An Autologous Muscle Tissue Expansion Approach for the Treatment of Volumetric Muscle Loss

Abstract Volumetric muscle loss (VML) is a hallmark of orthopedic trauma with no current standard of care. As a potential therapy for some VML indications, autologous minced muscle grafts (1 mm3 pieces of muscle) are effective in promoting remarkable de novo fiber regeneration. But they require ample donor muscle tissue and therefore may be limited in their application for large clinical VML. Here, we tested the hypothesis that autologous minced grafts may be volume expanded in a collagen hydrogel, allowing for the use of lesser autologous muscle while maintaining regenerative and functional efficacy. The results of the study indicate that 50% (but not 75%) less minced graft tissue suspended in a collagen hydrogel promoted a functional improvement similar to that of a 100% minced graft repair. However, approximately half of the number of fibers regenerated de novo with 50% graft repair. Moreover, the fibers that regenerated had a smaller cross-sectional area. These findings support the concept of using autologous minced grafts for the regeneration of muscle tissue after VML, but indicate the need to identify optimal carrier materials for expansion.

[1]  B. Carlson The regeneration of minced muscles. , 1972, Monographs in developmental biology.

[2]  T. Walters,et al.  Autologous minced muscle grafts: a tissue engineering therapy for the volumetric loss of skeletal muscle. , 2013, American journal of physiology. Cell physiology.

[3]  G. Maréchal,et al.  The origin of muscle stem cells in rat triceps surae regenerating after mincing , 1984, Journal of Muscle Research & Cell Motility.

[4]  D. Lindquist,et al.  Muscle-specific atrophy of the quadriceps femoris with aging. , 2001, Journal of applied physiology.

[5]  T. Walters,et al.  Muscle-derived decellularised extracellular matrix improves functional recovery in a rat latissimus dorsi muscle defect model. , 2013, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[6]  P. Chao,et al.  The influence and interactions of substrate thickness, organization and dimensionality on cell morphology and migration. , 2013, Acta biomaterialia.

[7]  D. Weber,et al.  Biologic scaffold remodeling in a dog model of complex musculoskeletal injury. , 2012, The Journal of surgical research.

[8]  R. Lieber,et al.  Skeletal muscle fibrosis develops in response to desmin deletion. , 2012, American journal of physiology. Cell physiology.

[9]  Will L. Johnson,et al.  A three-dimensional model of the rat hindlimb: musculoskeletal geometry and muscle moment arms. , 2008, Journal of biomechanics.

[10]  A. R. Baker,et al.  Investigating muscle regeneration with a dermis/small intestinal submucosa scaffold in a rat full-thickness abdominal wall defect model. , 2015, Journal of biomedical materials research. Part B, Applied biomaterials.

[11]  Roman A Hayda,et al.  The Military Extremity Trauma Amputation/Limb Salvage (METALS) study: outcomes of amputation versus limb salvage following major lower-extremity trauma. , 2013, The Journal of bone and joint surgery. American volume.

[12]  J. Alcaraz,et al.  Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin β1 , 2013, Journal of Cell Science.

[13]  B. Sicari,et al.  A murine model of volumetric muscle loss and a regenerative medicine approach for tissue replacement. , 2012, Tissue engineering. Part A.

[14]  J. Hsu,et al.  Does the Zone of Injury in Combat-Related Type III Open Tibia Fractures Preclude the Use of Local Soft Tissue Coverage? , 2010, Journal of orthopaedic trauma.

[15]  Kerry A. Daly,et al.  Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. , 2012, Acta biomaterialia.

[16]  T. Walters,et al.  Implantation of in vitro tissue engineered muscle repair constructs and bladder acellular matrices partially restore in vivo skeletal muscle function in a rat model of volumetric muscle loss injury. , 2013, Tissue engineering. Part A.

[17]  B. Carlson,et al.  Development of contractile properties of minced muscle regenerates in the rat. , 1972, Experimental neurology.

[18]  M. H. Snow Metabolic activity during the degenerative and early regenerative stages of minced skeletal muscle , 1973, The Anatomical record.

[19]  T. Walters,et al.  Repair of traumatic skeletal muscle injury with bone-marrow-derived mesenchymal stem cells seeded on extracellular matrix. , 2010, Tissue engineering. Part A.

[20]  Youn Hwan Kim,et al.  Coverage of Amputation Stumps Using a Latissimus Dorsi Flap With a Serratus Anterior Muscle Flap: A Comparative Study , 2016, Annals of plastic surgery.

