Release date: 2018-07-03
Last month, a replica that mimicked the upper part of the human respiratory tract was officially launched – a human trachea made of collagen and two bronchi. Collagen is an essential binding agent for the human body. It gives the replica a smooth texture and a hollow structure that feels like a spaghetti that has not yet been cooked.
This trachea replica comes from a refrigerator-sized 3D printer supplied by United Therapeutics in Manchester, New Hampshire. The combined treatment company sells lung treatment drugs every year, with a turnover of more than one billion dollars.
Recently, the company claims to use a similar printer to produce "unlimited" human lungs to solve the serious shortage of donor organs today.
Bioprinting is nothing new. We know that 3-D printers have been able to make human skin, retina, and more. However, this technique is currently only suitable for the production of tissue cells that are very small, thin and have no blood vessels. In order to overcome this limitation, the United Therapeutics decided to focus on developing a printer capable of producing higher quality human lungs in the next few years – it can print solid, flexible and detailed human lung substitutes, including airways. 23 branches, alveoli capable of exchanging gases and an extremely fine capillary network.
In the company's view, the human lung substitute made of collagen mentioned at the beginning is nothing at all, because it is like a rubber-made toy chicken and a real hen can not be compared. Therefore, the combination therapy company plans to infiltrate the organ replicas in the human cell matrix, allowing human cells to attach and penetrate into the organs, allowing the organs to "live". Derek Morris, a project leader from product development, said they are trying to build a small adhesion chamber that allows cells to grow inside.
Organ manufacturing tycoon
This 3-D printing project is one of a series of highly invested projects initiated by CEO Martine Rothblatt. She used to be the founder of Sirius Satellite Broadcasting, but changed her job in the 1990s when her daughter was diagnosed with a rare lung disease.
When the joint treatment company was created, Rothblatt placed the bet on an undisputed $25,000 drug, making her the highest-paid CEO in the biopharmaceutical industry last year. At the same time, she also set a record for the fastest operation of electric helicopters. She also said that in the future, when a patient needs an organ produced by her company, the electric helicopter can deliver the product.
The United Therapeutics Company has always ventured to the forefront of this industry. Its subsidiary, Revivotor, has supplied heart, kidney and lung from GM pigs to the surgical field (currently used only on sputum). Another subsidiary, Lung Bioengineering, “renovated†the lungs donated by others by adding a temperature-friendly solution to the lungs that were supposed to be discarded. These lungs have been reintroduced by 250 patients with lung disease. use.
Still, Rothblatt admits that it takes at least 12 years to print a replacement that is exactly the same as a human lung. However, the United Therapeutics is the largest company in the industry of printing complete organs. Last year, a company called 3D Systems (3D Systems) in South Carolina was acquired; another company called 3Scan was also included in the capsule. They will carefully study the slices of human lungs and create a complete human lung inside. Structure diagram.
The joint manufacturing company's organ production department is located in the old textile mill of BioFabUSA, a company that is managed by the US Department of Defense and is worth $80 million to print tissue cells. As a senior executive and important investor in BioFabUSA, Dean Kamen said the meeting with Rothblatt prompted him to make a decision to apply to the government to manage BioFabUSA. The meeting allowed him to see the great potential of Rothblatt and see how scarce today's bioprinters are.
3-D printing technology overview
Today, this collagen-based 3D printing system works according to the principles of stereolithography. When ultraviolet light sweeps through a whole bunch of collagen of photosensitive molecules, the collagen solidifies. Gradually, the position of the first layer of material is lowered and placed on the bottom layer, and the new layer continues to be manufactured on this basis.
According to the company, the printer is capable of printing collagen with a resolution of 20 microns. But if you want to print a lung with a lot of detail, even the micron level of precision is not enough.
According to Pedro Mendoza, head of bioprinting at 3D Systems, the structure of the lungs is so complex that it can't match the fineness of 3D printing technology, whether it's machine-made or mold-casting. She added that the company's decision to dig out ideas from the semiconductor industry, such as photomasks, mirrors and more powerful radiation, can help improve the resolution of printer products. Current printing technology is also slow, and it may take a whole year to print the entire lung's stent structure.
Other applications of bioprinting technology
Some bioprinted tissues can be used almost in the medical field. Recently, a research team from Spain printed skin substitutes that they thought could be used for burn patients. However, the tissue printed today is only as thin as paper because there are no blood vessels. Organizations with larger areas may also die prematurely.
Although some researchers have already printed prototypes of living blood vessels, these are still at a very early stage. NASA in the United States has proposed to reward the first scientist who printed a one-centimeter thick living tissue ($300,000), but so far, the winners have not appeared, not to mention the difficulties and challenges of printing a lung weighing three pounds.
Sharon Presnell is from Organovo, Calif., which is responsible for printing thin, flexible liver slices. He said that many companies are busy printing out complete organs, but it may be too early to talk about them. “Where do we find the material that can print such a large vasculature? How much pressure can this material withstand?†Presnell explained his doubts.
How do I add cells to a printed model?
When it comes to how to make the model alive, the United Therapeutics believes that there are still many problems with current compression techniques. This extrusion method attempts to squeeze cells and proteins into a printed model through very thin needles. Luis Alvarez, head of organ production and bioengineering, commented that it was as difficult as pushing a water-filled balloon into a straw—the size of the cell significantly limited the resolution of the print.
Therefore, they decided to print the scaffold structure of the lungs first and then combine it with human cells. This process is also called recellularization. In fact, earlier, some teams discovered that the model made of collagen can actually be converted into a working lung. This year, Harvard University experimental surgeon Harald Ott (part of a joint treatment company) announced to the outside world that he injected billions of human cells from the umbilical cord and lung slices into the lungs of pigs that had lost their cells. When this refurbished lung was connected to the pig's circulatory system, they found that the basic function of the lungs had recovered. However, this experiment lasted only one hour.
According to Finn Hawkins, a stem cell biologist at Boston University, blood circulation and gas exchange have become possible in this trial. However, there is still a long way to go to successfully transplant organs. First, Ott's experiments lacked important cells, including wavy cilia that help to expel sputum. Second, we don't know where to find a large number of human cells to support the entire organ printing industry. At present, the lungs donated by people who have died can not meet this demand.
The United Therapeutics intends to use stem cells to mass produce the tissue needed for the trial, but they admit that this is not an easy task.
对 of new organs
If the organs can be produced in large quantities, this will not only solve the problem of organ shortage, but also prolong the life of human beings. Imagine what happens when you are 80 years old and you change your heart or lungs?
In order to achieve this goal, the joint treatment company may need to improve the technology step by step, rather than trying to take everything. But Alvarez believes that the company has decided to develop 3D stent printing, recellularization, and the use of stem cells to produce lung tissue, as these technologies may come together in the future. He said: "When we print out the finest part of the lungs, we know how to recellularize."
Source: DeepTech Deep Technology
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