Biologic Scaffold

Overview:
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 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. 

Statement of Work:
The proposed work involves the treatment of 15 patients; all of which have suffered from loss of large amounts of functional musculotendinous tissue as a result of trauma. Ten of the patients will be at least 6 months post trauma and five of the patients will have sustained injury within the previous 6 months.  The injury in each of these patients will be such that either heroic tissue transplantation procedures would be required or amputation would be necessary under the current standard of care. These patients will be implanted with a custom designed biologic scaffold composed of SIS-ECM (i.e., the RESTORE™ device, manufactured by DePuy, Inc). The use of this device will be consistent with the labeling approved by the Food and Drug Administration. The measured endpoints will include both structure/morphology (via biopsy) and function (via strength testing and electromyographic measurements) of the remodeled tissue.  A minimum of 6 months follow-up will be collected for each of the 15 patients.  All patients will be treated and follow-up completed within an 18 month period of time.  The surgeries will be conducted by Dr. Steve Wolf at the Institute for Surgical Research (ISR) at Fort Sam Houston, San Antonio, Texas.

Benefit to the war fighter: 
The battle mortality rate for US forces has dropped from 30 percent in WWII to less than 10 percent in Afghanistan and Iraq. The untold, and perhaps more serious, implications of these figures is that our ability to decrease the mortality rate has been accompanied by an increase in the number of seriously injured soldiers who survive but are left with extraordinary injuries; especially complex and severe extremity and head/neck injuries.  Causal factors of this injury profile include changes in tactical warfare, improvements in protective gear (e.g., Kevlar vests), and the recent widespread use of improvised explosive devices (IEDs). Injuries from high-velocity weapons and blast injuries are complex because of their deep penetration and also the burning and blunt trauma involved. Following traumatic soft tissue loss, options for definitive treatment and rehabilitation typically involve a multidisciplinary team effort to provide comprehensive care for affected individuals, including the development of improved prosthetic devices and rehabilitation programs to assist affected individuals with dealing with the psychosocial aspects of lost extremity function.

Impact:
The proposed work involves a regenerative medicine approach for the restoration of functional musculotendinous tissue including the resident blood vessels and nerves. The work has aggressive goals but this proposal supersedes typical approaches that would deliver only incremental improvements in the standard of care.  The proposed approach 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.  Successful completion of our objectives would provide a preferred alternative to present “standard of care” treatment methods and more importantly, offer a realistic possibility of functional tissue replacement.  Importantly, this work will provide early confirmation of the potential for regenerative medicine to restore quality of life to injured war fighters.

Background: 
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, pedical 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.

Researchers: Dr. Steve Badylak, Dr. Neill Turner, John Freund, Dr. Steve Wolf, Dr. Joseph Hsu, Johnny Owens, Vineet Agrawal