Development of a Novel Perfusion Rotating Wall Vessel Bioreactor with Ultrasound Stimulation for Mass-Production of Mineralized Tissue Constructs.

Content Provider	Europe PMC
Author	Cha, Jae Min Hwang, Yu-Shik Kang, Dong-Ku Lee, Jun Cooper, Elana S. Mantalaris, Athanasios
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 mass-production 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. Supplementary Information The online version contains supplementary material available at 10.1007/s13770-022-00447-3.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9294093&blobtype=pdf
ISSN	17382696
Volume Number	19
DOI	10.1007/s13770-022-00447-3
PubMed Central reference number	PMC9294093
Issue Number	4
PubMed reference number	35532736
Journal	Tissue Engineering and Regenerative Medicine [Tissue Eng Regen Med]
e-ISSN	22125469
Language	English
Publisher	Springer Nature Singapore
Publisher Date	2022-05-09
Publisher Place	Singapore
Access Restriction	Open
Rights License	© Korean Tissue Engineering and Regenerative Medicine Society 2022
Subject Keyword	Rotating wall vessel bioreactor Perfusion Stem cells Low-intensity ultrasound 3D mineralized tissue constructs
Content Type	Text
Resource Type	Article
Subject	Medicine Biomedical Engineering