constructions with greater resistance than those developed without

any mechanical stimulation [10–13]. So, these stimuli can act as

antagonists for more expensive approaches, which often use growth

factors, in a more specific and targeted way.

A more direct method of mechanical stimulation makes use of

models of compression bioreactors, which can vary from uniaxial to

multiaxial and allow for the insertion of different variables which

act directly on the scaffolds. Since there are no standardized loading

protocols, the results obtained by the several studies previously

published, impose a difficult task to compare these protocols.

However, the dynamic loading parameters including amplitude,

frequency and load duration clearly influence biomechanical and

biochemical results in these studies [14–19]. The intermittent

compressive load, for example, is rather efficient than a continuous

one, since the resting period allows the cells to respond to the

mechanical stimuli during this gap [15, 16, 20]. Thus, considering

all these aspects, the method here described focuses on the applica-

tion of two real-time modes of mechanical stimulation: compressive

loading and fluid dynamic. Both modes, when applied simulta-

neously and in the chosen parameters, are able to provide an

environment that improves cell activity in 3D scaffolds when com-

pared to standard static culture approaches (Fig. 2).

Fig. 1 Laser scanning confocal microscopy images of aggrecan labeling under static conditions or in

bioreactor under fluid flow. Indirect labeling for aggrecan is identified in red by Alexa Fluor 647. Bars

50 μm. (Adapted with permission from Springer: Biotechnology Letters, Ref. 6, Enhancement of cartilage

extracellular matrix synthesis in Poly(PCL-TMC)urethane scaffolds: a study of oriented dynamic flow in

bioreactor, Pedrini et al., 2020)

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