Hydrogel injection molding is a viable alternative to three-dimensional bioprinting, offering efficiency, scalability and reproducibility for even complex 3D cell-laden geometries and high-throughput cell product manufacturing.

Time savings is a huge benefit, Jessica D. Weaver, PhD, assistant professor, Arizona State University, tells GEN. “Current extrusion-based systems generated a single 3D geometry in about five to 20 minutes…with up to another five minutes needed for set-up. In contrast, injection molding with a single mold takes one minute or less for a comparable geometry.” A robotics system could do that even faster. “We predict injection molding could be at least 5–20 times faster than current bioprinting methods.”

The challenge is to generate 3D structures with void spaces. “Injection molding has slightly less capability to generate 3D structures with void spaces in the z direction than bioprinting,” she says. This is a challenge for bioprinting, too, she adds, because of the buildability of soft hydrogels.

That said, “Injection molding is an excellent alternative. It has the potential to be much more high-through relative to printing techniques and will be easier to scale, automate, and implement using good manufacturing processes.”

Weaver and colleagues evaluated the process and identified suitable hydrogels in a recent paper. Working with agarose, alginate, and polyethylene glycol (PEG) hydrogels, they used lower viscosity solutions to reduce static pressure inside the injection molds and thus increase injection speeds and enable smaller mold features without increasing pressure. To extend gel times, they extended hydrogel crosslinking times for agarose hydrogel; increased pH for PEG-maleimide hydrogels; and liberated calcium from the calcium carbonate for alginate hydrogels.

Their objective was to use a spiral injection mold to encapsulate human primary islet cells in a way that enhanced oxygenation and cell retrievability. They found that agarose- and alginate-encapsulated cells were comparable in terms of viability—90 and 87 percent, respectively—and maintained that viability at least 24 hours. Viability for the 1 mm agarose spiral, however, declined from 90 to 84 percent during that timeframe.

“Biomanufacturing of cell products is in its infancy,” Weaver says. As it matures, manufacturers will need “to make biomaterial-based combination products in a high-throughput, scalable manner in line with automated cell manufacturing systems.

Hydrogel injection molding offers the means to do this in a way that bioprinting does not currently offer, and reduces the labor required to fabricate combination products (cells + biomaterials), increases process automation, increase reproducibility, and reduces the time to fabricate each product.”