AMS Spring 2023

3D Printing Technology and Engineering Used to Regenerate Heart Muscle Tissue

6K SmarTech

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In the past, the University of Saskatchewan (U of S) has used 3D printing technology to help with brain surgery, but now researchers from the Canadian university are focusing on matters of the heart. Mohammad Izadifar, a multi-discipline researcher who works with biomedical and chemical engineering, is combining engineering, 3D printing, and medicine to repair damaged hearts by regenerating heart muscle tissue.

Izadifar is certified in open heart surgery on rats at the university’s College of Medicine, and so is conducting his research there, as well as out of the College of Engineering; he’s also using the biomedical imaging and therapy (BMIT) beamline at Canadian Light Source (CLS), a synchrotron light source facility located on the U of S campus.

Izadifar explained, “The problem is the heart cannot repair itself once it is damaged due to a heart attack.”

He has proved that his 3D printed human cells, or heart patch, will be able to, in theory, start growing as they are supposed to, and outlined his innovative work in a research paper, titled “Bioprinting Pattern-Dependent Electrical/Mechanical Behavior of Cardiac Alginate Implants: Characterization and Ex Vivo Phase-Contrast Microtomography Assessment,” that was published this month in the Tissue Engineering journal; in addition to Izadifar, co-authors include Paul Babyn, Michael E. Kelly, Dean Chapman, and Xiongbiao Chen.

The abstract explains, “Three-dimensional (3D)-bioprinting techniques may be used to modulate electrical/mechanical properties and porosity of hydrogel constructs for fabrication of suitable cardiac implants. Notably, characterization of these properties after implantation remains a challenge, raising the need for the development of novel quantitative imaging techniques for monitoring hydrogel implant behavior in situ. This study aims at (i) assessing the influence of hydrogel bioprinting patterns on electrical/mechanical behavior of cardiac implants based on a 3D-printing technique and (ii) investigating the potential of synchrotron X-ray phase-contrast imaging computed tomography (PCI-CT) for estimating elastic modulus/impedance/porosity and microstructural features of 3D-printed cardiac implants in situ via an ex vivo study. Alginate laden with human coronary artery endothelial cells was bioprinted layer by layer, forming cardiac constructs with varying architectures. The elastic modulus, impedance, porosity, and other structural features, along with the cell viability and degradation of printed implants were examined in vitro over 25 days. Two selected cardiac constructs were surgically implanted onto the myocardium of rats and 10 days later, the rat hearts with implants were imaged ex vivo by means of PCI-CT at varying X-ray energies and CT-scan times. The elastic modulus/impedance, porosity, and structural features of the implant were inferred from the PCI-CT images by using statistical models and compared with measured values. The printing patterns had significant effects on implant porosity, elastic modulus, and impedance. A particular 3D-printing pattern with an interstrand distance of 900 μm and strand alignment angle of 0/45/90/135° provided relatively higher stiffness and electrical conductivity with a suitable porosity, maintaining high cell viability over 7 days. The X-ray photon energy of 30–33 keV utilizing a CT-scan time of 1–1.2 h resulted in a low-dose PCI-CT, which provided a good visibility of the low-X-ray absorbent alginate implants. After 10 days postimplantation, the PCI-CT provided a reasonably accurate estimation of implant strand thickness and alignment, pore size and interconnectivity, porosity, elastic modulus, and impedance, which were consistent with our measurements.”

Mohammad Izadifar [Image: University of Saskatchewan]

One of the most important factors of the project, according to Izadifar, is finding the correct gel medium to use as bioink for 3D printing live human tissue. He used a natural, algae-based hydrogel that’s biocompatible and won’t be rejected by the human body; the hydrogel is also biodegradable.

Izadifar said, “My goal is to take stem cells from the patient and then, in-vitro, I expand and instruct them to become heart cells.”

Once the 3D printed patch starts to get absorbed by the heart, these cells then grow into dense heart muscle, and if all goes as planned, the lab rat’s heart, and eventually human hearts, will start shooting new blood vessels into the patch so that the new tissue has a good oxygen supply and won’t fail. The goal is to have the cells tightly align in the heart patch so they can conduct electricity the same way that natural heart muscle is able to.

Heart with 3D printed patch. [Image: Mohammad Izadifar]

However, his 3D printed heart patch is invisible to conventional medical imaging techniques once it’s been implanted in the rats, meaning that Izadifar would be unable to check on its progress. So he worked with the CLS to create a new X-ray imaging technique that can monitor the patch after implantation. In some of the CLS images submitted to the journal, you can see the 3D printed heart patch, and human cells that have been arranged in strands that are 200 microns wide, with the distance between each one measuring about 400 microns.

“If it is to become heart tissue, the patch needs to be robust and conductive,” Izadifar explained. “With different 3D printing patterns, we can control the toughness, conductivity and cell alignment of the patch. With the medical imaging technique that I developed at the CLS, we would be able to monitor the 3D-printed heart patch during the healing process.”

Chapman, the science director of the CLS, says that it’s been great working with an enthusiastic researcher like Izadifar “at a facility well suited to the new field of tissue engineering using 3D printing.”

Chapman explained, “Our biomedical beamline (BMIT) is in a very unique environment on a university campus with a college of medicine and a veterinary college where animal models of research must be used.”

The BMIT is unique because it slightly refracts high intensity X-ray beams in a phenomenon radiologists refer to as phase contrast imaging – images of the material at the molecular level can be shown at 1,000 times bigger than a direct look when the light is refracted. This allows researchers to watch the 3D printed tissue turn into heart muscle.

Chapman said, “Phase contrast imaging as we do on this beamline is the future of radiology.”

3D printed patches are proving an area of increasing interest for researchers as the technology could lead to healthier heart repair.

[Sources: University of Saskatchewan, Canadian Light Source]

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