Nanoengineered Bioink could simplify printing of bioburdened 3D gels

Recent news from Texas A&M University suggests that the well-documented story of 3D bioprinted structures may need to be revised. These stories say that 3D bioprinted structures do a poor job of incorporating therapeutic proteins. But it now appears that these structures can be easily loaded with therapeutic proteins that can be sequestered for extended periods of time and then gradually released to control cellular function.

3D bioprinting is emerging as a promising method for the rapid fabrication of cell-containing constructs for the design of novel, healthy, functional tissues. However, one of the main challenges of 3D bioprinting is the lack of control over cell function. Growth factors are a special class of proteins that control cell fate and function. However, these growth factors cannot be easily incorporated into 3D bioprinted structures for extended periods of time.

In a recent study conducted at Texas A&M, researchers in the laboratory of biomedical engineer Akhilesh K. Gaharwar, Ph.D., formulated a bioink to facilitate the printing of 3D structures capable of releasing protein therapeutics at precise locations. The researchers’ findings were recently published in Advanced Healthcare Materials under the title “3D Printing Therapeutic Proteins Using Nanoengineered Bioinks to Control and Direct Cell Migration.”

“Addition of 2D nanosilicates to poly(ethylene glycol)-dithiothreitol (PEGDTT) resulted in the formation of shear-thinning bioinks with high printability and structural fidelity,” the paper said. The authors of the paper are introduced in detail. “The mechanical properties, swelling kinetics and degradation rate of the 3D printed structures can be tuned by varying the PEG:PEGDTT ratio and the nanosilicate concentration.”


Essentially, the Texas A&M team found a way to print a hydrogel, a 3D structure that can absorb and retain large amounts of water, to insulate therapeutic proteins. The team used a bioink that incorporates polyethylene glycol (PEG), an inert polymer, which is great for tissue engineering because it doesn’t stimulate the immune system.

Typical PEG polymer solutions have low viscosity, which can complicate 3D printing. To overcome this limitation, the team combined PEG polymers with nanoparticles. This combination resulted in a novel bioink hydrogel that supports cell growth and has enhanced printability compared to the polymer hydrogel itself.

While experimenting with 3D-printed constructs loaded with a pro-angiogenic therapeutic, Texas A&M scientists observed sustained release of the therapeutic, promoting rapid migration of human endothelial umbilical vein cells. “This method of designing bioactive inks to control and direct cellular behavior could be used to design 3D complex tissue structures for regenerative medicine,” the scientists assert.

This new technology is based on a nanoclay platform developed by Gaharwar for precise deposition of protein therapeutics. This bioink formulation has unique shear-thinning properties to infuse the material. The material then quickly stops flowing, solidifies and stays in place, which is highly desirable for 3D bioprinting applications.

“This formulation using nanoclay chelates therapeutics that increase cell viability and proliferation,” said Texas A&M biomedical engineer Charles W. Peak, Ph.D., lead author of the paper. “In addition, bioactive therapeutics’ Prolonged delivery can improve cell migration within the 3D printed scaffolds and facilitate rapid angiogenesis of the scaffolds.”

Extending the use of therapeutic drugs can also reduce overall costs by lowering the concentration of the therapeutic drug and minimizing adverse side effects associated with supraphysiological doses, Gaharwar said. “Overall, this study provides proof-of-principle 3D-printed protein therapy that can be used to control and direct cellular function,” he said.

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