Nanoengineered Bioink Eases Printing of Biologic-Loaded 3D Gels
Stop the presses! Late-breaking news from Texas A&M University indicates that well-documented stories about 3D-bioprinted structures may need to be emended. These stories say that 3D bioprinted structures do a poor job of incorporating therapeutic proteins. But now it appears that these structures can be readily loaded with therapeutic proteins, which can be sequestered for prolonged periods—and released gradually to control cell function.
3D bioprinting is emerging as a promising method for rapidly fabricating cell-containing constructs for designing new, healthy, functional tissues. However, one of the major challenges in 3D bioprinting is lack of control over cellular functions. Growth factors, which are a special class of proteins, can direct cellular fate and functions. However, these growth factors cannot be easily incorporated within a 3D-bioprinted structure for a prolonged duration.
In a recent study conducted at Texas A&M, researchers in the laboratory of biomedical engineer Akhilesh K. Gaharwar, PhD, formulated a bioink to facilitate the printing of 3D structures capable of releasing protein therapeutics at precise locations. The researcher’s findings were recently published in Advanced Healthcare Materials, in an article titled, “Printing Therapeutic Proteins in 3D using Nanoengineered Bioink to Control and Direct Cell Migration.”
“The addition of 2D nanosilicates to poly(ethylene glycol)‐dithiothreitol (PEGDTT) results in formation of shear‐thinning bioinks with high printability and structural fidelity,” detailed the article’s authors. “The mechanical properties, swelling kinetics, and degradation rate of 3D-printed constructs can be modulated by changing the ratio of PEG:PEGDTT and nanosilicates concentration.”
Essentially, the Texas A&M team found a way to print hydrogels—3D structures that can absorb and retain considerable amounts of water—that can sequester therapeutic proteins. The team used a bioink that incorporates an inert polymer, polyethylene glycol (PEG), which is advantageous for tissue engineering because it does not provoke the immune system.
Typical PEG polymer solutions have low viscosity, which complicates 3D printing. To overcome this limitation, the team combined PEG polymers with nanoparticles. The combination led to novel bioink hydrogels that can support cell growth and may have enhanced printability compared to polymer hydrogels by themselves.
While experimenting with a 3D-printed structure that had been loaded with pro‐angiogenic therapeutics, the Texas A&M scientists observed sustained release of the therapeutics, which promoted the rapid migration of human endothelial umbilical vein cells. “This approach to design biologically active inks to control and direct cell behavior,” the scientists asserted, “can be used to engineer 3D complex tissue structure for regenerative medicine.”
This new technology, based on a nanoclay platform developed by Gaharwar, can be used for precise deposition of protein therapeutics. This bioink formulation has unique shear-thinning properties that allow the material to be injected. Then the material quickly stops flowing, cures, and stays in place, which is highly desirable for 3D bioprinting applications.
“This formulation using nanoclay sequesters the therapeutic of interest for increased cell activity and proliferation,” said Charles W. Peak, PhD a biomedical engineer at Texas A&M and the lead author of the paper. “In addition, the prolonged delivery of the bioactive therapeutic could improve cell migration within 3D printed scaffolds and can help in rapid vascularization of scaffolds.”
Gaharwar said the prolonged delivery of the therapeutic could also reduce overall costs by decreasing the therapeutic concentration as well as minimizing the negative side effects associated with supraphysiological doses. “Overall, this study provides proof of principle to print protein therapeutics in 3D that can be used to control and direct cell functions,” he said.