A murine model of volumetric muscle loss and a regenerative medicine approach for tissue replacement.

Volumetric muscle loss (VML) resulting from traumatic accidents, tumor ablation, or degenerative disease is associated with limited treatment options and high morbidity. The lack of a reliable and reproducible animal model of VML has hindered the development of effective therapeutic strategies. The present study describes a critical-sized excisional defect within the mouse quadriceps muscle that results in an irrecoverable volumetric defect. This model of VML was used to evaluate the efficacy of a surgically placed inductive biologic scaffold material composed of porcine small intestinal submucosa-extracellular matrix (SIS-ECM). The targeted placement of an SIS-ECM scaffold within the defect was associated with constructive tissue remodeling including the formation of site-appropriate skeletal muscle tissue. The present study provides a reproducible animal model with which to study VML and shows the therapeutic potential of a bioscaffold-based regenerative medicine approach to VML.

[1]  A. Mauro SATELLITE CELL OF SKELETAL MUSCLE FIBERS , 1961, The Journal of biophysical and biochemical cytology.

[2]  H. Price,et al.  ULTRASTRUCTURAL ALTERATIONS IN SKELETAL MUSCLE FIBERS INJURED BY COLD. II. CELLS ON THE SARCOLEMMAL TUBE: OBSERVATIONS ON "DISCONTINUOUS" REGENERATION AND MYOFIBRIL FORMATION. , 1964, Laboratory investigation; a journal of technical methods and pathology.

[3]  D. Allbrook,et al.  The structure of the satellite cells in skeletal muscle. , 1965, Journal of anatomy.

[4]  A. d'Albis,et al.  Regeneration of muscles after cardiotoxin injury I. Cytological aspects , 1988, Biology of the cell.

[5]  T. Paternostro-Sluga,et al.  Donor‐Site Morbidity of the Gracilis Flap , 1995, Plastic and reconstructive surgery.

[6]  R. Armstrong,et al.  Muscle function and protein metabolism after initiation of eccentric contraction-induced injury. , 1995, Journal of applied physiology.

[7]  J. Heino,et al.  Satellite cell proliferation and the expression of myogenin and desmin in regenerating skeletal muscle: evidence for two different populations of satellite cells. , 1995, Laboratory investigation; a journal of technical methods and pathology.

[8]  S. Badylak,et al.  Intestine submucosa and polypropylene mesh for abdominal wall repair in dogs. , 1996, The Journal of surgical research.

[9]  G Cossu,et al.  Muscle regeneration by bone marrow-derived myogenic progenitors. , 1998, Science.

[10]  Michael Primig,et al.  The Muscle Regulatory Factors MyoD and Myf-5 Undergo Distinct Cell Cycle–specific Expression in Muscle Cells , 1998, The Journal of cell biology.

[11]  R. Armstrong,et al.  Uncoupling of in vivo torque production from EMG in mouse muscles injured by eccentric contractions , 1999, The Journal of physiology.

[12]  T. Nakatsuka,et al.  Postoperative Complications and Functional Results after Total Glossectomy with Microvascular Reconstruction , 2000, Plastic and reconstructive surgery.

[13]  T. Hawke,et al.  Myogenic satellite cells: physiology to molecular biology. , 2001, Journal of applied physiology.

[14]  Klod Kokini,et al.  Morphologic study of small intestinal submucosa as a body wall repair device. , 2002, The Journal of surgical research.

[15]  Gayle M. Smythe,et al.  Notch-Mediated Restoration of Regenerative Potential to Aged Muscle , 2003, Science.

[16]  A. Wernig,et al.  Muscle satellite (stem) cell activation during local tissue injury and repair , 2003, Journal of anatomy.

[17]  B. Olwin,et al.  Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewal. , 2004, Developmental biology.

[18]  M. Rudnicki,et al.  Cellular and molecular regulation of muscle regeneration. , 2004, Physiological reviews.

[19]  Ann E Rundell,et al.  Biaxial strength of multilaminated extracellular matrix scaffolds. , 2004, Biomaterials.

[20]  H. Nakauchi,et al.  Mac-1(low) early myeloid cells in the bone marrow-derived SP fraction migrate into injured skeletal muscle and participate in muscle regeneration. , 2004, Biochemical and biophysical research communications.

[21]  Hung-Chi Chen,et al.  Traumatic major muscle loss in the upper extremity: reconstruction using functioning free muscle transplantation. , 2004, Journal of reconstructive microsurgery.

[22]  E. Chaloner,et al.  Principles of war surgery , 2005, BMJ : British Medical Journal.

[23]  A. Petrie,et al.  Stem Cell Function, Self-Renewal, and Behavioral Heterogeneity of Cells from the Adult Muscle Satellite Cell Niche , 2005, Cell.

