JANUS: an open-source 3D printable perfusion bioreactor and numerical model-based design strategy for tissue engineering

João Meneses; Sofia R Fernandes; João C Silva; Frederico Castelo Ferreira; Nuno Alves; Paula Pascoal-Faria

doi:10.3389/fbioe.2023.1308096

JANUS: an open-source 3D printable perfusion bioreactor and numerical model-based design strategy for tissue engineering

Front Bioeng Biotechnol. 2023 Dec 15:11:1308096. doi: 10.3389/fbioe.2023.1308096. eCollection 2023.

Authors

João Meneses^{1

2}, Sofia R Fernandes², João C Silva^{3

4}, Frederico Castelo Ferreira^{3

4}, Nuno Alves^{1

5

6}, Paula Pascoal-Faria^{1

6

7}

Affiliations

¹ Centre for Rapid and Sustainable Product Development, Polytechnic of Leiria, Marinha Grande, Portugal.
² Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.
³ Department of Bioengineering and iBB-Institute of Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
⁴ Associate Laboratory i4HB-Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
⁵ Department of Mechanical Engineering, School of Technology and Management, Polytechnic of Leiria, Portugal.
⁶ Associate Laboratory for Advanced Production and Intelligent Systems (ARISE), Porto, Portugal.
⁷ Department of Mathematics, School of Technology and Management, Polytechnic of Leiria, Portugal.

Abstract

Bioreactors have been employed in tissue engineering to sustain longer and larger cell cultures, managing nutrient transfer and waste removal. Multiple designs have been developed, integrating sensor and stimulation technologies to improve cellular responses, such as proliferation and differentiation. The variability in bioreactor design, stimulation protocols, and cell culture conditions hampered comparison and replicability, possibly hiding biological evidence. This work proposes an open-source 3D printable design for a perfusion bioreactor and a numerical model-driven protocol development strategy for improved cell culture control. This bioreactor can simultaneously deliver capacitive-coupled electric field and fluid-induced shear stress stimulation, both stimulation systems were validated experimentally and in agreement with numerical predictions. A preliminary in vitro validation confirmed the suitability of the developed bioreactor to sustain viable cell cultures. The outputs from this strategy, physical and virtual, are openly available and can be used to improve comparison, replicability, and control in tissue engineering applications.

Keywords: bioreactor; capacitive-coupled; design; finite element analysis; modeling; multimodal stimulation; perfusion flow; tissue engineering.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Fundação para a Ciência e Tecnologia (FCT) - Portugal, and Centro2020 - Portugal, funded this work through projects Stimuli2BioScaffold (PTDC/EMESIS/32554/2017), OptiBioScaffold (PTDC/EME-SIS/4446/2020), InnovaBIOMAS (2022.10564. PTDC), CDRSP (UIDB/04044/2020 and UIDP/04044/2020), IBEB (UIDB/00645/2020), Associate Laboratory (ARISE LA/P/0112/2020), iBB (UIDB/04565/2020 and UIDP/04565/2020), InSilico4OCReg (PTDC/EME-SIS/0838/2021). JM received financial support from FCT under a PhD Studentship grant, reference 2021.05145.BD.