HLI researchers create living heart tissue with custom 3-D printer

In the Centre for Heart Lung Innovation (HLI) at St. Paul’s Hospital, Dr. Zachary Laksman and his team have bio-printed living heart tissue using a custom 3D printer built in-house. 

These samples of engineered heart tissue can be used to test new drugs and treatments before reaching the clinical trial stage, providing a more accurate, efficient, and cost-effective alternative to human and/or animal testing. This technology has the potential to transform personalized medicine and is a key step towards eventually being able to print full, functioning organs for transplant. 

Dr. Laksman’s team includes Hattie Luo, PhD candidate in Experimental Medicine at UBC, and Ardin Sacayanan, graduate student in the UBC School of Biomedical Engineering. This accomplishment took three years of development and innovation, enabled by the intersection of engineering and biology.

Custom printer is adaptable, produces consistent results

To create the heart tissues, cells from patient’s blood samples are reprogrammed into stem cells and then differentiated into heart cells. Previously, these cells would be placed by hand in a process called manual casting, until they would self-organize into a tissue structure. This process has limitations, with the resulting samples varying slightly each time.

“We had this vision of using a 3D printer to print heart tissue, so that we could control and pattern complex multicellular heart tissues that replicate the human heart,” says Dr. Laksman. 

Bioprinting the tissue produces results that are more efficient, consistent, and reproducible. However, none of the commercially available 3D bioprinters worked for their purposes, and could not be easily adapted. So, Dr. Laksman and his team decided to build their own.

“We really kind of started from scratch, and so there were a lot of lessons that we had to learn about 3D printing in general,” says Dr. Laksman.

With his bioengineering background, Sacayanan took a lead role in building the printer, manufacturing the design, software, and custom parts the project required. Luo was instrumental in creating the tissues from stem cells, troubleshooting the differentiation process and aiding in quality assurance and cell characterization.

The key to 3-D bioprinting

The key to 3D printing living tissue is ensuring that the cells survive. A careful balance is needed between how much pressure the cells can withstand and the level of control the printing process requires. A bio-ink, a mixture of cells and a substance that provides a supportive environment that allows them to survive the printing process, is needed to strike this balance. This substance dissolves or evaporates when the printing is complete, so that it is not part of the final tissue. 

Dr. Laksman and his team have developed cardiac-specific bio-inks for their printer, but there is room for improvement. Dr. Laksman has received funding from Genome Canada and Genome BC to lead a project with Axolotl Bioscience that will use genomics to create two new cardiac bio-inks that could potentially be commercialized and used to print heart tissue worldwide. 

Clinical trials in a dish

Dr. Laksman’s lab produces samples that are only a few centimeters in size. Many of these can be produced in a short timeframe, and can be used for a process called high-throughput screening, in which multiple drugs are tested at different concentrations simultaneously. This can significantly speed up the process of drug testing.

This technology has great potential for enabling precision medicine, because the samples are genetically identical to the donor the original cells were sourced from. This allows researchers to rapidly test treatments on an individual level and easily evaluate how a treatment differs between diverse demographics. 

Significantly, this presents an alternative to animal testing that is not only faster and cheaper, but more effective. Tests run on these samples of printed human tissue provide substantially more accurate results that those run on animal models. In addition, running a “clinical trial in a dish” can potentially replace some early-stage human trials, saving significant cost, time, and reducing risk to vulnerable patients.

“We can replace early-stage clinical trials to bring safer and more effective drugs to market faster,” says Dr. Laksman. 

He and his team are already using this technology to study multiple conditions, including heart rhythm and heart muscle problems. As part of the next phase of this project, Luo will be developing a disease model for peripartum cardiomyopathy, a serious disease that causes heart failure in pregnancy. Luo will be creating tissue samples that reflect the disease and testing to see the impact of different treatments. 

Increasing complexity to replicate the human heart

There is currently a long way to go before it is possible to 3D print whole, functional hearts – but research is moving in that direction. The heart is not a single pump, but a complex structure made up of many different cell types. Dr. Laksman’s lab has been successful in incorporating multiple cell types in the printed structure. 

“We’re increasing the complexity of the tissues that we print, trying to get to that goal of being able to incorporate not just all the cell types, but all the different structures in the heart,” says Dr. Laksman. This work is a step towards printing patches that could be attached to the heart to fix certain defects.

Currently, the technology is limited by complexity, size and resolution. It is relatively simple for Dr. Laksman’s lab to print small samples, but full organs are not only much bigger, but they also need to have a functioning vascular system to deliver oxygen to the tissue. 

HLI investigator Dr. Yuan Yao, who has a joint appointment between the University of British Columbia Department of Mechanical Engineering and Department of Medicine, has established her own lab adjacent to Dr. Laksman’s, primarily studying vascular bio-fabrication. 

“Theoretically, we will combine both types of tissues together, printing vascularized cardiac tissues,” says Dr. Yao.

Right now, 3D bioprinting does not have the resolution necessary for the level of detail needed to print small blood vessels and capillaries, which are thinner than a human hair. The field is pushing towards achieving that higher resolution, which would enable many different tissues to be printed more accurately.

Dr. Yao was brought on to the HLI in anticipation of an increased focus on bioengineering in the future Clinical Support and Research Centre, Providence Research’s future health innovation hub. Work such as 3D bioprinting will be conducted in its dedicated bioengineering core, which will focus on developing human models, and will have the facilities needed to prototype and fabricate the materials to advance this technology.

One of the most exciting areas of regenerative medicine

This achievement of creating living heart tissue with a custom-built 3D printer is the result of millions of smaller innovations. 3D printing and stem cell technology are coalescing, having developed to a point where they can provide translational solutions that impact people’s lives. Moving forward, Dr. Laksman’s team aims to scale up their production capabilities and increase the complexity of the heart tissue they are able to print.

“The idea of 3D printing tissue is one of the most exciting areas of regenerative medicine in the world right now,” says Dr. Laksman. 

There is significant potential for this technology to change how we treat patients in the future, from expediting drug development, to personalizing medicine, to someday printing whole organs for transplant. This potential is not just limited to the heart - fellow HLI scientist Dr. Emmanual Osei recently developed a 3D bio-printed model that closely resembles the complexity of a human lung, enabling improved testing of respiratory diseases and drug development. 

“There is a lot of creativity, and there are a lot of doors that can be opened with 3D printing,” says Dr. Yao.