3D Tissue Printing: how to fix a broken heart

A few weeks ago scientists around Professor T. Dvir from the Tel Aviv University reported their ground-breaking findings in the field of tissue engineering aided by the advances in 3D tissue printing.

Professor T. Dvir and his interdisciplinary team from the Tel Aviv University are working in the field of cardiac tissue engineering in order to tackle the problem of the high numbers of heart diseases. This research field deals with integrating cardiac cells in 3D biomaterials. These constructs can then be cultured in vitro as a tissue patch. After maturation, the patch can be transplanted onto the defect area of a heart. The 3D biomaterial will degrade over time, leaving only the cardiac cells in place, which contribute to fixing the heart.

One critical factor for this method to be clinically applicable is the biocompatibility of the 3D biomaterial. The tissue patch needs to be similar to the patient’s tissue in its biochemical, mechanical and anatomical properties, in order to be accepted by the body after transplantation.

The current method described by T. Dvir and his team is to reprogram cells back to pluripotent stem cells and then differentiate these into two cell types: cardiomyocytes and endothelial cells. These can be used as material to build a new heart. The cells to be made pluripotent are obtained from the patient’s tissue sample. The cells are separated out of the sample and the remaining extracellular matrix is used to produce a personalised “glue” for building the heart. This so-called hydrogel can be used as scaffold to grow the new heart tissue. The great advantage of this procedure is that it comes directly from the patient’s own tissue and hence is immuno-compatible and specific to the patient.

The actual building material for 3D printing is called bioink. This is produced by combining one differentiated cell type with the hydrogel. This is then used as the ink in the 3D tissue printer.

In their study, the Israeli researchers generated two different bioinks in order to 3D print a small version of a human heart. One bioink, from cardiomyocytes cells, to print the scaffold of the heart tissue and the other, from endothelial cells, to print the blood vessels.

But how did they decide what template to use for 3D printing blood vessels that match the patient? They analysed the patients main blood vessels by computerised tomography and generated a computer-aided design based on this information and mathematical models for oxygen distribution through smaller blood vessels.

The first part of the study proves the concept of using heart patches in mammals. The scientists were able to successfully print a heart patch with blood vessels from rat cells and succeeded in transplanting this patch into hearts of living rats.

Encouraged by this successful proof-of-concept, the researchers used what they had learned and attempted to print a human heart. After further improvement of the procedure, they were able to fabricate “small scale cellularized human hearts with major blood vessels”. The miniature-sized hearts, printed from two bioinks produced from human cells, were 20 mm high and 14 mm in diameter. However, the team around T. Dvir showed the “integrity of the different compartments” and proved that the 3D printed human hearts have clinically relevant anatomical and mechanical properties.

These results are a huge breakthrough in the field of tissue engineering. However, it is still a long way until a fully 3D printed heart can be transplanted into a patient. There is still a lot of research to be done on long-term cultivation of the printed organ in vitro and assembly of organ into the body after transplantation.

However, along the way this study is a big step towards the treatment of defect tissues with 3D printed tissues generated from the patient’s own cells. The first trials on transplanting tissues patches made from reprogrammed cells into rat hearts are very promising for this treatment.

Link to to video explaining the project : https://video.wixstatic.com/video/56c450_da8abb1c876a4f8285e5cb11e376f4ec/480p/mp4/file.mp4

Link to Dvir Lab Website : https://dvirlab.wixsite.com/dvirlab

Link to original publication: https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.201900344