Since the early 2000’s,
McGowan Institute for Regenerative Medicine
faculty have been involved in research that may provide alternatives in the treatment of wounded soldiers. In one early program, McGowan faculty were awarded a share of the federally funded institute—the Armed Forces Institute of Regenerative Medicine (AFIRM)—which is made up of the U.S. Army Institute of Surgical Research (ISR) and a national consortium of institutions led, in part, by the McGowan Institute. In another more recent initiative, the McGowan Institute received funding for several projects through the Office of the Secretary of Defense, MANTECH Program Office, in its Limbs Salvage and Regeneration Program.
Through the AFIRM, the Limbs Salvage and Regeneration research programs, and other complimentary studies, McGowan Institute faculty have identified potentially new therapies that are now under clinical assessment; these studies include:
- Regenerative Medicine Approach to Reconstitute Functional Musculotendinous Tissue
- Burn Scar Contracture
- Helping Wounded Soldiers Recover From Facial Injuries
- Burn Therapy: A Regenerative Medicine Approach
Additional details on the currently available clinical studies related to these technologies, please click
; additional background follows:
Regenerative Medicine Approach to Reconstitute Functional Musculotendinous Tissue
Massive loss of musculotendinous tissue as a result of trauma inevitably leads to serious patient morbidity, surgical challenges for the repair of such injuries, and/or amputation of the affected limb if surgical approaches prove to be untenable. A loss of tissue mass in the gastrocnemius muscle, quadriceps, biceps or triceps, or hamstring muscle group can pose significant surgical challenges. Free muscle grafts, pedicle grafts, and the use of prosthetic materials have all been attempted when primary repair is impossible due to loss of tissue domain; the results of such efforts are typically much less than satisfactory. When autologous grafts are used, donor site morbidity compounds the post surgical problems for the patient and a diminished quality of life follows. Stated differently, existing treatment options for loss of large masses of muscle tissue domain have very limited therapeutic options. A regenerative medicine approach that could reconstitute functional musculotendinous tissue, and by implication include adequate vascularization and innervation, would represent a paradigm shift in the treatment of traumatic tissue injury.
As noted, current treatment options for the loss of large masses of muscle tissue are limited. A regenerative medicine approach that could reconstitute functional muscle-tendon tissue, as well as associated nerves and blood vessels, would represent a paradigm shift in the treatment of traumatic tissue injury. The proposed approach of a study led by McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, professor in the Department of Surgery and director of the Center for Pre-Clinical Tissue Engineering within the Institute, and McGowan Institute for Regenerative Medicine faculty member J. Peter Rubin, MD, chair, Department of Plastic Surgery, director of the Center for Innovation in Restorative Medicine, UPMC endowed professor of plastic surgery, and professor of bioengineering, University of Pittsburgh, involves the use of an "off the shelf" biologic scaffold material that would replace the missing soft tissue, initiate a stem/progenitor cell recruitment process, and facilitate site appropriate functional tissue restoration.
The on-going clinical trial is entitled "Musculotendinous Tissue Unit Repair and Reinforcement (MTURR) with the Use of Biologic Scaffolds for Patients Suffering from Severe Skeletal Muscle Injury." The objective of the study is to assess mechanical strength and function in subjects undergoing Musculotendinous Tissue Unit Repair and Reinforcement (MTURR) with the use of biologic scaffolds for the restoration of both mechanical strength and function in these subjects. This study will formally evaluate healing and return of function after an extracellular matrix device implantation in 40 male and female subjects participating at the University of Pittsburgh under the Department of Plastic and Reconstructive Surgery who suffer from injury with loss of skeletal muscle tissue. Forty other subjects will be treated at 4 or 5 other sites.
The major focus of the Badylak Laboratory is the development of regenerative medicine strategies for tissue and organ replacement. The use of mammalian ECM or its derivatives as an inductive template for constructive remodeling of tissue is a common theme of most research activities. The goal of all projects is clinical translation and improved patient care.
The DoD's Limb Salvage and Regenerative Medicine Initiative and the Muscle Tendon Tissue Unit Repair and Reinforcement (MTURR) Reconstructive Surgery Research study is collaboratively managed by the Office of the Secretary of Defense. The Initiative is focused on rapidly and safely transitioning advanced medical technology in commercially viable capabilities to provide our wounded warriors the safest and most advanced care possible today."
Burn Scar Contracture
Scar formation following injury is a major problem for U.S. soldiers and civilians alike, leading to disabilities in form and function. The annual economic burden of this problem in the United States has been conservatively estimated at more than $4 billion. Burn injuries are particularly prone to extensive and crippling scars. Particularly in the extremities, scars from burn injuries can restrict movement and limit function. Once a tendon or muscle is encased in scar, generally only surgical intervention will offer hope of improvement. Corrective surgery itself, however, can set off a new wound-healing response with associated risks for scarring.
