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Medical team performing surgery in hospital

Bioprinting during surgery could help repair skin and bone

Image credit: Ammentorp/Dreamstime

Researchers in the US have created a method to help repair defects in skin and bone using bioprinting during surgery.

Fixing traumatic injuries to the skin and bones of the face and skull is difficult because of the many layers of different tissues involved. To challenge this, researchers at Penn State University have repaired such defects in a rat model using the technique of bioprinting. They believe their work may lead to faster and better methods of healing skin and bones.

“This work is clinically significant,” said Ibrahim T Ozbolat, an associate professor of engineering science and mechanics, biomedical engineering and neurosurgery at Penn State. “Dealing with composite defects, fixing hard and soft tissues at once, is difficult. And for the craniofacial area, the results have to be aesthetically pleasing.”

In current procedures, fixing a hole in the skull that involves both bone and soft tissue requires using bone from another part of the patient’s body or a cadaver. During this, the bone must be covered by soft tissue with blood flow, also harvested from somewhere else, or the bone will die. Then surgeons would need to repair the soft tissue and skin.

Ozbolat and his team used extrusion bioprinting and droplet bioprinting of mixtures of cells and carrier materials to print both bone and soft tissue. “There is no surgical method for repairing soft and hard tissue at once,” said Ozbolat. “Therefore we aimed to demonstrate a technology where we can reconstruct the whole defect – bone to the epidermis – at once.”

The researchers first tackled bone replacement, beginning in the laboratory and moving to an animal model. They needed a material that was printable and non-toxic and could repair a 5mm hole in the skull. The ‘hard-tissue ink’ was composed of collagen, chitosan, nano-hydroxyapatite, and other compounds and mesenchymal stem cells – multipotent cells found in the bone marrow that create bone, cartilage, and bone marrow fat.

According to the team, the hard-tissue ink extrudes at room temperature but heats to body temperature when applied. This creates a physical cross-linkage of the collagen and other portions of the ink with no chemical changes or the necessity of a cross-linker additive.

Schematic of the skin and bone bioprinting process. After scanning, the bone and then skin layers are bioprinted creating a layered repair with bone, a barrier layer, and dermis and epidermis.

Schematic of the skin and bone bioprinting process. After scanning, the bone and then skin layers are bio-printed, creating a layered repair with bone, a barrier layer, and dermis and epidermis.

Image credit: Ozbolat laboratory, Penn State University

 

The researchers used droplet printing to create the soft tissue with thinner layers than the bone and then used collagen and fibrinogen in alternating layers with crosslinking and growth-enhancing compounds. Each layer of skin including the epidermis and dermis differs, so the bio-printed soft tissue layers differed in composition.

Experiments repairing 6mm holes in the full thickness of skin proved successful. And once the team understood skin and bone separately, they moved on to repairing both during the same surgical procedure. “This approach was an extremely challenging process, and we actually spent a lot of time finding the right material for bone, skin, and the right bioprinting techniques,” said Ozbolat.

After careful imaging to determine the geometry of the defect, the researchers laid down the bone layer. They then deposited a barrier layer mimicking the periosteum, a heavily vascularised tissue layer that surrounds the bone on the skull. “We needed the barrier to ensure that cells from the skin layers didn’t migrate into the bone area and grow there,” Ozbolat explained.

After laying down the barrier, the researchers printed the layers of the dermis and then the epidermis. Ozbolat highlighted it took less than 5 minutes for the bio-printer to lay down the bone layer and soft tissue.

The researchers performed over 50 defect closures and achieved 100 per cent closure of soft tissue in four weeks; they said. The closure rate for bone was 80 per cent in six weeks, but Ozbolat noted that even with harvested bone replacement, bone closure rarely reaches 100 per cent in six weeks.

According to Ozbolat, blood flow to the bone is especially important and inclusion of vascularising compounds is the team’s next step. The researchers also want to translate this research into human applications and are continuing to work with neurosurgeons, craniomaxillofacial surgeons, and plastic surgeons at Penn State Hershey Medical Center, who operates a larger bioprinting device on larger animals.

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