[21]  Masood A. Machingal,et al.  A tissue-engineered muscle repair construct for functional restoration of an irrecoverable muscle injury in a murine model. , 2011, Tissue engineering. Part A.

[22]  Maximilian Rudert,et al.  A Prospective Multicenter Study on the Outcome of Type I Collagen Hydrogel–Based Autologous Chondrocyte Implantation (CaReS) for the Repair of Articular Cartilage Defects in the Knee , 2011, The American journal of sports medicine.

[23]  V. Edgerton,et al.  Physiological cross‐sectional area of human leg muscles based on magnetic resonance imaging , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[24]  T. Walters,et al.  Functional assessment of skeletal muscle regeneration utilizing homologous extracellular matrix as scaffolding. , 2010, Tissue engineering. Part A.

[25]  B. Malissen,et al.  Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration , 2011, Development.

[26]  T Guda,et al.  Transplantation and perfusion of microvascular fragments in a rodent model of volumetric muscle loss injury. , 2014, European cells & materials.

[27]  C. Rathbone,et al.  Transplantation of devitalized muscle scaffolds is insufficient for appreciable de novo muscle fiber regeneration after volumetric muscle loss injury , 2014, Cell and Tissue Research.

[28]  H. Blau,et al.  IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors , 2005, The Journal of cell biology.

[29]  J. Alcaraz,et al.  Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin β1 , 2013, Development.

[30]  J. Fridén,et al.  Functional and clinical significance of skeletal muscle architecture , 2000, Muscle & nerve.

[31]  E. Schultz,et al.  Response of satellite cells to focal skeletal muscle injury , 1985, Muscle & nerve.

[32]  Yu-Te Lin,et al.  Free Functioning Muscle Transfer for Lower Extremity Posttraumatic Composite Structure and Functional Defect , 2007, Plastic and reconstructive surgery.

[33]  D. Dudek,et al.  Designed biomaterials to mimic the mechanical properties of muscles , 2010, Nature.

[34]  J. Faulkner,et al.  Whole skeletal muscle transplantation: Mechanisms responsible for functional deficits , 1994, Biotechnology and bioengineering.

[35]  S. Badylak,et al.  Clinical application of an acellular biologic scaffold for surgical repair of a large, traumatic quadriceps femoris muscle defect. , 2010, Orthopedics.

[36]  N. Epstein A Preliminary Study of the Efficacy of Beta Tricalcium Phosphate as a Bone Expander for Instrumented Posterolateral Lumbar Fusions , 2006, Journal of spinal disorders & techniques.

[37]  G. Lose,et al.  Intraurethral injection of autologous minced skeletal muscle: a simple surgical treatment for stress urinary incontinence. , 2014, The Journal of urology.

[38]  F. Camargo,et al.  Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates , 2003, Nature Medicine.

[39]  Douglas J. Weber,et al.  An Acellular Biologic Scaffold Promotes Skeletal Muscle Formation in Mice and Humans with Volumetric Muscle Loss , 2014, Science Translational Medicine.

[40]  T. Walters,et al.  Losartan administration reduces fibrosis but hinders functional recovery after volumetric muscle loss injury. , 2014, Journal of applied physiology.

[41]  M. Conconi,et al.  Experimental abdominal wall defect repaired with acellular matrix , 2002, Pediatric Surgery International.

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

[43]  J. Wilken,et al.  Volumetric muscle loss: Persistent functional deficits beyond frank loss of tissue , 2015, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[44]  B. Bailey,et al.  Latissimus dorsi muscle free flaps. , 1982, British journal of plastic surgery.

[45]  T. Walters,et al.  The promotion of a functional fibrosis in skeletal muscle with volumetric muscle loss injury following the transplantation of muscle-ECM. , 2013, Biomaterials.

[46]  N. Epstein Efficacy of different bone volume expanders for augmenting lumbar fusions. , 2008, Surgical neurology.

[47]  B. Carlson,et al.  Regeneration of the completely excised gastrocnemius muscle in the frog and rat from minced muscle fragments , 1968, Journal of morphology.

[48]  M. Archdeacon,et al.  Autogenous bone graft: donor sites and techniques. , 2011, The Journal of bone and joint surgery. American volume.

[49]  G. Maréchal,et al.  Implantation of autologous cells in minced and devitalized rat skeletal muscles , 1986, Journal of Muscle Research & Cell Motility.