Image source @ Visual China
Text | Cybermed Cyber Doctor
In the movie "The Island", the hero and heroine go to Xanadu Island to enjoy the beautiful life, and what they never expect is that they go to the island to take out their living organs to save others. They were born and raised only to save humanity, a group of humans who need fresh organ transplants...
In fact, the proposition that "human beings need fresh organs" is not a fiction, but a bloody reality. In 2016, the United States waited for about 160,000 organ transplants, and only 16,000 organ donors; China waited for about 300,000 organ transplants every year, while only 10,000 donated organs.
In 2019, a total of 40,608 post-death organ donations were completed globally, but only about 10% of the global demand for organ transplants was met.
The medical profession has called the lack of donors "a crisis." With the development of science and technology and the importance of human health, the manufacture of active organs in vitro has become a research hotspot - 3D bioprinting technology has become the first choice.
<h2>01 Clinical significance of 3D bioprinting</h2>
Linking 3D printing to living matter is Professor Thomas Boland of Clemson University. In 2000, Professor Boland first proposed the concept of "cell and organ printing technology". In 2003, the team successfully printed living cells for the first time and published the world's first paper on biological cell printing, achieving a leap from printing inanimate substances to living substances.
In fact, before this, 3D bioprinting in a broad sense already existed, but the clinical significance was different.
As early as 1992, SLA (Optical Immobilization Stereoscopic Modeling in RP Technology)
Technology has been used for preoperative simulation of craniomaxillofacial surgery, and the door to surgical guidance by 3D printing has been opened. It provides support for 3D printing to realize the development of traditional medical models to anthropomorphic medical models. This is the first layer of clinical significance of 3D bioprinting: the manufacture of structures without biocompatibility requirements, and the products are used for surgical path planning.
In 2007, Italian orthopedic medical device company Limage Corporate launched the world's first 3D printed standardized hard tissue repair product, the implantable acetabular cup Trabecular Titaniumtm, which was CE certified. This is the second meaning of 3D bioprinting for the clinic: the manufacture of biocompatible implants with biocompatibility requirements. For example, titanium alloy joints, defect repair of silicone, prostheses and so on.
Using the 3D printing method to print biocompatible and degradable products is the third meaning of 3D bioprinting in the clinic. For example, teeth. Using 3D printing technology to print out a titanium multi-root dental implant with a connected porous structure, the void is 300~400 μm, through animal experiments and controls, the 3D printed dental implant has good bone binding ability, and the bone tissue grows into the surface gap of the implant, with high bone tissue density.
After solving the first three layers of needs, the diligent human beings began to climb another peak in the 3D bioprinting industry: cell-loaded printing. That is what we call 3D bioprinting in the narrow sense today: manipulating living cells, constructing bionic three-dimensional tissues, printing cell models, units, skins, and blood vessels. Or, print a functional organ.
<h2>02 From shape to god</h2>
Essentially, bioprinting is just an advanced form of the ordinary printing process. Imagine millions of people working through printers to make hardware copies of files or photos. In fact, 3D bioprinting is similar to the ordinary printing process: it needs to be designed before printing, and it needs printers and ink when printing, and it ensures quality after printing.
At present, mainstream 3D bioprinting technology can be divided into five categories: extrusion bioprinting, finite element bioprinting, inkjet bioprinting, laser-assisted bioprinting and micro-valve bioprinting.
The process is the same, but the requirements are obviously different. Previous commentators have argued that there are four major challenges in the 3D printing world: cell technology, biomaterials, manufacturing platforms, and vascular supply systems.
Different tissues of the human body are composed of different cells, such as epithelial cells in the skin and cardiomyocytes in the heart. Which of these cells are suitable for in vitro isolation and culture? Which ones can maintain their biological activity after cultivation? Cultivating value-added technologies is a prerequisite for the success of 3D bioprinting.
Moreover, different tissues and organs have different characteristics. For example, soft skin, hard bones. 3D printing requires biological materials that correspond to tissue properties, and the selected materials must be able to operate through 3D printing systems.
In addition, whether it is extrusion, inkjet, or micro bio-valve printing, each printing method has its own advantages and disadvantages and hardware technology requirements. How to ensure that the 3D printing system exerts maximum efficacy while maintaining the biological activity of cells and the physical properties of biological materials, and meeting the standards of medical applications, is not an easy task.
