A team of doctors and scientists hovers around a patient, a machine, and a computer. The patient has suffered a burn and lies still as his wound is scanned and a 3-D image appears on the computer. After the doctors and scientists observe the wound and analyze the image, a machine whirrs into action. The machine, a 3-D bioprinter, hangs poised above the burn and begins printing skin cells directly into the wound. Although 3-D bioprinters have not yet been approved for use on patients, this scene could soon become reality as the United States Army investigates 3-D bioprinting technologies.
Battlefield Innovation
If necessity is the mother of invention, then battlefield conditions push “necessity” to an entirely new dimension. Battlefield innovation doesn’t just mean smarter body armor or lighter impenetrable vehicles—it also means spectacular leaps in medical innovation. Many of the men and women who enter the battlefield emerge with wounds that would, in earlier conflicts, have been considered fatal. But the outcomes, while not fatal, do result in significant disfigurements and disabilities.
Enter the remarkable U.S. Army program to create a bioprinter which can print 3-D skin onto patients.
Dr. Michael Romanko provides science and technology management support to the Tissue Injury and Regenerative Medicine Project Management Office with the U.S. Army Medical Material Development Activity. He also holds a doctorate in molecular medicine. The doctors and scientists involved in research focus the majority of their energy on skin repair, Romanko said, because blasts from improvised explosive devices (IED) have increased the number of service members suffering from severe burns, lost limbs, and severe facial injuries. The damage to soldier’s skin restricts motion and lowers their quality of life.
“There was an increasing need to deliver therapies for wounded warriors. We saw a spike in the severity of the trauma that these soldiers were receiving. As we increased the quality of battle armor, the injuries they were surviving were that much more debilitating, ” Romanko said.
Armed Forces Institute of Regenerative Medicine
To better treat wounded service members, the Department of Defense established the Armed Forces Institute of Regenerative Medicine (AFIRM) in 2008. AFIRM aims to promote integration of development, from laboratory research to clinical trials, as the best means of bringing regenerative medicine therapies to practice. AFIRM consists of an interdisciplinary network of universities, military laboratories, and investigators, all working under a cooperative agreement. A new agreement was made in 2013 after reviewing the initial success of the first five years. Currently, about 30 universities, hospitals, and additional partners, led by the Wake Forest Institute for Regenerative Medicine, make up the coalition of AFIRM research facilities.
Even as AFIRM expands its regenerative work in a wide variety of areas, skin repair remains one of the most important and still unsolved problems for wounded soldiers. And 3-D printing is creating some amazing possibilities. Currently, the AFIRM scientists are testing 3-D bioprinting on skin, genitourinary, and facial injuries.
The Need Is More Than Skin Deep
Skin injuries are of vital concern to U.S. Army doctors because, in this new era of IEDs and other incendiary devices, burns account for 10% to 30% of battlefield injuries.
“Everyone has a different type of injury, and not everyone’s skin injury looks the same, ” said Romanko. Skin bioprinting would provide a scalable form of personalized medicine.”
Although 3-D bioprinting has yet to be used on any patients, scientists know how translating the technology from the laboratory to the clinic would work. A team of doctors and scientists would complete a scan of the patient’s burn and build a 3-D map of the injury. This computerized 3-D map would tell the bioprinter where to deposit layers of skin cells.
How Does It Work?
The bioprinter works like an inkjet printer. Healthy skin cells are loaded into a cartridge, similar to an ink cartridge, and placed in the printer. Just like the different colors of ink, there are two distinct types of skin cells, fibroblasts and keratinocytes. The computer tells the bioprinter where to start printing and what types of cells need to be used for the depth of injury or layer of skin being printed. Fibroblasts make up the deep layer of skin while keratinocytes are used in the top layer. After the printer lays down the skin cells, they will grow to become new layers of skin and heal the wound. A patch of skin one-tenth the size of the burn is enough to grow the skin cells necessary for skin printing.
