Slide 1:

Hello, and welcome to Module 6 of the tissue engineering series. Today we will be talking about bioreactors.

Slide 2:

So what is a bioreactor? A bioreactor is a device that recreates a biological microenvironment in order to facilitate the growth of cells and tissues. When growing these cell cultures, a bioreactor often controls a set of common parameters. It will monitor the pH levels of the growth medium, the temperature, the oxygen levels, and the amount of nutrients the cells will be receiving.

Not only can cells die if levels are incorrect, but when the environment is controlled in such a manner, we can ensure that there is consistency across all of our trials.

Consistency is essential in research. You have to fully understand what is changing in your trials. If you have multiple independent variables, you cannot draw an accurate conclusion about the data.

Slide 3:

Oftentimes, bioreactors are modeled after the human body.

The human body has been practically perfected over millions of years of evolution and has mastered the art of cultivating new cell and tissue growth.

Our respiratory system captures oxygen and our cardiovascular system sends this out to our cells. The digestive system breaks down food into precious nutrients and the nutrients are then carried to cells by the cardiovascular system. We want to take into account how all of these systems promote and affect cell and tissue growth and replicate this within our bioreactor.

This is the main goal of creating a bioreactor: to simulate the systems of the human body and provide cell and tissues optimal conditions for growth. The bioreactor must also provide a sterile environment ensuring that no outside contamination can affect the cell and tissue growth in any way.

The medium the cells grow in must be monitored for its pH levels, temperature, and oxygen content in real-time. The system must also be automated. The bioreactor needs to have the ability to self-correct if any of these measurements are off.

Lastly, the bioreactor needs to be inexpensive. The bioreactor relieves the necessity for a laboratory technician to feed cells every day. Decreasing manual labor will save on both time and money.

Slide 4:

Here is a picture of an actual bioreactor used by STEL Technologies, LLC. This little box here is where the tissues will grow.

Normally tissues are grown in cell culture dishes, however, everytime one opens the lid you risk contamination. By growing the tissues in this bioreactor, the only risk of contamination is when the cells are initially placed inside. After that, the cells are able to grow into tissues without any outside assistance. This is called a closed-system bioreactor.

An example of what makes this bioreactor unique can be seen in the picture on the goth. It is able to grow co-cultures, meaning it can grow 2 different tissues at the same time, and fuse into one multiphasic, multitissue construct with functional interfaces. Where multiphasic refers to the variation of structure and chemical composition.

In this image from STEL technologies bone and ligament tissue have been grown and combined together into a single construct. Each image below shows the cells under a microscope where alizarin red and H and E are stains allowing for collagen and nuclei of the cells to be visible.

With current technology, the size of these constructs are only limited by the size of container they grow in. Bone- ligament - bone constructs have been grown by STEL technologies up to 20 cm long.

Slide 5:

Here we will go over the general workings of the bioreactor. After the cells are placed inside, the bioreactor follows a general flow of order.

A medium reservoir is prepared, which will be used to provide nutrients to the cells. The temperature is controlled by the orange heating jacket surrounding the reservoir. One of the tubes on the top will oxygenate the mixture. Once the medium inside reaches the desired levels, tt is pumped through an inlet tube to the conditioning sensors. The conditioning sensors will measure the medium to ensure the levels are correct. From there a computer controlled value will control flow of the medium into one of the three chambers or back into the reservoir.

These chambers are each individual bioreactors that will be where the engineered tissues will actually grow. Each bioreactor is able to grow 1 co-cultured tissue as described previously. Once the medium runs through the bioreactor, it is then pumped through an outlet and run past sensors to determine what is in the waste media. the waste media is dumped then into the waste reservoir.

This concludes module 6, you are now able to move on to module 7,