Bioprinting Organs: Researchers Create Less Expensive Bioink Based in 3D Printed Gelatin Hydrogels

3D printed hydrogels have had many different applications in the medical field, from delivering precise doses of medicine and making custom meniscus implants to engineering tissue so that in the future, we can create artificial, transplantable organs. Two years ago, a team of researchers with the Queensland University of Technology were working to develop stiffer and more robust hydrogels so they could successfully harvest human cells by using a 3D printing process known as melt electrospinning direct writing to reinforce gelatin methacrylate (GelMA) hydrogels with porous polycaprolactone (PCL) fiber scaffolds. GeIMA is used often in the medical field because it allows for matrix deposition of cells, and now researchers at the University of British Columbia (UBC) Okanagan campus are among those taking a closer look at GeIMA.

The researchers have created a better, less expensive bioink, made of living cells and based in GeIMA, that could offer more efficient, cheaper fabrication of human organs and tissues in the field of regenerative medicine. They are using 3D printing and other techniques to create biomaterial products which are able to function right along living cells, and GeIMA serves as a major bioprinting building block.

The UBC team created two different types of GeIMA hydrogels for their research – one from cold-water fish skin and another from cold-soluble gelatin, which is often used in culinary applications. Then they analyzed the biological and physical properties of the new hydrogels and compared them to porcine skin GeIMA. While the fish skin GeIMA was a solid choice, the team determined that the cold-soluble gelatin, which dissolves without heat and is three times cheaper than porcine skin gelatin, was the best candidate for future 3D printing of organs, as it can form healthy tissue scaffolds and was thermally stable at room temperature.

“A big drawback of conventional hydrogel is its thermal instability,” explained Keekyoung Kim, an assistant professor in the university’s School of Engineering who led the research team. “Even small changes in temperature cause significant changes in its viscosity or thickness. This makes it problematic for many room temperature bio-fabrication systems, which are compatible with only a narrow range of hydrogel viscosities and which must generate products that are as uniform as possible if they are to function properly.”

The UBC researchers published a paper on their work, titled “Comparative study of gelatin methacrylate hydrogels from different sources for biofabrication applications,” in last month’s issue of the Biofabrication journal; co-authors include Zongjie Wang, Zhenlin Tian, Fredric Menard, and Kim.

The abstract explains, “Gelatin methacrylate (GelMA) hydrogel is a promising bioink for biofabrication applications due to its cost-effectiveness, ease of synthesis and biocompatibility to allow cell adhesion. However, the GelMA synthesized from a widely used porcine skin gelatin has a thermal gelation problem at room temperature. Here, we present thermally stable GelMA hydrogels at room temperature while maintaining the mechanical and biological properties comparable to porcine GelMA. The novel GelMA hydrogels were synthesized from fish skin and cold soluble gelatin. We systematically characterized the properties of the GelMA hydrogels from different sources. The properties include the degree of methacrylation, compressive Young’s modulus, mass swelling ratio, viscosity, and cell adhesion and proliferation in 2D and 3D microenvironments. It has been found that the cold soluble GelMA was comparable to the porcine skin GelMA but could offer low viscosity and thermal stability at room temperature. We performed a droplet generation experiment to demonstrate the benefit of using the cold soluble GelMA for biofabrication. The cold soluble GelMA showed a more reliable and stable droplet fabrication process. Taken together, the cold soluble GelMA is a promising bioink solution and may greatly benefit the research in biofabrication.”

UBC Okanagan’s Keekyoung Kim

In addition, the team demonstrated that its cold-soluble GeIMA hydrogel is able to make consistently uniform droplets, which makes it a very good 3D bioprinting option. According to Kim, this development could “accelerate advances in regenerative medicine.”

“We hope this new bio-ink will help researchers create improved artificial organs and lead to the development of better drugs, tissue engineering and regenerative therapies. The next step is to investigate whether or not cold-soluble GelMA-based tissue scaffolds are can be used long-term both in the laboratory and in real-world transplants,” said Kim.

The UBC researchers aren’t the only ones studying GeIMA and 3D printing technology: a team with RWTH Aachen University Hospital in Germany also recently published a paper in the Biofabrication journal. The Aachen University researchers are studying how GeIMA-collagen blends promote angiogenesis (when new blood vessels form from pre-existing vessels) and allow for drop-on-demand 3D printability.

According to the abstract, “Till date, several hydrogel blends have been developed that allow the in vitro formation of a capillary-like network within the gels but comparatively less effort has been made to improve the suitability of the materials for a 3D bioprinting process. Therefore, we hypothesize that tailored hydrogel blends of photo-crosslinkable gelatin and type I collagen exhibit favorable 3D drop-on-demand printing characteristics in terms of rheological and mechanical properties and that further capillary-like network formation can be induced by co-culturing human umbilical vein endothelial cells and human mesenchymal stem cells within the proposed blends.”

The team built a custom 3D drop-on-demand bioprinter, to measure dispensable hydrogel droplet volumes. The researchers report that capillary-like structures were formed in 3D printable GeIMA-collagen hydrogels, and determined that the blend showed good biological and rheological properties that are well-suited to manufacture pre-vascularized tissue replacement through 3D bioprinting.

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