Vietnamese scientist masters 3D printing technology for artificial blood vessels

After more than 2 years of pursuing advanced biological 3D printing technology, the project team co-led by Associate Professor, Dr. Nguyen Ngoc Dinh, Head of the Department of Physics, University of Natural Sciences – Hanoi National University, has built a fully Vietnamese-owned printer system and created artificial blood vessels.

Associate Professor Dinh said that the group’s journey to develop a biological 3D printer system originated from a discussion with Associate Professor, Doctor of Medicine Do Xuan Hai, Head of the Department of Practical and Experimental Surgery – Military Medical Academy, about the urgent need in organ transplantation.

Statistics from the Ministry of Health show that Vietnam currently estimates that about 8,000-9,000 people need kidney transplants, 10,000 people need liver transplants, and 1,000 people need heart transplants. The number of patients waiting for corneal transplants also reaches thousands. These numbers increase each year, as the source of donated organs cannot keep up with demand.

There are similar problems around the world, while organ donation is no longer a sustainable solution. Scientists are looking for alternative solutions, in which 3D bioprinting is a technology being explored.

Believing that domestic capacity can fully pursue this technology, Associate Professor Dinh along with colleagues at the Department of Biology – University of Natural Sciences, Vinmec Research Institute of Stem Cell and Gene Technology – VinUni and the Department of Practical and Experimental Surgery – Military Medical Academy built an interdisciplinary project to develop a biological 3D printer system.

In particular, the Department of Physics researched the printing system, the Department of Biology and VinUni developed printing inks, and the Military Medical Academy put the final product, artificial blood vessels, into testing on mice.

Dr. Than Thi Trang Uyen, VinUni, a member of the team in charge of biological materials, said that it is not difficult to import computer systems, but so the domestic team only plays the role of operator for closed ecosystems of foreign suppliers, with many components and proprietary and secret formulas. “Mastering the underlying technology aims to deeply improve specific research in Vietnam,” Dr. Uyen explained the reason the group pursued technology decoding.

Accordingly, the team spent nearly 2 years testing many core components of the technology, including printing ink or the formula for cell spheres, which are considered “living bricks”. “The goal is to create stem cell spheres that are uniform in both size and cell density so that the printer can operate stably, without clogging or misalignment of coordinates,” Dr. Uyen recounted.

The team said that each “living brick” is a sphere of cells, cultured from stem cells. A robotic arm attaches and drops these spheres onto a platform made up of microscopic needles, according to the programmed design and coordinates. After being pinned on the spike, over time, the cell spheres will self-assemble into complete tissue. Once the tissue is stable enough, the entire structure will be retracted and the small holes will close on their own through cell migration, a mechanism similar to when the body heals a wound.

Instead of 3D printing using conventional extrusion, the team aims to master the printing method on the Kenzan needle table, with the advantage of creating structures with cell density and extracellular matrix equivalent to natural tissue, helping to increase biocompatibility after transplantation. This is also the same method as the most advanced 3D organ printing projects in the world today.

According to Dr. Uyen, the solution has been implemented by many research groups around the world, but a series of details related to formulas and techniques require trial and error to find.

Ink, environment and mechanical systems continue to be problems for the physics group. The Kenzan needle table requires needles to be arranged with high density and precision at 0.001 mm. The needle must be hard enough, the surface must be processed absolutely smooth so as not to damage or break the structure of the cell spheres when inserted, and must also ensure biological inertness so that the cells are not denatured upon contact.

Unlike extrusion printing, the Kenzan method requires the robot to pick up each cell sphere and accurately insert it into each needle according to programmed 3D coordinates. This process requires a precise mechanical system with extremely sensitive response, controlling the suction and release force just enough to not crush the very fragile living cells.

“Many micro-precision mechanical components or high-sensitivity sensors are almost not available on the market, the team has to manufacture them themselves or customize them from many different sources to integrate into a complete system,” Associate Professor Dinh said.

Potential to create skin, cartilage, cornea and drug testing tissue

The research team has succeeded in printing and grafting 3D printed blood vessels, cultured from human umbilical cord mesenchymal stem cells, into the abdominal aorta and lower kidney of Wistar rats. Initial results show that blood vessels achieve a high level of biocompatibility, with little risk of rejection – the most common problem in organ transplantation. All experimental mice maintained stable blood circulation and blood pressure, had the ability to walk and exercise normally, and test indicators had no negative differences.

However, Associate Professor Dinh said that 3D printing cannot immediately solve the problem of organ scarcity, but is a research direction to help access and master a potential core technology.

According to Associate Professor Hai, with the technology, infrastructure and needs of the Vietnamese health sector, the first 3D bioprinted products that create a real impact will not be complex internal organs, but thin tissue structures, complex non-vascular tissues or simulation models for drug testing.

The most feasible direction for clinical application in the near future is to print pieces of ear cartilage for children with birth defects, knee cartilage for elderly people with osteoarthritis, or cartilage shaped according to defects from cartilage stem cells. In addition, this 3D bioprinting technology can create cultured epidermal skin structures from the patient’s own stem cells to cover the wound.

The cornea was also assessed by the research team as highly viable and desirable for development. The need for corneal transplants in Vietnam is large due to injuries caused by work accidents, diseases or corneal scarring, while the source of corneas depends entirely on donations, which are scarce.

Legal corridor – application barrier

Associate Professor Dinh said that up to now the biggest barrier to applying this technology is the legal framework. Due to the use of living stem cells, 3D bioprinted products are considered living tissues or special biological drugs, not inert materials like artificial bone printing. Currently, Vietnam and the world do not have a clear set of standards and testing procedures for this personalized product.

The traditional medical approval process relies on extensive clinical testing of thousands of homogeneous samples to demonstrate safety. But the nature of 3D bioprinting is individualization for each patient, organ structure and stem cell source, posing the problem of licensing management for products that are created in a different version each time.

Long-term biological risks are also important to note. Stem cells, after being printed and transplanted into the body, are at risk of mutating incorrectly or, more seriously, creating tumors.

“Proving and absolutely controlling this safety to get clinical approval from legal authorities is a barrier that takes a lot of time, maybe 5 to 10 years,” Associate Professor Hai said.

While the clinical direction still has many regulatory hurdles, 3D bioprinting to create test models for the pharmaceutical industry will create an early economic impact. In the immediate future, this technology will aim to print miniature human tissue structures such as liver tissue, kidney tissue or cancer tumor models of Vietnamese patients.

Domestic research institutes and pharmaceutical enterprises can use these living tissues to test drug toxicity, replacing animal testing, which has limited ethics and accuracy. This method also helps to screen personalized drugs, testing which chemotherapy regimen is most effective on tumors cultured from each patient’s cells before infusing the drug into the body.

“With the companionship of leading medical centers and hospitals, Vietnam has the opportunity to establish testing processes on living tissue to serve the domestic pharmaceutical industry,” Associate Professor Dinh expected.