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.
In his article for the New York Times, “Human Muscle, Regrown on Animal Scaffolding,” author Henry Fountain reports on Sergeant Ron Strang, a Marine with a huge divot in his upper thigh where the quadriceps muscle had been. It was a roadside bomb in Afghanistan that blew off part of Sergeant Strang’s left thigh. However, it was Drs. Rubin and Badylak’s use of mammalian extracellular matrix (ECM) in the clinical trial that has enabled Sergeant Strang to grow new muscle, walk easily, run on a treadmill, and think of a post-military career as a police officer.
Dr. Rubin said that early results with Sergeant Strang and a handful of other patients showed that the animal scaffolding was spurring muscle growth. “We are seeing evidence of remodeling of tissues,” he said.
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.
“We’re trying to work with nature rather than fight nature,” said Dr. Badylak.
Also, in clinical trauma research, the U.S. Army’s Institute of Surgical Research (ISR) is examining a variety of combat casualty care problems in trauma patients. ISR is recognized worldwide for its contributions to improved trauma survival. In partnership with the ISR, Dr. Badylak’s ECM technology is used today to help heal soldier lost muscle tissue wounds.
Illustration: McGowan Institute for Regenerative Medicine (Drs. Badylak and Rubin). In the July 9, 2012 image, Marine Sgt. Ron Strang shows his injured leg at the University of Pittsburgh Medical Center in Pittsburgh, Pa. He lost half of his thigh muscle from shrapnel in a bomb blast in Afghanistan, and with an experimental implant of connective tissue developed from pigs, it has had it strengthened. “It’s been a huge improvement,” he says. (AP Photo/Tom Sampson).