Musculotendinous Tissue Repair Unit and Reinforcement (MTURR) (MTURR)

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 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.

Study Overview

• Status: Completed
• Conditions: Extremity Injury; Muscle Injury; Soft Tissue Injury; Traumatic Injury; Tendon Injury
• Intervention / Treatment: Device: Extracellular Matrix

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center (WRNMMC)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Extracellular Matrix; Implantation of Extracellular Matrix	Device: Extracellular Matrix; Extracellular Matrix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	approximately 24 weeks post-operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Approximately 6 months post-operative

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: United States Department of Defense

Publications and helpful links

General Publications

• Valentin JE, Badylak JS, McCabe GP, Badylak SF. Extracellular matrix bioscaffolds for orthopaedic applications. A comparative histologic study. J Bone Joint Surg Am. 2006 Dec;88(12):2673-86. doi: 10.2106/JBJS.E.01008.
• Beattie AJ, Gilbert TW, Guyot JP, Yates AJ, Badylak SF. Chemoattraction of progenitor cells by remodeling extracellular matrix scaffolds. Tissue Eng Part A. 2009 May;15(5):1119-25. doi: 10.1089/ten.tea.2008.0162.
• Holcomb JB, Stansbury LG, Champion HR, Wade C, Bellamy RF. Understanding combat casualty care statistics. J Trauma. 2006 Feb;60(2):397-401. doi: 10.1097/01.ta.0000203581.75241.f1.
• Mazurek MT, Ficke JR. The scope of wounds encountered in casualties from the global war on terrorism: from the battlefield to the tertiary treatment facility. J Am Acad Orthop Surg. 2006;14(10 Spec No.):S18-23. doi: 10.5435/00124635-200600001-00005.
• Noe A. Extremity injury in war: a brief history. J Am Acad Orthop Surg. 2006;14(10 Spec No.):S1-6. doi: 10.5435/00124635-200600001-00002.
• Hostetler SG, Schwartz L, Shields BJ, Xiang H, Smith GA. Characteristics of pediatric traumatic amputations treated in hospital emergency departments: United States, 1990-2002. Pediatrics. 2005 Nov;116(5):e667-74. doi: 10.1542/peds.2004-2143.
• Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008 Sep 11;3(3):301-13. doi: 10.1016/j.stem.2008.07.003.
• Reing JE, Zhang L, Myers-Irvin J, Cordero KE, Freytes DO, Heber-Katz E, Bedelbaeva K, McIntosh D, Dewilde A, Braunhut SJ, Badylak SF. Degradation products of extracellular matrix affect cell migration and proliferation. Tissue Eng Part A. 2009 Mar;15(3):605-14. doi: 10.1089/ten.tea.2007.0425.
• Zantop T, Gilbert TW, Yoder MC, Badylak SF. Extracellular matrix scaffolds are repopulated by bone marrow-derived cells in a mouse model of achilles tendon reconstruction. J Orthop Res. 2006 Jun;24(6):1299-309. doi: 10.1002/jor.20071.
• Dziki J, Badylak S, Yabroudi M, Sicari B, Ambrosio F, Stearns K, Turner N, Wyse A, Boninger ML, Brown EHP, Rubin JP. An acellular biologic scaffold treatment for volumetric muscle loss: results of a 13-patient cohort study. NPJ Regen Med. 2016 Jul 21;1:16008. doi: 10.1038/npjregenmed.2016.8. eCollection 2016.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: February 8, 2011
• First Submitted That Met QC Criteria: February 8, 2011
• First Posted (Estimate): February 10, 2011

Study Record Updates

• Last Update Posted (Actual): December 7, 2020
• Last Update Submitted That Met QC Criteria: December 3, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Extracellular Matrix; Scaffold; ECM; Tendon; Muscle Loss; Tendon Repair; MTURR; Muscle Repair; Soft Tissue Repair
• Additional Relevant MeSH Terms: Wounds and Injuries; Soft Tissue Injuries; Tendon Injuries
• Other Study ID Numbers: PRO10010500