Scientists create new biocompatible bio-ink to 3D print artificial organs

The new temperature method is based on a "poly(organophosphazene)-based temperature-sensitive hydrogel."
Mrigakshi Dixit
Representational image: Researcher getting 3D bioprinter ready to 3D print cells.
Representational image: Researcher getting 3D bioprinter ready to 3D print cells.


3D bioprinting is an emerging field of regenerative medicine that holds great promise for Earthlings and future space travelers. 

Recently, a team of researchers developed a biocompatible and biodegradable bio-ink. Scientists from the Korea Institute of Science and Technology (KIST) have created a new bio-ink that uses temperature to harden and bind the printed structure. As a result, it is more biocompatible with tissues than existing bio-inks. 

The development of the new bio-ink

Typically, to bioprint an artificial organ bio-ink needs to be firmed up using various techniques, such as UV light or chemical crosslinking. 

The method, called photocuring, uses ultraviolet light to harden the substrate. However, UV light can damage the cells’ DNA while creating an artificial organ or tissue. Another method, known as chemical crosslinking, employs a chemical reagent (crosslinker) to achieve bioprint. Both of these techniques may cause cytotoxicity, which means cell damage and a reduction in the regeneration power required for the printed organ to function correctly. 

Meanwhile, this temperature method is based on a "poly(organophosphazene)-based temperature-sensitive hydrogel." This substance is commonly found in liquid form and functions at low temperatures. This property can felicitate 3D printing to efficiently achieve the physical stability of structures at body temperature, thereby eliminating the requirement of photocuring or chemical crosslinking.

Simply put, this new method allows bio-ink to harden in relation to body temperature, making it much more biocompatible for tissue regeneration applications.

The researchers also demonstrated that the newly developed bio-ink could be combined with growth factors to stimulate cell growth. To put this application to test, the researchers created a 3D scaffold out of bio-ink and growth proteins, which they implanted into a rat's damaged skull. Normal bone regeneration was seen in the results.

"As the bio-ink developed this time has different physical properties, follow-up research to apply it to the regeneration of other tissues besides bone tissue is being conducted, and we expect to finally be able to commercialize bio-ink tailored to each tissue and organ," said Dr. Song Soo-Chang of KIST, in a press statement. The study can be found in the journal Small.

The science of 3D bioprinting

Living human organs are difficult to replicate due to the presence of numerous complex structures such as microchannels, tissue networks, blood vessels, nerves, and more.

To create three-dimensional living structures, this technology uses a layer-by-layer approach. The bioprinters use super-fine needlepoints and bio-inks made of healthy living cells to achieve precise printing. 

To bioprint an entire liver, for example, a large number (up to billions) of healthy cells are required. Furthermore, these bio-inks are combined with biochemical components in order to mimic living tissue and promote cell growth. Another essential component of the bio-ink is hydrogels, which are water-rich molecules that act as glue.

Bioprint models could be used in space to study the effects of microgravity, radiation, and even impact on astronaut's bone tissues, to name a few. Scientists envision a future in which this potentially life-saving technology will be able to travel to the Moon and beyond. 

In the near future, 3D bioprint models can potentially improve medical research, education, and training. Without using animal testing models, miniature tissue models can be used to test drug efficacy. The ultimate goal is to contribute to the resolution of the world's organ shortage crisis.

Study abstract:

Three-dimensional (3D) bioprinting, which is being increasingly used in tissue engineering, requires bioinks with tunable mechanical properties, biological activities, and mechanical strength for in vivo implantation. Herein, a growth-factor-holding poly(organophosphazene)-based thermo-responsive nanocomposite (TNC) bioink system is developed. The mechanical properties of the TNC bioink are easily controlled within a moderate temperature range (5–37 °C). During printing, the mechanical properties of the TNC bioink, which determine the 3D printing resolution, can be tuned by varying the temperature (15–30 °C). After printing, TNC bioink scaffolds exhibit maximum stiffness at 37 °C. Additionally, because of its shear-thinning and self-healing properties, TNC bioinks can be extruded smoothly, demonstrating good printing outcomes. TNC bioink loaded with bone morphogenetic protein-2 (BMP-2) and transforming growth factor-beta1 (TGF-β1), key growth factors for osteogenesis, is used to print a scaffold that can stimulate biological activity. A biological scaffold printed using TNC bioink loaded with both growth factors and implanted on a rat calvarial defect model reveals significantly improved bone regenerative effects. The TNC bioink system is a promising next-generation bioink platform because its mechanical properties can be tuned easily for high-resolution 3D bioprinting with long-term stability and its growth-factor holding capability has strong clinical applicability.

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