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.
Highlights
Tissue Engineering (TE) approaches include the culture of stem cell seeded on a scaffold for cell growth and differentiation in an environment that mimics the native tissue
The radial outlet system was designed to ensure that the fluid exiting from every outlet branch converges into a single outlet going through the exact same distance, and keeping the fluid pressure drop homogeneous among all four outlet branches (Figure 1b)
Using a one-way ANOVA with no corrections for multiple comparisons (Fisher’s test) it was possible to observe that PCL and C8 materials do not present any response compared to the negative control (p > 0.05)
Summary
Tissue Engineering (TE) approaches include the culture of stem cell seeded on a scaffold for cell growth and differentiation in an environment that mimics the native tissue. In order to increase cell rate and time of survival, the culture medium has to be periodically replaced to supply nutrient and growth factors to cells and removal of toxic cell by-products from the culture to avoid cell necrosis and limit extracellular matrix formation [1]. This can be done by using dynamic culture conditions such as a perfusion flow bioreactor that facilitates mass transport and waste removal to/from the cells. In vitro studies show that electrical stimulation promotes cell proliferation, matrix development, maturation and cell differentiation [3]
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