Printing vascularized skin

Researchers have developed a way to 3D print vascularized, living skin

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TROY, N.Y.—November brought word that researchers at Rensselaer Polytechnic Institute have developed a way to 3D print living skin, complete with blood vessels. The study, published online in Tissue Engineering Part A, is a significant advancement toward creating grafts more like the skin the body produces naturally.
“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), who led the research at Rensselaer. “It provides some accelerated wound healing, but eventually it just falls off; it never really integrates with the host cells.”
The absence of a functioning vascular system in the skin grafts is a significant barrier to that integration.
Karande has been working on this challenge for several years, previously publishing one of the first papers showing that researchers could take two types of living human cells, turn 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.
In this latest paper, the researchers show 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.
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.
“Right now, there are grafts that are used in the clinic that are available commercially, but one of the challenges is that when you put on the graft, it eventually sloughs off,” noted Karande in a video. “The blood vessels are important because they are the ones that feed the graft from the host. The bring the nutrients, they also help to remove the metabolites. So if you don’t have these communication channels, between the host and the graft, the graft is not going to survive.”
“Now, we’re combining these [grafts] with more types of cells—with melanocytes, with endothelial cells, with pericytes—and what we see is that we have this really nice functional vasculature that forms in the lab, when we print the tissue. Then when we graft them on animal wounds, we see that the graft integrates nicely with the animal skin,” Karande continued. “But what was really exciting for us was to see that we have connections between the mouse blood vessels—in this case, the host—and with the blood vessels that we had printed in the graft. And that’s exactly what we want. That’s what’s going to make the graft integrate.”
“We’ve always appreciated, as tissue engineers, as engineers working to recreate biology, the fact that biology is far more complex than the simple systems we make in the lab. But these new platforms, new technologies, like ... 3D bioprinting, what they are allowing us to do is really start doing that organization, that engineering … at the length scale of proteins, at the length scale of cells, positioning the cells exactly where they would appear in the natural context,” he added in the video.
In order to make this graft technology usable at a clinical level, researchers need to be able to edit the donor cells using something like CRISPR technology, so 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 pointed out.
He acknowledged 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. But the grafts his team has created bring researchers closer to helping people with more discrete issues, like 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 stated. “Wound healing typically takes longer in diabetic patients, and this could also help to accelerate that process.”
“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,” concluded Deepak Vashishth, the director of CBIS. “This is a perfect example of how engineers at Rensselaer are solving challenges related to human health.”

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