3D bioprinted cell patches used to repair damaged diaphragms in groundbreaking study

The article was originally published on 3ders.org

Researchers in Japan have used a 3D bioprinted cellular patch to repair damaged human diaphragms attached to rats, seeing “complete tissue integration” of the printed grafts after a period of time. The exciting bioprinting research paves the way for a clinical trial.


Research add the bioprinted patch of human cells to a damaged diaphragm


While scientific experiments on rats can be a little hard to stomach, research in the field of 3D bioprinting is highly dependent on the practice. Over the last few years, we’ve seen bioprinting experts—particularly those in Japan—make huge strides in their research by implanting 3D printed liver buds, and later 3D printed tracheas, into live rats.

When these experiments go to plan, they represent hugely important steps on the road to transplantable bioprinted human organs—the end goal for many bioprinting researchers and companies.

Two of the researchers responsible for those 3D printed liver buds, Koichi Nakayama (Saga University, co-founder and shareholder of Cyfuse Biomedical) and Tomoaki Taguchi (Kyushu University), have now returned with a new research paper, put together with other researchers from Kyushu and Saga.

This new research attempts the 3D bioprinting and regeneration of a different body part: diaphragms.

The bioprinting research has been carried out because of an urgent need within paediatric surgery to find ways to heal diaphragmatic hernias with the use of native tissue (tissue taken from other parts of a patient’s body).

The current use of so-called “mesh” patches in medicine, which can consist of organic and inorganic materials, often results in a recurrence of the hernia, something doctors and patients want to avoid at all costs. Many of these meshes are also unable to function over a period of time, since they do not grow as a patient grows.

By using a 3D bioprinter to generate large scaffold-free tissue patches composed of human cells (human dermal fibroblasts and human umbilical vein endothelial cells), the researchers attempted to repair damaged human diaphragms attached to rats.


Cyfuse Biomedical's Regenova 3D bioprinter was used for the study


They hoped that successful research could lead to improved treatments for those born with congenital diaphragmatic hernia, for which there is no viable therapy besides the mesh patch.

For the exciting research, the scientists’ chosen bioprinter was Cyfuse Biomedical’s Regenova 3D bioprinter, which uses a unique cell-skewering process known as the Kenzan Method. Their printed cellular patches had an approximate length of 20 mm, inner diameter of 3 mm, and tube wall thickness of 1 mm.

As is to be expected with an established bioprinter like the Regenova, the 3D printed cellular patches were strong and highly elastic, making them suitable for the transplantation.

In what could be highly promising news for those in healthcare, the procedure was a big success. The rats survived for 710 days after having the bioprinted patches attached, and the researchers noted “complete tissue integration of the grafts during rat growth.”

Histology showed regeneration of muscle structure, neovascularization, and neuronal networks within the reconstructed diaphragms. Because of this, the Japanese researchers say their results “demonstrate that created cellular patches are a highly safe and effective therapeutic strategy for repairing diaphragmatic defects, and thus pave the way for a clinical trial.”

“To our knowledge,” the researchers say, “this is the first report of diaphragmatic defect repair using created grafts composed only of cells.”

The future? The researchers now plan to attempt a similar bioprinting feat on a larger animal, such as a rabbit, using a new Kenzan design to create larger cellular patches measuring 5 × 6 cm.

The research, “Regeneration of diaphragm with bio-3D cellular patch,” has been published in the journal Biomaterials.