Introduction to Antarctic Bears: In the manufacture of biological tissues, 3D printed ears are a hot topic for researchers. Recently, new progress has been made in this field.
On June 15, 2020, Antarctic Bear learned from foreign media that researchers from Sichuan University of China, Ghent University of Belgium and University of California San Diego developed a method to print human ears in 3D on the inside of human body.
The research team has newly developed a 3D printing technology based on digital near infrared (NIR) photopolymerization (DNP), which can realize noninvasive 3D biological printing of tissue constructs in vivo. This new method can allow doctors to repair human ears damaged by sports injuries or accidents, and opens up a new way of non-invasive medicine for 3D printing research.
Delta Non-invasive 3D Bioprinting Schematic Based on DNP
The customized CAD model data is sent to DMD chip through control computer. 980nm near-infrared light with optical pattern is projected onto biological ink through optical lens and tissue to non-invasively produce living tissue in human body. The biological ink contains UCNP@LAP nano initiator, which can convert near infrared light into 365nm light and then cause monomer polymerization.
Tissue Manufacturing Using Bioprinting Technology
In recent years, bio-printing technology has been used to create personalized structures for a series of medical applications, especially in regenerative medicine. Using inkjet, extrusion, laser direct writing and photo-curing 3D printing technologies, scientists have been able to produce living organs and tissues. Many of these in vivo applications require invasive surgery or in situ 3D printing on exposed wounds. In addition, for internal injuries under the skin, the operation to expose the wound surface may damage the surrounding tissues and cause secondary injuries.
Researchers have developed a 3D printing process to replace DLP, enabling them to make tissue-covered bio-ink into customized products, including in-situ living tissue construction. Previous methods have used DLP for multi-tissue reconstruction or repair, including spinal cord, peripheral nerve and vascular injuries. Traditionally, ultraviolet (UV) or blue light is used to assist biological printing through photopolymerization, but these are difficult to be used as non-invasive manufacturing tools because of their poor tissue permeability.
In order to have the ability to penetrate deep tissues, researchers have developed a method based on near infrared (NIR) light instead of ultraviolet or blue light. Controlled-release drugs traditionally used for patients can non-invasively manufacture tissue-covered bio-ink into structured products by precisely controlling near-infrared induced high-efficiency photopolymerization. On the basis of designing the digital near infrared polymerization (DNP) process, the research team has created a noninvasive 3D bio-printing system in vivo.
Making Human Ears with 3D Bioprinting Technology
Researchers’ method includes creating a computer aided design (CAD) model and dynamically generating digital near infrared through connected digital micromirror device (DMD) chips. Then, infrared light is projected to induce the locally injected biological ink to polymerize layer by layer in a non-invasive manner. Commonly used biocompatible hydrogel monomers, such as gelatin methacryloyl (GelMA), have been proved to be compatible with this polymerization under near infrared irradiation. Once the biomaterial is activated, the images are sequentially fed into the computer.
Tests show that DNP process can quickly print GelMA derived hydrogel, and it takes about 15 seconds to print a layer of 200μm thick tissue. In order to evaluate the capability of this method, a tricyclic microstructure with decreasing width from 200 to 100μm was fabricated using DNP process. The double-layer microstructure has precise and customized 3D features, such as flower-shaped, cake-shaped and a truss structure. The fabrication in vitro proves the capability of this technology.
△ Before making 3D printed ears, researchers made a series of complicated 3D microstructures with pictures from Science Advances.
(a) Structural images taken by scanning electron microscope (SEM), including tricyclic microstructure with decreasing width, flower shape, pellet shape, round cake shape and a truss structure, with a scale of 200 μ m. (b) A schematic diagram of printing setup for estimating tissue permeability, with biological ink deposited under the skin or muscle. (c) The image of the ring structure printed by DNP process under the three conditions of biological ink on the surface, covering under the skin and under 0.5mm thick muscle. Scale: 0.5 cm.
Researchers covered a 0.5mm thick piece of pig muscle tissue in bio-ink to simulate non-invasive 3D bio-printing in vivo. Using near-infrared light, the research team can stimulate the patterned emission of nano-initiators in biological ink and induce polymerization. When the process was tested in laboratory mice, it did not affect the surrounding tissues, and the mice had complete tissue structure and no obvious inflammation and abnormal defects. Three types of structures, including triangular, cross-shaped and two-layer cake hydrogel constructs, have been successfully printed noninvasively in vivo by DNP process, indicating that the process can realize noninvasive 3D biological printing in vivo.
Researchers used the same technique to create a customized ear-shaped construct containing chondrocytes. After printing, the cells of the ear have good viability. After cultured in vitro for 7 days and one month, the ear shape of the constructed body has been maintained. As a proof of concept for non-invasive 3D bioprinting, the auricular tissue provides a broad application prospect in future tissue regeneration and auricle reconstruction.
Previous 3D Bioprinting Methods
Bioprinting technology has been used in rapid prototyping manufacturing to produce a series of living organs and tissues for implantation.
The Russian Biotechnology Research Laboratory 3D Bioprinting Solutions has 3D bioprinted bone tissue under zero gravity on the International Space Station (ISS). Using the laboratory’s magnetic 3D bio-printer Organ.Aut, the project hopes to create bone implants for astronauts during long-term interstellar exploration.
Scientists from Carnegie Mellon University (CMU) in Pennsylvania used a new 3D bioprinting method to build functional parts of the human heart, August 2019. Using free-form reversible embedded suspended hydrogel (FRESH) technology, the team was able to print collagen from small blood vessels, valves and beating ventricles in 3D.
Aspect Biosystems, a 3D bioprinting technology company, announced its cooperation with Maastricht University (UM) in the Netherlands in January 2019. The focus of the project is to develop viable kidney tissue for medical testing.
The research results of the researchers are detailed in their paper “Non Invalidity in Vivo 3D Bioprinting” published in the journal Science Advances. The study was conducted by yuwenchen, jiu mengzhang, xuanliu, shuaiwang, jietao, yulan huang, wenbiwu, yang li, kai zhou, xiaweiwei, shaochenchen, xiang li, Xue wenxu, ludwig cardon, zhiyong qin and malingou.
Compiled by: 3 dprintinggindustry