated, and culture media were profiled at real time. The in vivo efficacy was examined by a rabbit cranial defect model.
RESULTS
Our bioreactor successfully maintained the optimal culture environments for stem cell proliferation, osteogenic differentiation, and mineralized tissue formation during the culture period. The mineralized tissue constructs produced by our bioreactor demonstrated higher void filling efficacy in the large bone defects compared to the group implanted with hydrogel beads only. In addition, the LIPUS modules mounted on our bioreactor successfully reached higher mineralization of the tissue constructs compared to the groups without LIPUS stimulation.
CONCLUSION
This study suggests an effective biomanufacturing strategy for mass-production of implantable mineralized tissue constructs from stem cells that could be applicable to future clinical practice.
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