If you want to know how close we are to a fully functional organ being made in the lab… stay tuned. Today’s materials science basics topic is Tissue Engineering. This is a topic near and dear to my heart because I spent my graduate school years studying tissue engineering. This post will answer what tissue engineering is, how tissue engineering works, how close we are to engineering a full organ in the lab, and what challenges are ahead for whole organ tissue engineering.
Importance of Tissue Engineering
Tissue engineering combines cells, materials, and engineering techniques to repair or replace biological tissue. That can mean helping speed up repairing a broken bone or the ultimate goal of replacing entire organs. Every 10 minutes, a new person is added to the organ transplant list, and unfortunately, about 8000 people die each year waiting for an organ transplant. This means there is a critical need for more organs that can be used for transplants. Whole organ tissue engineering is one way that challenge is being tackled.
How Tissue Engineering Works?
So before we talk about how close we are to a full-function organ, let’s answer how tissue engineering works. Tissue engineering is a science field that uses cells, materials, and engineering to repair or replace tissues and organs.
Cells
Depending on the tissue or organ that scientists are trying to repair or replace, they use cells critical to the function as a starting point. An example of this would be skin tissue engineering; scientists take fibroblasts or keratinocytes. These cell types are critical to the skin’s production, to create skin grafts. The resulting skin grafts can be placed on areas that do not have skin. The cells on the grafts work with the cells in a person’s body to create a new skin layer.
Materials
In addition to needing cells critical to the function of the tissue or organ that is being replaced, it is also important to have a template for the cells to grow. These templates are called scaffolds. Scaffolds are important because they give the cells a lot of cues as they grow new tissue. Some of these cues include
- Telling the cells what shape they should grow in
- Giving the cells cues on how quickly they should grow
- What molecules they should produce to help make growing easier
- Cue cells to recruit assistance once they are implanted in the body.
Many different materials are used to modulate the cell’s behavior. If you are curious about the types of materials used for tissue engineering, let me know the comments below. One of the most popular scaffold materials is collagen. Although it is not super effective when applied on top of your skin, it can be a great starting point for growing new tissues and organs.
Engineering Techniques/ External Stimulus
The last but definitely not least important component of tissue engineering is engineering techniques. A better word for engineering techniques is an external stimulus. The human body is an amazing and very dynamic environment. This means that the tissues and organs of the human body have to respond to the dynamic environment and the cells that make them up rely on the dynamic environment to grow and thrive.
For example, a group of cells in the heart called cardiomyocytes help keep a heart beating. When scientists tried to grow them outside of the body, they could not produce functional cells. Ultimately, they realized to get functional cardiomyocytes; they had to expose them to the expanding and contracting that modeled a heartbeat while growing them. Tissue engineers refer to this expanding and contracting as a mechanical stimulus.
Depending on the tissue they are trying to grow, the type of mechanical stimulus they need can vary. For cells that grow on blood vessels’ walls, shear stress that models blood rushing past them is critical. Many studies show that the best cartilage replacements are produced when the cells are stretched and compressed while growing. The stimuli the cells are exposed to do not only have to be mechanical. There are chemical stimuli that the cells can be exposed to, like growth factors, other cells, and chemicals that can also encourage beneficial functions.
History of Tissue Engineering
Now that we have talked about how tissue engineering works, let’s talk about the history and how close we are to tissue engineering, a fully functional organ.
The Birth of the Field of Tissue Engineering
First, we have to rewind to the 1970s when W.T Green tried to grow cartilage in mice. Although he was not successful, he concluded that the invention of biocompatible materials combined with cells would make it possible to grow new tissues. Spoiler alert, he was right. Later he produced sheets of cells and place them on burn patients to help them regrow skin. However, it was not until about 10 years later, in the 1980s two scientists Joseph Vacanti and Robert Langer, successfully used material with cells on it to regrow a tissue
Tissue Engineering Becomes a Topic in Popular Culture
Although this was noted as the birth of tissue engineering, it was not until the 1990s that tissue engineering was thrust into popular culture by Dr. Vacanti successfully growing an ear on a mouse’s back. Although it was not a functional ear, and it was actually ear-shaped cartilage. Regardless, this was a huge advance for the world of tissue engineering because it was the first full organ grown in a lab.
Development of the Bioprinter
In the early 2000s, a scientist named Thomas Boland modified an inkjet printer, which had only been invented twenty years earlier, to print cells into a petri dish. This was the first bioprinter, and today, bioprinting is one of the primary techniques for whole organ tissue engineering.
The First Functional Organ Partially Grown In a Lab
In the mid-2000s, a scientist named Atala took cells from patients and grew them on a collage scaffold shaped like half of a bladder. They were grown outside of the body for 7 weeks and then reimplanted into the human patients. The composite bladders that were not in the patients were fully functional and looked microscopically similar to the normal human bladder. This was a huge step in organ tissue engineering, but this still was not an entire lab created organ.
Development of Decellularization
In the late 2000s, decellularization was developed that involved taking organs that had previously been in a human or animal and removing all of the biological contents except for the structural proteins. This process is called decellularization because you remove all of the cells and cellular components. It is actually really cool because the organs become a translucent color once it is complete.
Successful Use of Decellularization in the Lab
After decellularization, the first successful demonstration of engineering an entire organ took place in a rat. The scientists decellularized a rat heart and then used a perfusion reactor for 28 days. This provided the mechanical stimulus we talked about earlier. Then, it successfully reimplanted it into a rat. This was a huge success; however, they could only achieve pumping function, so a movement of blood that was equivalent to 2% of an adult heart and 26% of a newborn’s heart. So getting closer but still not quite there.
A year later, a group of researchers used those learnings and repeated the process in a rat’s liver. It was a fully functional organ, and this was the closest we have gotten to the development of a fully functional organ made through tissue engineering. As scientists have more time to work on it and understand the complexities of organs, I am sure that they will successfully tissue engineer a whole organ.
Challenges for Whole Organ Tissue Engineering
Vascularization
Some of the challenges that are holding them back include creating a vascular network so that the cells on the innermost portion organ get their critical oxygen and nutrients. In our bodies, the blood vessels are the delivery vehicles for oxygen and other nutrients our cells need to survive. These same pathways have to be present in these tissue-engineered organs to grow and produce a functional organ for the cells in them.
Long-Term Viability and Functionality
The next challenge is long-term viability and functionality. Like the work done with the rat heart, scientists have been able to achieve organs with partial function or full function but only for a short time. To have organs transplanted into a perform, they would need long-term sustained full function.
Mass Production of Tissue Engineered Organs
Next is the problem of mass production. About 200,000 people on the organ transplant list between the life-saving and active waiting lists, and to produce a single organ, it can more than 4 weeks in highly specialized equipment run by highly trained scientists. This creates limitations in the number of organs that can be produced
There are also debates about the types of cells that are ethical to use for these applications, but I do not want to get into that. Despite the number of limitations, this field still has so much promise.