Extremity Injury, Muscle Injury, Soft Tissue Injury, Tendon Injury, Traumatic Injury
Conditions
Keywords
MTURR, ECM, Muscle Loss, Tendon, Tendon Repair, Muscle Repair, Soft Tissue Repair, Scaffold, Extracellular Matrix
Brief summary
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 formally evaluated healing and return of function after an extracellular matrix device implantation in 17 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.
Detailed description
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 evaluated healing and return of function after an extracellular matrix device implantation in 17 male and female subjects participating at the University of Pittsburgh under the Department of Plastic Surgery who suffer from injury with loss of skeletal muscle tissue.
Interventions
DEVICEExtracellular Matrix
Extracellular Matrix
Sponsors
United States Department of Defense
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in the Rectified and Integrated EMG Signal of the Tibialis Anterior Muscle At 24 Weeks Post-Operative | approximately 24 weeks post-operative | The physical therapy program was designed to promote activation of the dorsiflexor muscles on the operated side, through manual feedback during volitional contractions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Remodeling Response Approximately 6 Months Post-operative | Approximately 6 months post-operative | The secondary objective is to examine the cellular properties of the biopsy tissue material in each subject for future correlation with clinical outcomes. Seven biopsy samples were collected and stained with Hematoxylin and eosin (H&E) and Masson's trichrome stain. Tissue was stained with antibodies against the progenitor cell markers CD146 and NG2 to show evidence of progenitor cell migration into the remodeling injury site. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Extracellular Matrix Implantation of Extracellular Matrix
Extracellular Matrix: Extracellular Matrix | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 4 |
Baseline characteristics
| Characteristic | Extracellular Matrix |
|---|---|
| Age, Continuous | 35 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Percent Change From Baseline in the Rectified and Integrated EMG Signal of the Tibialis Anterior Muscle At 24 Weeks Post-Operative
The physical therapy program was designed to promote activation of the dorsiflexor muscles on the operated side, through manual feedback during volitional contractions.
Time frame: approximately 24 weeks post-operative
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Extracellular Matrix | Percent Change From Baseline in the Rectified and Integrated EMG Signal of the Tibialis Anterior Muscle At 24 Weeks Post-Operative | 1333 % change |
Secondary
Percentage of Participants With Remodeling Response Approximately 6 Months Post-operative
The secondary objective is to examine the cellular properties of the biopsy tissue material in each subject for future correlation with clinical outcomes. Seven biopsy samples were collected and stained with Hematoxylin and eosin (H&E) and Masson's trichrome stain. Tissue was stained with antibodies against the progenitor cell markers CD146 and NG2 to show evidence of progenitor cell migration into the remodeling injury site.
Time frame: Approximately 6 months post-operative
Population: Demonstrated remodeling response; discrepancy from from those completed in the study (12 of 13) is result of 1 subject not undergoing pathological examination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Extracellular Matrix | Percentage of Participants With Remodeling Response Approximately 6 Months Post-operative | 55 percentage of participants remodeling |