In a major 3D printing story that attracted the attention of Newsweek (a magazine also known for writing articles claiming that 3D printing is over), a nano 3D printing technology generally known as Two-Photon Photopolymerization (2PP) was used by Brenda Ogle, an associate professor of biomedical engineering at the University of Minnesota-Twin Cities, to create a patch that doctors could apply to help a patient heal in case of myocardial infarction (i.e. heart attack).
Conventional three-dimensional (3D) printing techniques cannot produce structures of the size at which individual cells interact. In this study, the scientists used “multiphoton-excited, 3-dimensional printing” (MPE-3DP), which is the name they gave to their own version of 2PP, to generate a native-like, extracellular matrix (ECM) scaffold with submicron resolution, and then seeded the scaffold with cardiomyocytes (CMs), smooth-muscle cells (SMCs), and endothelial cells (ECs) that had been differentiated from human induced-pluripotent stem cells (iPSCs) to generate a human, iPSC-derived cardiac muscle patch (hCMP), which was subsequently evaluated in a murine model of myocardial infarction (MI).
You can view a detailed explanation of multiphoton 3D printing technologies here. While these technologies have been developed internally at several universities, the only company currently offering a commercial systems is Germany based Nanoscribe with its Photonic Professional GT system. multiphoton 3D printing can enable resoutions of just a few tens of nanometers and it is also unique in that it can produce objects polymerizing from several directions at once, not just on the surface. This also means it does not create layers.
Methods and Results
The scaffold was seeded with ~50,000 human, iPSC-derived CMs, SMCs, and ECs (in a 2:1:1 ratio) to generate the hCMP, which began generating calcium transients and beating synchronously within 1 day of seeding; the speeds of contraction and relaxation and the peak amplitudes of the calcium transients increased significantly over the next 7 days. When tested in mice with surgically induced MI, measurements of cardiac function, infarct size, apoptosis, both vascular and arteriole density, and cell proliferation at week 4 after treatment were significantly better in animals treated with the hCMPs than in animals treated with cell-free scaffolds, and the rate of cell engraftment in hCMP-treated animals was 24.5% at week 1 and 11.2% at week 4.
The novel MPE-3DP technique produces ECM-based scaffolds with exceptional resolution and fidelity, and hCMPs fabricated with these scaffolds may significantly improve recovery from ischemic myocardial injury. As the Newsweek article notes, Short of a transplant, there isn’t a long-term option to fix a damaged cardiac muscle.
“The concept is to imprint proteins that are native to the body,” says Ogle. “We’ve used stem cell–derived cardiac muscle—cardiac myocytes—and actually mixed those with other cell types needed for blood vessels. This prevents what would otherwise happen naturally: The formation of a different type cells known as fibroblasts, which secrete scar tissue.”
Ogle and her team of 3D printing experts, clinical cardiologists and stem cell engineers have successfully tried the patch on mice. First, the team induced cardiac arrest in the rodents. When they then placed the cell patch on a mouse, researchers saw a significant increase in the functional capacity of the organ after just four weeks. “We generated the continuous electric signal across the patch, and we can pace it: We can increase the frequency of beating up to three hertz, which is similar to a mouse heart,” says Ogle who, this past January, published the findings of their experiment in Circulation Research, a journal from the American Heart Association.
The results of the experiment were so inspiring that in June 2016 the National Institutes of Health awarded her team a grant of more than $3 million, so they can now give pigs heart attacks and fix them with the patch.