A Multimodal Stimulation Cell Culture Bioreactor for Tissue Engineering: A Numerical Modelling Approach

Abstract

The use of digital twins in tissue engineering (TE) applications is of paramount importance to reduce the number of in vitro and in vivo tests. To pursue this aim, a novel multimodal bioreactor is developed, combining 3D design with numerical stimulation. This approach will facilitate the reproducibility between studies and the platforms optimisation (physical and digital) to enhance TE. The new bioreactor was specifically designed to be additive manufactured, which could not be reproduced with conventional techniques. Specifically, the design suggested allows the application of dual stimulation (electrical and mechanical) of a scaffold cell culture. For the selection of the most appropriate material for bioreactor manufacturing several materials were assessed for their cytotoxicity. Numerical modelling methods were then applied to the new bioreactor using one of the most appropriate material (Polyethylene Terephthalate Glycol-modified (PETG)) to find the optimal stimulation input parameters for bone TE based on two reported in vitro studies.

Medicated multi-targeted alginate-based dressings for potential treatment of mixed bacterial-fungal infections in diabetic foot ulcers

“…The cell viability decreased with increasing amount of FLU in the combined DL dressings implying that the biocompatibility is dependent on the dose of FLU. However, none of the formulated combined DL dressings were considered cytotoxic according to ISO standard since all the combined DL dressings showed > 70% cell viability (Meneses et al, 2020). the proliferation of human PEK cells after 24 h seeded at a density of 1 x 10 5 cells/ml with the combined DL dressings.…”

Chitosan‐gelatin/hydroxyapatite‐based scaffold associated with mesenchymal stem cells differentiate into osteoblasts improves the surface of the bone lesion in mice C57BL/6J

“…[10][11][12][13] The strategy in BTE involves harvesting cells from humans or animals, expanding them in vitro, and eventually differentiating them. 14 The cells are seeded in an optimized scaffold, designed and developed to reproduce the bone characteristics in vivo. The scaffold with the cells is subsequently implanted at the lesion site (Figure 1).…”

“…Cells can be obtained from autologous, syngeneic, allogeneic, or xenogeneic sources, and diverse scaffolds can be prepared from different materials to realize their desired properties 10–13 . The strategy in BTE involves harvesting cells from humans or animals, expanding them in vitro, and eventually differentiating them 14 . The cells are seeded in an optimized scaffold, designed and developed to reproduce the bone characteristics in vivo.…”

Design, fabrication, and characterization of a multimodal reconfigurable bioreactor for bone tissue engineering

“…Another important issue related to bioreactors in BTE is the lack of uniformity between each developed stimulation device. Differences in the bioreactor culture chamber geometry, scaffold material and size, type of exploited physical stimuli, and type of cell line used in experiments complicate the understanding of osteodifferentiation processes (Castro, Ribeiro, et al, 2020; Meneses et al, 2020; Rangarajan et al, 2014; Van Dyke et al, 2012). BTE lacks of a comprehensive knowledge, and culminates in the growth of partial information that does not consider fundamental parameters of bone tissue regeneration—like the presence of different correlated biophysical inputs—thus hampering the possibility to draw conclusive statements from the related observations.…”