Rensselaer Polytechnic Institute and Yale School of Medicine study: Living skin can now be 3D-printed with blood vessels included

2 Nov

Debra Stang wrote in the Heathline article, Skin Graft, which was Medically reviewed by Catherine Hannan, MD on May 30, 2017:

What is a skin graft?
Skin grafting is a surgical procedure that involves removing skin from one area of the body and moving it, or transplanting it, to a different area of the body. This surgery may be done if a part of your body has lost its protective covering of skin due to burns, injury, or illness.
Skin grafts are performed in a hospital. Most skin grafts are done using general anesthesia, which means you’ll be asleep throughout the procedure and won’t feel any pain.
Why are skin grafts done?
A skin graft is placed over an area of the body where skin has been lost. Common reasons for a skin graft include:
• skin infections
• deep burns
• large, open wounds
• bed sores or other ulcers on the skin that haven’t healed well
• skin cancer surgery
Types of skin grafts
There are two basic types of skin grafts: split-thickness and full-thickness grafts.
Split-thickness grafts
A split-thickness graft involves removing the top layer of the skin — the epidermis — as well as a portion of the deeper layer of the skin, called the dermis. These layers are taken from the donor site, which is the area where the healthy skin is located. Split-thickness skin grafts are usually harvested from the front or outer thigh, abdomen, buttocks, or back.
Split-thickness grafts are used to cover large areas. These grafts tend to be fragile and typically have a shiny or smooth appearance. They may also appear paler than the adjoining skin. Split-thickness grafts don’t grow as readily as ungrafted skin, so children who get them may need additional grafts as they grow older.
Full-thickness grafts
A full-thickness graft involves removing all of the epidermis and dermis from the donor site. These are usually taken from the abdomen, groin, forearm, or area above the clavicle (collarbone). They tend to be smaller pieces of skin, as the donor site from where it’s harvested is usually pulled together and closed in a straight-line incision with stitches or staples.
Full-thickness grafts are generally used for small wounds on highly visible parts of the body, such as the face. Unlike split-thickness grafts, full-thickness grafts blend in well with the skin around them and tend to have a better cosmetic outcome…. https://www.healthline.com/health/skin-graft#types
See, Skin Graft Ruka Shimizu and Kazuo Kishi* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335647/
Tyler Lacoma wrote in What is 3D printing? Here’s everything you need to know:
3D printing is a manufacturing process that creates a three dimensional object by incrementally adding material until the object is complete (this contrasts with subtractive manufacturing techniques such as carving or milling, in which an object is created by selectively removing parts from a piece of raw material). A 3D printer is simply a machine that can take a digital 3D model and turn it into a tangible 3D object via additive manufacturing. While these printers come in many forms, they all have three basic parts….
It’s hard to find a sector that hasn’t been affected by 3D printing. Manufacturing processes around the world have adopted 3D printing techniques to help solve their problems and improve efficiency. When used in mass production, 3D printing tends to be cheaper than any other method. When used to create prototypes, it’s typically the fastest option. But that’s just the beginning! Check just a few of the incredible ways that 3D printing is currently being used.
 Shoes: Companies like Feetz and 3D Shoes manufacture 3D-printed shoes on demand, with plenty of customization options. Bigger brands are getting into the business, too!
 Houses: Yes, we are printing 3D houses now, too! In fact, manufacturer Apis Ctor has developed a house that can be printed and painted in 24 hours.
 Healthcare materials: Common, disposable healthcare objectives, like sample cups, now often come from 3D printing systems. In the prosthetics world, 3D printing is used to create customized prosthetics for individual’s unique bodies and requirements. Advanced systems are even creating 3D skin grafts made out of biological ink.
 Custom ordering: At home or work and feeling left out of the 3D printing business? Thousands of printing companies now offer 3D printing where you specify objects, materials, and place your order online.
 Set Design: Set design and prop-making have fully embraced 3D printing as a far cheaper, faster way to create very specific props for today’s shows and theater. Think how much easier it is to create an alien environment when you can draw, program, and print a usable version of even the most outlandish or historical objects in no time at all! https://www.digitaltrends.com/computing/what-is-3d-printing/

Resources:

Medical Applications of 3D Printing https://www.fda.gov/medical-devices/3d-printing-medical-devices/medical-applications-3d-printing
3D printing in medicine: How the technology is increasingly being used to save lives https://binged.it/2WJ7WsA

3D Printing in Medicine: The Best Applications in 2019                                https://all3dp.com/2/3d-printing-in-medicine-the-best-applications/

Science Daily reported the Rensselaer Polytechnic Institute study: Living skin can now be 3D-printed with blood vessels included

Researchers at Rensselaer Polytechnic Institute have developed a way to 3D print living skin, complete with blood vessels. The advancement, published online today in Tissue Engineering Part A, is a significant step toward creating grafts that are more like the skin our bodies produce 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 this research at Rensselaer. “It provides some accelerated wound healing, but eventually it just falls off; it never really integrates with the host cells.”
A significant barrier to that integration has been the absence of a functioning vascular system in the skin grafts.
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, 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.
In this 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. You can watch Karande explain this development here.
“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,” Karande said. “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 said.
In order to make this usable at a clinical level, researchers need to be able to edit the donor cells using something like the CRISPR technology, so 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 CBIS. “This is a perfect example of how engineers at Rensselaer are solving challenges related to human health….” https://www.sciencedaily.com/releases/2019/11/191101111556.htm

Citation:

Living skin can now be 3D-printed with blood vessels included
Development is significant step toward skin grafts that can be integrated into patient’s skin
Date: November 1, 2019
Source: Rensselaer Polytechnic Institute
Summary:
Researchers have developed a way to 3D print living skin, complete with blood vessels. The advancement is a significant step toward creating grafts that are more like the skin our bodies produce naturally.