But it is not insurmountable.
Professor Boland and his team applied for the world's first patent for cell and organ printing in 2004. And licensed to 3D bioprinting company Organovo. The latter is currently the popular spicy chicken in the global 3D bioprinting market.
In 2010, Organovo printed the world's first blood vessel, taking the lead in realizing the commercialization process of 3D printed blood vessels;
In 2011, China's 3D printed standardized soft tissue repair products of China's Maipu Medicine, the absorbable hard brain (spinal) membrane, obtained CE certification; in 2012, Scottish scientists printed liver tissue for the first time using human cells as materials.
<h2>03 The Ultimate Question</h2>
It is said that a painting hangs on the wall of Harvard Medical School that describes and documents the world's first organ transplant in 1954. So organ transplantation has been around for 67 years in human history. Now what 3D bioprinting has to solve is to implant laboratory tissue into the human body.
The pioneer was the famous Professor Anthony Atala. The time is 2001.
In 2001, at the age of 10, Luke Massella had to face reality: "I may have to face the problem of having to survive dialysis for the rest of my life, I can't play sports, and I can't live a normal child life like my brother." 」 He survived more than a dozen surgeries because of congenital spina bifida. However, his bladder began to have problems again, and his kidneys began to fail.
Luckily, he met Anthony Atala, a surgeon at Boston Children's Hospital at the time. Dr. Anthony and his team took a small piece of Luke's bladder and spent more than two months engineering a new bladder in the lab. Then, during a 14-hour surgical procedure, the doctor replaced the defective bladder with a new one.
Now twenty years later, Luke Massella has worked in a variety of careers, including school wrestling coaching. He has not had any other surgeries since he was 13.
Dr. Anthony is the current research leader at WFIRM (Wake Forest Institute for Regenerative Medicine at Wake Forest University). The agency has made a name for itself in the history of 3D bioprinting.
For more than two decades, the team has invented artificial bladders, artificial vaginas and urethras; in 2020, they announced that the use of bioengineered repairs of "artificial wombs" allowed rabbits to give birth to surviving offspring. This time, the team hopes the technique will eventually replace uterine transplants, giving women with uterine dysfunction the opportunity to have offspring.
In 2013, the University of Michigan Public Health Center used the technology to create an artificial trachea and successfully carried out the world's first 3D printed organ human transplant; in 2017, Organovo demonstrated its own liver tissue 3D printing technology, and has been successfully transplanted into the body of laboratory mice. The company claims that the next step is clear, and that is humanity itself.
In April 2019, the world's first 3D printed artificial heart was born, from a research team at Tel Aviv University in Israel. Using human adipose tissue, a "artificial heart" with cells, blood vessels, ventricles and atrium was successfully 3D printed. Although only the size of a rabbit's heart, it demonstrated the feasibility of studying such artificial hearts for organ transplantation. A year and a half later, in November 2020, Carnegie Mellon University printed a full-scale model of the human heart.
It seems that humans are already within reach of printing an organ that can be transplanted. But in fact, in addition to the above-mentioned cell technology, biological materials, and manufacturing platforms, the most difficult is the vascular supply system: the human body's tissues and organs are living in the vascular system, and sufficient blood supply is a necessary condition for maintaining biological activity. But current 3D bioprinting technology is not yet fully capable of creating a comparable alternative to human beings, let alone fusing the vascular system into 3D printed tissue. Whether 3D printing can print organs with a vascular system and integrate into the entire blood circulation system of the human body is a big problem in this industry.
In addition, for cell printing, the controllability of bioink, the activation of the printing structure, and the functionalization of the printing structure can be summarized as the three basic scientific problems covered by its control control, and to solve these problems, it is necessary to overcome a series of problems from the synthesis of ink, the regulation of the printing process, the construction of nutrient delivery channels to the induction of functionalization.
But even if all of the above problems can be effectively solved, there is an ultimate problem: once human organs can be produced on a large scale like products on the production line, what is the ultimate purpose of human existence as a human being? If one person's organ may be enhanced by an industrial product, how can the problems for others be solved? If a person as a whole could be copied, such as a clone of the movie mentioned at the beginning of this article, would a replicant appear?
Kant said, "Never simply use man as a tool, but always as an end, whether for yourself or for others." ”
You tell me?