Important Functional Goals:

The four most important goals are accommodation, mechanical loading, chemical modulation, and visualization of the physis. Each of these categories and their importance are explained below:

Accommodation of Physis (50%): In order to study the physis and changes to growth based on different types of stimuli, the physis itself must be kept in an environment in which it can survive and grow close to what would be seen in vivo. This includes maintaining a suitable pH, CO₂ level, humidity, temperature and a constant source of nutrients as well as ensuring that any parts of the bioreactor that the physis is exposed to are kept sterile. The dimensions of the physis slices before growth must also be uniform (with a constant thickness which allows for lateral/longitudinal growth) and the bioreactor must be able to allow for at least 3 control/experimental samples. This goal was weighted as such because accommodation of the physis is highly integrative and essential to being able to run experiments.

Mechanical Loading of the Physis (20%): In order for the bioreactor to be used in a way that yields clinical relevance, it needs to be able to accurately place a load of known amount on a slice of growth plate tissue. Compressively, the bioreactor must be able to compress the physis longitudinally from the epiphyseal side to the metaphyseal side. The physis must also be secured during loading so that it doesn’t slip. This goal was weighted as such because the bioreactor needs to be able to load the physis to test and quantify mechanical properties.

Chemical Modulation (20%): Because the physis physiologically has a gradient-like nutrient flow which is mediated via epiphyseal and metaphyseal arterial invasions, the bioreactor needs to facilitate a similar type of flow which allows for nutrients, growth factors and other materials that the physis consumes to flow into the physis from the epiphyseal and metaphyseal ends. In addition, mass transfer of delivered materials needs to be accounted for. This goal was weighted as such because the physis needs to grow in a fashion similar to what is seen in vivo in order for there to be clinical relevance.

Visualization of the Physis (10%): The bioreactor should allow for periodic imaging of the physis so that the user can image the physis as a whole and any regions of interest. This goal was weighted as such because imaging can be done in a number of ways and is usually independent of any stimuli that the physis experiences.

Constraints

A major constraint faced was that of time. Experiments needed to be fairly short in order to test multiple design factors but long enough to see visible growth, which means that the bioreactor needed to be able to sustain/load growth plate tissue for a few days to a week at a time. In addition, the time that the growth plate spends outside of the bioreactor without media (for imaging or other purposes) needed to be minimized to ensure that it was kept alive.

Material expenses were another constraint. The cost of chondrocyte media, growth factors and machined parts required to create and test the bioreactor made it important to optimize resource utilization.

In terms of physical and biological constraints, the growth plate needed to be constrained thickness-wise so that lateral and longitudinal growth can be observed and measured. The physical boundaries of the growth plate were be based on where bone is attached and where the physis is sectioned. Materials around the physis needed to be observed for boundary-like conditions. The physis had to be restrained during loading in a manner that doesn’t damage it.