Cell culture bioreactors play a paramount role in obtaining successful cell cultures that mature into tissue-like structures. Cellular growth is accomplished by supplying the seeded cells with sufficient nutrients while performing an adequate removal of cellular metabolic waste products [1]. At the same time, it is necessary for the cellular environment to maintain adequate biological levels of pH, temperature, gas concentration (O2, CO2), and hydrostatic pressure.
The current work presents a new methodology to create a shareable and easily reproducible cell culture bioreactor based on open source technologies, accessible materials, and ubiquitous construction techniques. Our bioreactor designs are continuously supported by corresponding digital twin numerical models to optimize their operation in current tissue engineering processes [2]. Numerical models also play a key role in understanding the local conditions imposed and consequent cellular effects, especially when cellular environmental conditions become unfavorable or are very difficult to measure and control. Specifically, our research is focused on modeling the delivery of external stimulation modalities, such as electromagnetic, fluid flow, wall shear stress, and hydrostatic pressure. Our overall goal is for our predictions to ultimately help to obtain critical insights into the environmental cues that lead cells to differentiate, proliferate, grow, and, finally, mature into tissues of interest.
As part of this project, we will present the developed bioreactor designs that will allow the validation of the digital twin models proposed. We will also present a detailed analysis of new developments and opportunities for numerical models and bioreactor in tissue engineering applications.
Author Contributions
Conceptualization, P.P.-F. and N.A.; methodology, P.P.-F. and N.A.; software, A.D. and J.M.; validation, J.S., P.P.-F. and N.A.; writing—original draft preparation, P.P.-F. and J.M.; writing—review and editing, C.M., F.F. and N.A.; supervision, P.P.-F. and N.A.; funding acquisition, P.P.-F. and N.A. All authors have read and agreed to the published version of the manuscript.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: CDRSP is funded by Fundação para a Ciência e Tecnologia (FCT), Portuguese national funding agency for science, research and technology, and by Centro2020 through the following projects: OptiBioScaffold, Ref. PTDC/EME-SIS/4446/2020; UIDB/04044/2020; UIDP/04044/2020 and PAMI-ROTEIRO/0328/2013 (Nº 022158). J.M. received financial support from FCT under a Studentship grant, reference 2021.05145.BD.
Informed Consent Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
References
- Kazimierczak, P.; Przekora, A. Bioengineered Living Bone Grafts—A Concise Review on Bioreactors and Production Techniques In Vitro. Int. J. Mol. Sci. 2022, 23, 1765. [Google Scholar] [CrossRef] [PubMed]
- Meneses, J.; Silva, J.C.; Fernandes, S.R.; Datta, A.; Castelo Ferreira, F.; Moura, C.; Amado, S.; Alves, N.; Pascoal-Faria, P. A Multimodal Stimulation Cell Culture Bioreactor for Tissue Engineering: A Numerical Modelling Approach. Polymers 2020, 12, 940. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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