Predicting and controlling bubble clogging in bioreactor for bone tissue engineering

A common problem in small scale bioreactors like those used for tissue engineering is the clogging of microchannels by gas bubbles. In case of clogging, the flow distribution inside the bioreactor changes and can not guarantee the adequate transport of nutrients and efficient removal of catabolites. Bubbles may (i) enter with the flow during the priming phase, when the reactor is first filled with the culturing medium, or may (ii) form locally during operations, because of gas desorption from scaffold, intense cellular metabolic activity or degassing. In this work, we develop and use an analytical model to identify the conditions (bioreactor region, flow rate, limiting bubble size) for which bubbles may adhere stably to the scaffold, potentially leading to bubble clogging. Based on the flow and shear stress distribution calculated by numerical simulation, the model indicates that clogging may occur in the region around the scaffold and along scaffold channels. Operative conditions under which clogging can be avoided are identified.