A better, cheaper bioink for biofabrication

Cell adhesion and proliferation in 2D cultures with GelMA hydrogels from different sources
Cell adhesion and proliferation in 2D cultures with GelMA hydrogels from different sources

A new bioink that may enable the more efficient and inexpensive fabrication of tissues and organs — and ultimately accelerate advances in regenerative medicine — has been synthesized by researchers at the University of British Columbia's Okanagan campus.

To create biologically functional products in the lab, scientists combine living cells, bioactive molecules and biomaterials into organized structures. One such biomaterial is gelatin methacrylate (GelMA), a chemically modified hydrogel that serves as a bioink and building block in bioprinting and bioassembly processes.

As reported in the latest issue of Biofabrication, the UBC team analyzed the physical and biological properties of three different GelMA hydrogels — porcine skin, cold water fish skin and cold soluble gelatin — and found that hydrogel made from cold soluble gelatin (gelatin which dissolves without the application of heat) shares all the positive attributes of porcine skin GelMA, the most commonly used hydrogel, but not its major weakness.

“A big drawback of conventional hydrogel is its thermal instability: even small changes in temperature cause significant changes in its viscosity, or thickness,” says Keekyoung Kim, a professor of engineering at UBC who supervised the study. “This makes it problematic at room temperature for many biofabrication systems, which are compatible with only a narrow range of hydrogel viscosities and must generate products that are as uniform as possible if they are to function properly.”

Due to its thermal instability, porcine skin GelMA is prone to clogging the printheads of inkjet bioprinters and tends to form inconsistent structures and microdroplets (or fails to form droplets at all) when used at temperatures between 20 and 30 degrees Celsius (68 to 86 degrees Fahrenheit). For conventional hydrogel to be useable, its temperature needs to be carefully maintained at or above 35 degrees Celsius (95 degrees Fahrenheit) for the duration of biofabrication processes — a costly, complex capability that most biofabrication systems do not have.

​  Thermal gelation of different GelMA hydrogels at various temperatures  ​
Thermal gelation of different GelMA hydrogels at various temperatures

So the UBC researchers created two new hydrogels — one from fish skin gelatin, another from cold soluble gelatin — and compared their properties to those of porcine skin GelMA. Although fish skin GelMA had some benefits, cold soluble GelMA was the top performer overall: not only could it form robust tissue scaffolds — in both two-dimensional and three-dimensional cultures, cells adhered to and proliferated on them in numbers comparable to those of porcine skin GelMA — but it was also thermally stable at room temperature.    

With its reduced sensitivity to changes in ambient temperature and relatively low viscosity at higher temperatures, cold soluble GelMA is ideal for use in various biofabrication applications, including the production of microdroplets for bioassembly. The UBC team demonstrated that cold soluble GelMA produces consistently sized microdroplets at temperatures where porcine skin GelMA is an unworkable gel, or otherwise forms irregular droplets.

“We hope this new bioink will help researchers create improved artificial organs and lead to the development of better drugs and regenerative therapies,” says Kim.

Three times cheaper than porcine skin gelatin, cold soluble gelatin is used primarily in culinary applications, where it serves as a gelatin substitute when heat is either not required or would otherwise interfere with food preparation. The researchers are now investigating whether or not cold soluble GelMA-based tissue scaffolds are viable for long-term use both in the laboratory and as in vivo transplants.