[24]  Donald O Freytes,et al.  Esophageal reconstruction with ECM and muscle tissue in a dog model. , 2005, The Journal of surgical research.

[25]  R. Senior,et al.  A Chemotactic Peptide from Laminin α5 Functions as a Regulator of Inflammatory Immune Responses via TNFα-mediated Signaling1 , 2005, The Journal of Immunology.

[26]  T. Rando,et al.  Stem cells in postnatal myogenesis: molecular mechanisms of satellite cell quiescence, activation and replenishment. , 2005, Trends in cell biology.

[27]  M. Mazurek,et al.  The Scope of Wounds Encountered in Casualties From the Global War on Terrorism: From the Battlefield to the Tertiary Treatment Facility , 2006, The Journal of the American Academy of Orthopaedic Surgeons.

[28]  George P McCabe,et al.  Extracellular matrix bioscaffolds for orthopaedic applications. A comparative histologic study. , 2006, The Journal of bone and joint surgery. American volume.

[29]  G. Bowyer Débridement of Extremity War Wounds , 2006, The Journal of the American Academy of Orthopaedic Surgeons.

[30]  Stephen F Badylak,et al.  The extracellular matrix as a biologic scaffold material. , 2007, Biomaterials.

[31]  S. Badylak,et al.  A perivascular origin for mesenchymal stem cells in multiple human organs. , 2008, Cell stem cell.

[32]  S. Badylak,et al.  Macrophage phenotype as a determinant of biologic scaffold remodeling. , 2008, Tissue engineering. Part A.

[33]  Stephen F Badylak,et al.  Immune response to biologic scaffold materials. , 2008, Seminars in Immunology.

[34]  C. Fan,et al.  Functional reconstruction of traumatic loss of flexors in forearm with gastrocnemius myocutaneous flap transfer , 2008, Microsurgery.

[35]  P. Soucacos,et al.  Restoration of elbow function in severe brachial plexus paralysis via muscle transfers. , 2008, Injury.

[36]  John F Kragh,et al.  Combat wounds in operation Iraqi Freedom and operation Enduring Freedom. , 2008, The Journal of trauma.

[37]  S. Badylak,et al.  Increased myocyte content and mechanical function within a tissue-engineered myocardial patch following implantation. , 2009, Tissue engineering. Part A.

[38]  B. Brown,et al.  Evidence of innervation following extracellular matrix scaffold‐mediated remodelling of muscular tissues , 2009, Journal of tissue engineering and regenerative medicine.

[39]  L. McManus,et al.  Bone marrow-derived cell regulation of skeletal muscle regeneration , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[40]  George P McCabe,et al.  Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. , 2009, Biomaterials.

[41]  S. Badylak,et al.  An extracellular matrix scaffold for esophageal stricture prevention after circumferential EMR. , 2008, Gastrointestinal endoscopy.

[42]  V. Agrawal,et al.  Epimorphic regeneration approach to tissue replacement in adult mammals , 2009, Proceedings of the National Academy of Sciences.

[43]  Li Zhang,et al.  Degradation products of extracellular matrix affect cell migration and proliferation. , 2009, Tissue engineering. Part A.

[44]  R. Hoffman,et al.  Mobilization of bone marrow stem cells with StemEnhance improves muscle regeneration in cardiotoxin-induced muscle injury. , 2010, Cell cycle.

[45]  Stephen F Badylak,et al.  Extracellular matrix-derived products modulate endothelial and progenitor cell migration and proliferation in vitro and stimulate regenerative healing in vivo. , 2010, Matrix biology : journal of the International Society for Matrix Biology.

[46]  S. Badylak,et al.  Constructive remodeling of biologic scaffolds is dependent on early exposure to physiologic bladder filling in a canine partial cystectomy model. , 2010, The Journal of surgical research.

[47]  Lorne H Blackbourne,et al.  Characterization of craniomaxillofacial battle injuries sustained by United States service members in the current conflicts of Iraq and Afghanistan. , 2010, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[48]  N. Turner,et al.  Functional skeletal muscle formation with a biologic scaffold. , 2010, Biomaterials.

[49]  D. Weber,et al.  Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction. , 2010, Tissue engineering. Part A.

[50]  V. Agrawal,et al.  Recruitment of progenitor cells by an extracellular matrix cryptic peptide in a mouse model of digit amputation. , 2011, Tissue engineering. Part A.

[51]  S. Badylak,et al.  Extracellular matrix degradation products and low-oxygen conditions enhance the regenerative potential of perivascular stem cells. , 2011, Tissue engineering. Part A.

[52]  J. Hsu,et al.  Volumetric Muscle Loss , 2011, The Journal of the American Academy of Orthopaedic Surgeons.

[53]  A. D. de Vries,et al.  Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice , 2011, Cell transplantation.