The future of wound healing

One of the technologies to come out of a research project funded by Armed Forces Institute of Regenerative Medicine (AFIRM) to apply regenerative medicine to battlefield injuries is a 3D printer that prints, or applies, skin cells onto burn wounds. The way it works is a scanner determines the wound’s terrain, including size and depth, providing a blueprint of how the printer will fill the full-thickness wound. The printer, armed with two types of skin cells taken from a small biopsy would then be applied and cover the wound.

The big benefit of the technology is that clinicians caring for burn wounds would only need a biopsy of uninjured skin one-tenth the size of the burn to grow the skin cells needed to fill the wound with skin printing.

A close -up view of the experimental bio-printer nozzle created by Wake Forest Institute for Regenerative Medicine scientists that deposits cells on a burn wound. Photo: WFIRMThe technology showed promising results in animal studies but needs funding for future development in humans, according to John Jackson, Ph.D., associate professor at the Institute for Regenerative Medicine at Wake Forest University School of Medicine. Dr. Jackson is a focus leader of the genitourinary focus area for AFIRM 2, the next phase of the research. While many institutions are involved in AFIRM 2, Wake Forest was the administrative lead for AFIRM 1, as one of two consortia, and is the administrative lead for AFIRM 2, according to Dr. Jackson.

NEXT: See how it works

Skin bio-printing: the concept

Wake Forest researchers developed a clinical prototype of the skin bio-printer and tested it in several animal studies. Today’s prototype is mobile, and would allow clinicians to wheel it to a patient’s hospital bed and print directly on the wound. 

Initial animal studies for skin bio-printing were in nude mice, before researchers moved to an incisional wound model in pigs.

In the pig study, scientists made incisional wounds on the pigs’ backs. Each was 10 cm by 10 cm, or 100 cm². They left one of the wounds untreated, using standard care of bandaging. In the second wound, they used a matrix, or hydrogel, which included fibrin and collagen. In the third wound, they used that same hydrogel with the culture expanded cells and applied two different layers of cells.

“We would add the dermal fibroblasts to the fibrin collagen hydrogel and print that first; then, we would print the keratinocytes in the hydrogel over top of that first layer,” he says.

By “printing,” Dr. Jackson means applying air pressure, which pushes the hydrogel and cells out of the print nozzle.

The skin cells came from a small biopsy of an uninjured area on the pig. They isolated two cell types -keratinocytes, then, dermal fibroblasts - then, expanded the cell types in culture to later bio print them directly into the created wounds.

“For our technique, we actually take small biopsies of skin and expand them in culture, so you have to do that expansion in a special facility under very strict conditions because you’re manipulating the cells,” Dr. Jackson says. “Then we take the cells and place them into our bio printer. In conjunction with the skin bio printer, we have a laser scanner. We scan the wound, which gives a 3D rendering of the wound. That information is processed by the computer and controls the bio printer to fill the wound.”

The scanner determines the number of cells needed for the deeper and shallower wound areas, he says.

The researchers found that the bio-printed cells enhanced the healing of the wound by three to four weeks, when compared to untreated or the matrix treated wounds. A manuscript is under review describing the data from these studies, Dr. Jackson says.

NEXT: Where does the technology stand?

Where does the technology stand now?

Research funding for 3D printing of skin cells onto burn wounds ended with the pig studies and AFIRM 1. It’s not because the technology didn’t work. It did, Dr. Jackson says. But the reviewers had to pick and choose which projects would get further funding, according to Dr. Jackson.

A WFIRM scientist prepares to scan a burn wound on a fake arm to demonstrate how the bio-printer works to deposit cells on a wound to enhance healing. Photo credit: WFIRMThe Department of Defense, National Institutes of Health and Armed Forces Regenerative Medicine Institute have since earmarked $75 million for AFIRM 2, which is beginning the fourth of five years. The research in AFIRM 2 is looking at restoring function to traumatized limbs, reconstructing facial and skull injuries with tissue regeneration; treatments to prevent rejection of face, hand and other transplants; genital and urinary organ and lower abdomen reconstruction; as well as skin regeneration for burn injuries.

Wound healing studies continue in AFIRM 2, but in different areas. For example, Wake Forest researchers are looking at whether an amniotic membrane preparation is effective at healing wounds. The research funding for AFIRM 2 was for five years. There are two years left, according to Dr. Jackson.

As for skin bio-printing with the 3D printer, Dr. Jackson says his colleagues at Wake Forest are compiling the animal data in order to submit an application for an investigational new drug (IND), for a clinical trial.

“The application to the FDA is very complicated. We’re using two cells types, so that would go in as a biologic to the FDA. Then, we’re using a skin bio printer that is sitting over a patient and applying the cells to the patient. So that is classified as a device. We have to get all of that approved to proceed to a clinical trial,” he says.

The result is that skin bio-printing with this device will not be commercially available anytime soon, but it’s on the horizon, Dr. Jackson says.

Disclosure: Dr. Jackson reports no relevant disclosures, other than he is leading the area of research for AFIRM 2.