Scientists who are developing these techniques expect that the ability to actually print skin cells into open wounds is not only viable, but a practical solution to a very complex and enduring trauma problem.
“The scars that soldiers develop as a result of burns constrict movement and disfigure them permanently. The initiative to restore high-quality skin that is elastic and complete with sweat glands, appropriate pigmentation and hair follicles is incredibly important, ” Romanko said.
Other Uses
In addition to using 3-D bioprinters to reconstruct skin wounds, AFIRM has also begun projects aiming to use 3-D bioprinting technology to generate organs, limbs, and vascular systems. Other projects within AFIRM focus on creating complex tissue components with bone and muscle. Scientists at the Wake Forest Institute for Regenerative Medicine have been able to print a kidney, an ear, and bones in the finger.
“In the future, through additive manufacturing, we may be able to produce a heart and do transplants, ” said Dr. Thomas Russell, director of the U.S. Army Research Laboratory. “Many of the injuries soldiers receive in the field are not traditional. A lot of the medical community sees this as a new approach to medicine.”
Although using 3-D bioprinting for skin repair has been well researched, printing other organs and systems is still in the early stages. AFIRM has completed several studies investigating the use of bioprinters, one of which is entitled “3-D Printed Biomaterials for Maxillofacial Tissue Engineering and Reconstruction – A Review.” Authored by XingGuo Cheng, Ph.D., from Southwest Research Institute; James J. Yoo, Ph.D., Hyun-Wook Kang, Ph.D., and Sang Jin Lee, Ph.D. from the Wake Forest Institute for Regenerative Medicine; and Colonel Robert G. Hale, D.C. and Lt. Colonel (USAF) Michael R. Davis, M.D. FACS from the U.S. Army Institute of Surgical Research, this study covers new innovations in 3-D printing and the use of bioprinting for the reconstruction of maxillofacial tissues.
Creating Bone
The authors found that 3-D bioprinters can be used to create scaffolds for bone regeneration or a bone substitute implant in maxillofacial surgery. These scaffolds can be made to the shape of the patient’s facial structures and with internal pore connectivity. The 3-D printer was utilized to create precise dental prosthetics for patients with oral injuries in addition to printing a PCL facemask, which the bioprinters then used as a base to deposit a collagen-based wound matrix.
The further development of 3-D printing technologies for use in maxillofacial tissue engineering is critical in treating injured servicemen and women. With an increase in improvised explosive devices used in war, soldiers are experiencing unique craniomaxillofacial (CMF) injuries. CMF injuries make up as many as 42% of all injuries suffered by Department of Defense service members. Of the CMF wounds, 44% of injuries are bony fractures. AFIRM continues to develop 3-D bioprinting technologies to better the lives of wounded warriors, although further laboratory research is required along with the completion of several federal regulatory steps before the start of clinical trials.
Who Pays?
In order to develop complex technologies, like the 3-D bioprinter, the United States Army had to pull together funds from a variety of sources and experts from across academic and medical fields. The multidisciplinary team includes engineers and bioimaging experts in advanced printing and scanning technologies, biologists and physicians—all working to create the previously unimaginable—a system to scan an injury site, create a 3-D image of the void, design exactly the right cell based 3-D matrix and print that specific cell tissue implant directly into the wound!
The U.S. Army, the Office of Naval Research, the Air Force Surgeon General’s Office, the Veterans Health Administration, the National Institutes of Health, and the Office of Assistant Secretary of Defense for Health Affairs all provided funding to AFIRM. Other organizations associated with AFIRM receive funding from other federal, state, and private sources.
Although AFIRM is currently developing the 3-D bioprinter technology to better the lives of servicemen and women wounded in war, expanding the technology will help treat injured soldiers and civilians alike and ensure the long-term viability of 3-D bioprinting.
“This has a very widespread use, not only to the military audience, but also to the civilian population, ” Romanko said. “We need a larger commercialization audience in order to be a self-sustaining technology.”
No kidding.
very important these innovations