Musculotendinous Tissue Unit Repair and Reinforcement (MTURR) Coordinating Center

Loss of musculotendinous tissue as a result of trauma inevitably leads to severe morbidity
for the subject and surgical challenges for the caregiver. The reconstruction of tissue
following such injuries is often not possible and surgical options are extremely limited.
Amputation of the affected limb is not an uncommon outcome. Free muscle grafts, pedicle
grafts, and the use of prosthetic materials have all been attempted when primary repair is
not possible due to loss of tissue domain. The results of such efforts are typically
disheartening. If autologous grafts are used, donor site morbidity compounds the post
surgical problems with resultant diminished quality of life. Stated differently, the
existing treatment options for treatment of the loss of large amounts of skeletal muscle
tissue with scarring are extremely limited because the existing tendon structures are
damaged and lack strength. A Repair and Reinforcement approach with a biocompatible device
would represent a paradigm shift in the treatment of traumatic tissue injury. This approach
involves releasing scar tissue that constricts movement of the existing tendon, repairing
damaged tendon and musculotendinous units with suture repair, and reinforcing the repair
with a biologic scaffold material. The biologic scaffold is composed of animal derived
collagen and the approved by the FDA as devices for reinforcement of soft tissues repaired
by sutures or suture anchors, during tendon repair surgery." Additionally, as listed in the
FDA 510k approval, these devices" provide a remodelable scaffold that is replaced by the
subject's own soft tissues." These biologic materials fall into a category of implantable
devices known as extracellular matrix (ECM) because they are composed of proteins that
surround the cellular elements in mammals. No living cells are found in these ECM
implantable devices. ECM devices are made by many commercial manufacturers and have been
used for a variety of reconstructive surgical procedures for years. Because the ECM implant
becomes populated with subject cells and blood vessels, the repair may be stronger and the
new tissue growing within the device could possibly contribute to improved function by
augmenting the tendon structure and allowing ingrowth of adjacent muscle fibers. 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 4-5 military
sties who suffer from injury with loss of skeletal muscle tissue. The University of
Pittsburgh under the Department of Plastic Surgery is the Coordinating Center for this
multi-site study.

Inclusion Criteria:

- Patients with the following characteristics will be eligible to participate in the
study:

- Age: 18 to 70 years of age and able to provide informed consent

- Civilian, and current or former military personnel are eligible to participate

- Have suffered injury resulting in a structural deficit of a minimum of 20% of
the muscle group mass and a functional deficit of a minimum of 25% when compared
to the contralateral limb; or if bilateral injury is present to extremities, the
potential surgical extremity is to be compared against normal expected values of
a sample population of similar age and gender, and evidence of remaining tendon
and musculotendinous units that could be surgically repaired with sutures.

- Injuries may encompass a single muscle belly or compartment. Whether an area is
expected to be repaired by sutures will be determined from imaging studies and
physical examination.

- Have suffered traumatic injury within the last 18 months to the upper and/or
lower extremity; Target of 18 months or less but subject's may be enrolled with
injury outside this range if the principal investigator determines that there is
viable muscle in the injured compartment determined by clinical exam and imaging
studies.

- Eligible for study procedures 3 months post injury with stability determined by
the Principal Investigator and/ or MD Co-Investigator

- Willing and able to comply with follow up examinations, radiographic studies,
physical therapy, muscle biopsy and laboratory tests.

Exclusion Criteria:

- Patients with the following characteristics will be excluded from participating in
the study:

- Inability to provide informed consent

- Poor nutrition (demonstrated by abnormal lab range for serum Albumin and
Pre-Albumin values)

- Chronic disease such as congestive heart failure, liver disease, renal disease,
or diabetes

- Active and unstable disease state or infection anywhere in the body per MD's
evaluation and determination (demonstrated by stated or medical record history
and abnormal lab range for CBC with Differential and Platelet, and chemistry
panel values)

- Known coagulopathy (demonstrated by stated or medical record history of
diagnosis)

- Pregnancy (demonstrated by a positive result of a urine pregnancy test)

- Diagnosis of cancer within last 12 months and /or actively receiving
chemotherapy or radiation treatment

- Axis I diagnosis DSM-IV (e.g., Schizophrenia, Bipolar Disorder). Subjects who
are found to be stable on medication and receive psychiatric clearance could be
eligible for study participation per the Physician's discretion

- Subjects with complete muscle/tendon gaps greater than 5 cm that are obvious on
imaging studies and are unlikely to be reasonably repaired with sutures and
reinforcement, and will be excluded.