TISSUE ENGINEERING
Creating Tissues and Saving Lives
CONSTRUCTION OF TISSUES
After gathering up all of the materials, scientists now need to create the tissue. There are many methods that scientists can use to create tissue, such as bioreactors, long fiber generation, and organ printing.
BIOREACTORS
What is a Bioreactor?
To create tissues, scientists need to follow these steps:
-
First, build a scaffold.
-
After the scaffold is completed, add the cells. The cells can be with or without growth factors.
-
If everything is right, a tissue will develop.
A bioreactor does all of this but uses mechanics. They help the development of the tissue by providing signals for the cells to differentiate and grow.
(I.1)
Video explaining bioreactors and how they work
(V.1)
Requirements for Bioreactors
There are a few requirements for bioreactors, such as:
-
The bioreactor should be easy to build and take apart.
-
The material of the bioreactor should be able to interact with the tissue. This eliminates most metals, as they will cause a negative reaction.
-
The material should be usable at 37 degrees Celsius in a humid atmosphere.
-
The material should be able to be sterilized and be subjected to high temperature and pressure.
-
Finally, all the design elements should be completed. If the material needs to do a certain function, such as generate electrical currents, it should be able to.
(C.2)
There are different types of bioreactors, such as spinner flask, rotating wall, and flow perfusion. Each one has its purpose, advantages, and disadvantages.
(I.2)
Spinner Flask
One type of bioreactor is a spinner flask bioreactor. To create tissue, the scaffold is at the end of the needles in a medium, such as agar. The medium is stirred with a magnetic stirrer, going about 50-80 rpm. These type of bioreactors are best used for forming bone due to its high cell growth rate and calcium content.
Rotating Wall
Another type of bioreactor is a rotating wall bioreactor. This bioreactor has a cylindrical chamber that rotates. As it rotates, there is an upward hydrodynamic drag force that balances with the downward gravitational force, which keeps the scaffold suspended in the medium. As it continues to rotate, a tissue eventually forms. Rotating wall bioreactors are best used to form cartilage tissue due to effective nutrient transport and promoted cartilage growth.
(I.2)
(I.2)
Flow Perfusion
A third type is a flow perfusion chamber. It is made up of a pump and a scaffold chamber joined together by tubing. The scaffold is placed in the chamber and the pump forces media through the scaffold. This bioreactor can also be used for bone formation due to the enhanced nutrient transfer and increase in osteoblasts, which refines the bone.
Why are Bioreactors Important?
Bioreactors are important for research in the field of tissue engineering. In the human body, cells are exposed to signals that control their behavior. If they don't have these signals, cells become disorganized and eventually die. These signals can't be found by simply mixing cells and medium together. They need a bioreactor to mimic the signals so they can grow. Therefore, bioreactors are incredibly important when creating 3-D tissues.
(C.4)
LONG FIBER GENERATION
What is Long Fiber Generation?
Another method of creating tissue is long fiber generation. This technique was created by Dr. Hiroaki Onoe from the University of Japan.
With this technique, the tissues are created using cell-encapsulating hydrogel microfibers. For his experiment, Dr. Onoe used a collagen/alginate core-shell hydrogel microfiber. He used these steps to create the tissue:
-
First, cells (muscle, nerve, and endothelial) inside the core collagen multiply rapidly, filling it with "cell fiber" over the course of 3-14 days.
-
Next, he removed the alginate shell outside of the cell fiber.
-
He placed the cell fibers into an aqueous solution by fluid flows generated with thin capillaries without damages. Finally, the cell fibers were weaved and reeled and then placed on a tissue graft.
The potential for long fiber generation is endless. For one, it would allow scientists to construct internal, intricate networks of tissue, as well as transplant fiber tissue grafts with minimal invasion.
(C.5)
Diagram explaining the steps that Dr. Onoe took when performing his experiment with long fiber generation
(I.3)
ORGAN PRINTING
What is Organ Printing?
Organ printing is the process of creating living organs using materials such as cells, biological molecules, and biomaterials. This method can be used to create organs that could be used in medical testing.
(C.6)
Dr. Anthony Atala talks about printing organs such as kidneys during a TED Talk
(V.2)
How Does Organ Printing Work?
These are the steps to printing an organ using a bioprinter:
-
First, scientists need to create a blueprint. They use software to create a digital image of the organ that they wish to print.
-
Next, you need the ink. Unlike traditional printers, bioprinters use "bio-ink". Bio-ink is made up of the cells of the patient who needs the organ. The cells are taken and cultivated, then turned into bio-ink.
-
Then, the bio-ink is placed inside of the printer, and the blueprint is sent. The printer reads the blueprint and inserts cells where they are needed. It is closely done layer by layer. However, cells alone won't hold together. So, bioprinters often use a type of gel that acts as a glue to hold the cells together.
-
Layers and layers are placed over the course of several hours, finally creating an organ.
(C.6)
Many tissues and organs have been created using bioprinters. Some of them include bone, skin, and cartilage. Below is more information about the experiments conducted, creating these tissues and organs.
Bone
At the University of Nottingham in England, they are working on creating printed bones. First, they print a copy of the part they want (this part becomes the scaffold). Next, they combine adult stem cells and bio-ink, creating printed bones. The bones were then implanted and after three months, the scaffold will be replaced by actual bone produced by the body.
(C.6)
(I.5)
(I.4)
Skin
At the Wake Forest School of Medicine, scientists have built a bioprinter that can print skin cells directly on a burn. First, a scanner figures out the size of the wound. The cells that are needed are created by the scientists. Then, a combination of cells and ink is used to heal the wound. The ink is made up of enzymes and collagen. What makes this bioprinter special is that scientists only need a small patch of skin to grow skin cells to heal the burn.
Cartilage
In Zurich, Switzerland, scientists have developed a method for creating nose cartilage. This is how the technology worked:
-
First, scientists extract cartilage cells from the patient.
-
The cells are grown in a lab and mixed with a biopolymer.
-
With this mixture, the bioprinter creates nose cartilage.
This experiment was successful. After a few months of implantation, scientists couldn't find the difference between the natural and artificial cartilage.
(C.6)
(Left) A blueprint of the nose, courtesy of modeling software
(Right) The finished product inside of a petri dish, a nose
(I.6)
Why is Organ Printing Important?
As organ printing advances as a field, the possibilities are endless. Here are some of the things that organ printing can be used for:
-
Using artificial tissues for testing. It can be used for to test the toxicity of drugs. This can reduce the number of animals used for testing.
-
Find new solutions for problems. Organ printing can help solve many problems that were once thought impossible. Eyes can be made for blind people, people with bad hearts can get new ones, and life can improve for people suffering from horrible diseases.
-
Solve the problem of organ donation. Every year, more and more people need organs. However, there are fewer donors as well. Organ printing can solve this problem by providing organs for people who desperately need them. No longer would people have to wait years, and possibly die, before getting a new organ.
(C.6)