In this project area, J. Peter Rubin, MD, chair, Department of Plastic Surgery, director of the Center for Innovation in Restorative Medicine, UPMC Endowed Professor of Plastic Surgery, and professor of bioengineering, University of Pittsburgh, and his team plan to demonstrate that the use of fibroblasts can be used to treat long standing burn wound contractures in a clinical study. Twenty subjects with a burn scar contracture are being actively enrolled in a Phase I/II trial. The safety cohort part of the trial (4 subjects, abdominal scars) is complete.
As part of the clinical trial, UPMC researchers and surgeons are using an investigational drug designed to improve burn rehabilitation, including the structure, function, and appearance of skin damaged by scarring. The drug is comprised of laboratory grown fibroblasts. Fibroblasts are cells that are responsible for making collagen, a protein that gives skin its strength and elasticity. When injected, the drug may help soften the appearance of the skin and slow the progression of the scar contracture.
The DoD's Limb Salvage and Regenerative Medicine Initiative and the Burn Scar Contracture Study is a second study collaboratively managed by the Office of the Secretary of Defense.
Helping Wounded Soldiers Recover From Facial Injuries
McGowan Institute for Regenerative Medicine faculty member J. Peter Rubin, MD, chair, Department of Plastic Surgery, director of the Center for Innovation in Restorative Medicine, UPMC Endowed Professor of Plastic Surgery, and professor of bioengineering, University of Pittsburgh, continues to receive major funding awards from the DOD to help wounded soldiers recover from devastating facial injuries using innovative surgical technologies based on the biology of fat tissue.
One research program involves the treatment of 20 injured soldiers with facial injuries. "As many as 26% of wounded soldiers suffer facial injuries, and these can have a great impact on quality of life. While we can reconstruct the bony structure fairly well, it is the surrounding soft tissues that give people the recognizable human form. This project investigates how soft tissue grafting can more precisely restore facial form and improve the lives of our wounded soldiers," Dr. Rubin says.
The 1.6 million dollar funding award, known as The Biomedical Translational Initiative, is a program under the Office of the Assistant Secretary of Defense for Health Affairs. The program objective of The Biomedical Translational Initiative is to fund the demonstration and validation of innovative technologies to improve the clinical outcome of wounded military personnel.
"Fat grafting, or moving fat tissue from one part of the body to another, has been used as a cosmetic procedure for decades," comments Dr. Rubin, "but we are now applying this technology for reconstructive surgery to accurately restore facial form after battlefield injuries."
The use of fat grafting for serious facial injuries, such as those resulting from roadside bombs, is facilitated in this project by specially designed devices and instruments for harvesting the fat tissue and implanting it into regions of scarred tissue.
Dr. Rubin assembled a team of specialists for this study with diverse and complimentary expertise. Researchers within the University of Pittsburgh include McGowan Institute faculty member Kacey Marra, PhD, co-director of the Adipose Stem Cell Center; Dr. Gretchen Haas, an expert on measuring the psychological effects of battlefield injuries and how they improve with treatment; and Dr. Barton Branstetter, a radiologist who specializes in high resolution imaging of the face. Other specialists working on this project include Dr. Sydney Coleman, a New York plastic surgeon who pioneered fat grafting surgery, and Colonel Robert Hale, a military surgeon and expert in facial trauma.
Dr. Rubin has maintained a strong focus on the process of moving scientific innovations from the laboratory to the clinic and is excited about the opportunity to bring these treatments to military personnel. "It is really a privilege to be able to apply new advances in surgical science to help wounded soldiers, and we are hopeful that we can make a difference for them."
Burn Therapy: A Regenerative Medicine Approach
Until now burns have usually been treated with skin grafts, which involve taking skin sections from uninjured parts of the patient’s body, or growing sheets of skin artificially, and grafting them over the burn. The grafts can take several weeks or even months to heal, and during the recovery period patients are prone to infections because of the damage to the skin, which is the body’s first line of defense against pathogens
The Bioreactor Group, led by McGowan Institute faculty member Joerg Gerlach, MD, PhD, professor in the Department of Surgery, University of Pittsburgh has identified an alternative approach to mend skin damaged by burns and abrasion-type injuries.
Dr. Gerlach said the new method uses a spraying device that does not injure the cells. In a process taking only an hour and a half in total, a biopsy is taken from the patient’s undamaged skin and then healthy stem cells are isolated from the biopsy and an aqueous solution containing the cells is sprayed on the burn. Results to date suggest that the speed and quality of the healing process are both improved. At the moment the technique has only been used on second-degree burns. Dr. Gerlach’s clinical collaborator is Alain Corcos, MD.
Illustration: Pittsburgh Tissue Engineering Initiative.
Armed Forces Institute of Regenerative Medicine (AFIRM)
The Huffington Post
Bio: Dr. Stephen Badylak
Bio: Dr. J. Peter Rubin
Bio: Dr. Kacey Marra
Bio: Dr. Joerg Gerlach