KAUST scientists develop automated 3D bioprinting process for peptide-based hydrogels

Researchers from the King Abdullah University of Science and Technology (KAUST) have developed a new method of 3D printing hydrogel scaffolds based on ultrashort peptides.

Peptides are short chains of amino acids, which form the building blocks of proteins. The researchers used ultrashort peptides as the basis of their newly developed ink which can be 3D printed to form hydrogels containing cells. 

Led by KAUST bioengineer Charlotte Hauser, the team are seeking to address challenges surrounding shape stability in 3D printed hydrogels without the use of harsh chemicals or ultraviolet light that threaten cell survival.

“It’s challenging to find a cell-friendly biomaterial that supports long-term cell survival and is also printable,” said KAUST PhD student Hepi Hari Susapto. “Our bioinks made from self-assembling ultrashort peptide hydrogels efficiently address this challenge.”

The newly developed bioprinting technique has the potential to revolutionize tissue engineering and regenerative medicine. Photo via KAUST.
The newly developed bioprinting technique has the potential to revolutionize tissue engineering and regenerative medicine. Photo via KAUST.

3D bioprinting advances

3D printed cell-laden structures hold great potential for human tissue and organ transplant, however the technology is still in its nascent stage and faces hurdles such as bioink development, limited print speeds, and print resolution before wider adoption can be achieved. Saying this, there have been important developments in this area over the past year which show promise in advancing 3D bioprinting. 

For instance, University of Buffalo scientists have developed a rapid new bioprinting method that could bring fully-printed human organs closer to reality, and US 3D printer OEM 3D Systems is set to ramp up its regenerative medicine activities after experiencing a breakthrough with its Print to Perfusion bioprinting platform

Most recently, researchers from Lund University developed a new 3D printable bioink that enabled them to create human-sized airways that support new cell and blood vessel growth. Although lung tissue formed the initial focus of the study, the bioink has the potential to be adapted for any tissue or organ type.

3D printing peptides

To start with, the KAUST researchers designed three peptides using different combinations of the amino acids isoleucine, lysine, phenylalanine, and cyclohexylalanine, in order to create a printable bioink. 

The team then used a triple-inlet nozzle to 3D print their hydrogel structures. The peptide bioink was fed into one inlet, a buffer solution into another, and cells were added through a third. This method enabled the peptide ink to gradually mix with the buffer solution then combine with the cells at the nozzle’s outlet. Once the ink is ejected from the nozzle, it instantly solidifies and captures the cells within its structure. 

The team printed hydrogel cylinders up to four centimeters tall, as well as a human-like ‘nose’, which were all capable of retaining their shapes. The cells added to the hydrogel scaffolds included human fibroblasts, human bone marrow mesenchymal stem cells, and mouse brain neurons, which all survived and proliferated well within the structures. The bone marrow cells were also encouraged to differentiate inside the printed scaffold into elastic tissue resembling cartilage over the course of four weeks. 

Going forwards, the researchers will look to further alter the surface chemistry of their developed bioinks in order to make them more closely resemble the cell environment within the human body.

“Our next step is to bioprint 3D disease models and miniature organs for high-throughput drug screening and diagnosis,” said Hauser. “These could help reduce the time and cost of searching for more effective and personalized drugs.”

Further information on the study can be found in the paper titled “Ultrashort peptide bioinks support automated printing of large-scale constructs assuring long-term survival of printed tissue constructs”, published in the Nano Letters journal. The paper is co-authored by H. Susapto, D Alhattab, S. Abdelrahman, Z Khan, S. Alshehri, K. Kahin, R. Ge, M. Moretti, A. Emwas, and C. Hauser.

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Featured image shows the newly developed bioprinting technique has the potential to revolutionize tissue engineering and regenerative medicine. Photo via KAUST.