title: Restoration of skeletal muscle defects with adult human cells delivered on fibrin microthreads.
abstract: Large-scale musculoskeletal wounds, such as those seen in trauma injuries, present poor functional healing prognoses. In severe trauma, when the native tissue architecture is destroyed or lost, the regenerative capacity of skeletal muscle is diminished by scar formation. Here we demonstrate that a scaffold system composed of fibrin microthreads can provide an efficient delivery system for cell-based therapies and improve regeneration of a large defect in the tibialis anterior of the mouse. Cell-loaded fibrin microthread bundles implanted into a skeletal muscle resection reduced the overall fibroplasia-associated deposition of collagen in the wound bed and promoted in-growth of new muscle tissue. When fibrin microthreads were seeded with adult human cells, implanted cells contributed to the nascent host tissue architecture by forming skeletal muscle fibers, connective tissue, and PAX7-positive cells. Stable engraftment was observed at 10 weeks postimplant and was accompanied by reduced levels of collagen deposition. Taken together, these data support the design and development of a platform for microthread-based delivery of autologous cells that, when coupled to an in vitro cellular reprogramming process, has the potential to improve healing outcomes in large skeletal muscle wounds.
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts 01609, USA. rpage@wpi.edu
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Page
authors.forename: Christopher
authors.initials: C
authors.lastname: Malcuit
authors.forename: Lucy
authors.initials: L
authors.lastname: Vilner
authors.forename: Ina
authors.initials: I
authors.lastname: Vojtic
authors.forename: Sharon
authors.initials: S
authors.lastname: Shaw
authors.forename: Emmett
authors.initials: E
authors.lastname: Hedblom
authors.forename: Jason
authors.initials: J
authors.lastname: Hu
authors.forename: George D
authors.initials: GD
authors.lastname: Pins
authors.forename: Marsha W
authors.initials: MW
authors.lastname: Rolle
authors.forename: Tanja
authors.initials: T
authors.lastname: Dominko
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005337:Fibrin / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005337:Fibrin