Journal Reference:
Tânia Baltazar, Jonathan Merola, Carolina Motter Catarino, Catherine Bingchan Xie, Nancy Kirkiles-Smith, Vivian Lee, Stéphanie Yuki Kolbeck Hotta, Guohao Dai, Xiaowei Xu, Frederico Castelo Ferreira, W Mark Saltzman, Jordan S Pober, Pankaj Karande. 3D bioprinting of a vascularized and perfusable skin graft using human keratinocytes, (..). Tissue Engineering Part A, 2019; DOI: 10.1089/ten.TEA.2019.0201

Here is the press release from Rensselaer Polytechnic Institute:

November 1, 2019
Living Skin Can Now be 3D-Printed With Blood Vessels Included
Development is significant step toward skin grafts that can be integrated into patient’s skin

TROY, N.Y. — Researchers at Rensselaer Polytechnic Institute have developed a way to 3D print living skin, complete with blood vessels. The advancement, published online today in Tissue Engineering Part A, is a significant step toward creating grafts that are more like the skin our bodies produce 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 this research at Rensselaer. “It provides some accelerated wound healing, but eventually it just falls off; it never really integrates with the host cells.”
A significant barrier to that integration has been the absence of a functioning vascular system in the skin grafts.
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, 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.
In this 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.
Watch Karande explain this development:
“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,” Karande said. “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 said.
In order to make this usable at a clinical level, researchers need to be able to edit the donor cells using something like the CRISPR technology, so 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 CBIS. “This is a perfect example of how engineers at Rensselaer are solving challenges related to human health.”
Karande said 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 said. “Wound healing typically takes longer in diabetic patients, and this could also help to accelerate that process.”
At Rensselaer, Karande’s team also includes Carolina Catarino, doctoral student in chemical and biological engineering. The Yale team includes Tania Baltazar, a postdoctoral researcher who previously worked on this project at Rensselaer; Dr. Jordan Pober, a professor of immunobiology; and Mark Saltzman, a professor of biomedical engineering.
This work was supported by a grant from the National Institutes of Health.
CONTACT
Reeve Hamilton
Director of Media Relations and Communications
(518) 833-4277
hamilr5@rpi.edu
For general inquiries: newsmedia@rpi.edu
ABOUT RENSSELAER POLYTECHNIC INSTITUTE
Founded in 1824, Rensselaer Polytechnic Institute is America’s first technological research university. Rensselaer encompasses five schools, 32 research centers, more than 145 academic programs, and a dynamic community made up of more than 7,900 students and more than 100,000 living alumni. Rensselaer faculty and alumni include more than 145 National Academy members, six members of the National Inventors Hall of Fame, six National Medal of Technology winners, five National Medal of Science winners, and a Nobel Prize winner in Physics. With nearly 200 years of experience advancing scientific and technological knowledge, Rensselaer remains focused on addressing global challenges with a spirit of ingenuity and collaboration.

Jeff Kerns wrote in A Look at the Future of Medical 3D Printing, Part 1: Science fiction continues to become reality as 3D printing cuts deeper into the medical industry:

Available Soon
Unveiled at the Radiological Society of North America’s 2017 show, Stratasys unveiled 3D-printed anatomical structures, including disease pathologies that mimic the look and feel of biological parts to accelerate guidance, testing, and education. Engineered in conjunction with top researchers and manufacturers, service initially includes fully functional bone and heart models, with vascular structures expected in early 2018. This technology will eliminate restrictions associated with research on animal, mannequin, or cadaver models—BioMimics effectively mirrors intricacies of both soft tissue and hard bones via multi-material 3D printing.
These are only models, so regulations are fewer than if you were 3D printing the actual organs to go into a patient. While there are recently published reviews describing the use of 3D printing to produce bones, ears, windpipes, jawbones, cells, blood vessels, and more, it will take time before this technology is common practice. An estimate published by the U.S. National Library of Medicine National Institute of Health says that we are less than 20 years from a fully functioning printable heart.
However, it should be cautioned that despite recent significant and exciting medical advances involving 3D printing, notable scientific and regulatory challenges remain, and the most transformative applications for this technology will need time to evolve.
In our next installment, the future of 3D printing tissues, organs, and custom pharmaceuticals will be discussed. Many professionals say 3D printing is getting a lot of hype, but it will be a long time before we start seeing 3D-printed organs. However, the fact that they seem to be saying “It will take a long time,” and not “This will never happen,” is exciting enough. Also, the idea that we may see printed bone and tissue earlier than when organ printing was predicted make it hard not to justify the hype around this technology.
But for the time being, we’ll just need to keep eating right and exercising.
https://www.machinedesign.com/3d-printing/look-future-medical-3d-printing-part-1

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