Scientists in the US have created 3D-printed skin complete with blood vessels, an advancement which they hope could be a significant step toward creating grafts that are more like the skin our bodies naturally produce.
The team of researchers at Rensselaer Polytechnic Institute in New York and Yale School of Medicine combined cells found in human blood vessels with other ingredients, including animal collagen, and printed a skin-like material.
After a few weeks, the cells started to form into vasculature (the arrangement of blood vessels in an organ or part), after which the skin was transplanted onto a mouse. Following this procedure, the team found the skin connected with the animal’s vessels.
“Right now, whatever is available as a clinical product is more like a fancy Band-Aid,” said Pankaj Karande, an associate professor of chemical and biological engineering and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer.
“It provides some accelerated wound healing, but eventually it just falls off. It never really integrates with the host cells,” he added.
A significant barrier to the integration between cells has been the absence of a functioning vascular system in the skin grafts. For several years, Karande and his team have been working to tackle this challenge.
In one of the team’s first papers on the subject, the researchers found they could take two types of living human cells, make them into ‘bio-inks’ and print them into a skin-like structure.
Since then, he and his team have been working with researchers from Yale School of Medicine to incorporate vasculature to these cells.
In their latest study, the researchers demonstrated that if they add key elements – including human endothelial cells, which line the inside of blood vessels, and human pericyte cells, which wrap around the endothelial cells – with animal collagen and other structural cells typically found in a skin graft, the cells start communicating and forming a biologically relevant vascular structure within the span of a few weeks.
Karande explains this development in the video below.
Karande said: “As engineers working to recreate biology, we’ve always appreciated and been aware of the fact that biology is far more complex than the simple systems we make in the lab.
“We were pleasantly surprised to find that, once we start approaching that complexity, biology takes over and starts getting closer and closer to what exists in nature.”
Once the Yale team grafted it onto a special type of mouse, the vessels from the skin printed by the Rensselaer team began to communicate and connect with the mouse’s own vessels.
“That’s extremely important because we know there is actually a transfer of blood and nutrients to the graft which is keeping the graft alive,” Karande added.
In order to make this process usable at a clinical level, however, the researchers would need to be able to edit the donor cells using CRISPR (gene editing) technology to ensure that the vessels can integrate and be accepted by the patient’s body.
“We are still not at that step, but we are one step closer,” Karande said.
“This significant development highlights the vast potential of 3D bioprinting in precision medicine, where solutions can be tailored to specific situations and eventually to individuals,” said Deepak Vashishth, the director of CBIS. “This is a perfect example of how engineers at Rensselaer are solving challenges related to human health.”
Karande added that more work will need to be done to address the challenges associated with burn patients, which include the loss of nerve and vascular endings.
However, the grafts his team have created bring researchers closer to helping people with more discrete issues such as diabetic or pressure ulcers.
“For those patients, these would be perfect, because ulcers usually appear at distinct locations on the body and can be addressed with smaller pieces of skin,” Karande explained. “Wound healing typically takes longer in diabetic patients and this could also help to accelerate that process.”
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