title: A tissue-engineered muscle repair construct for functional restoration of an irrecoverable muscle injury in a murine model.
abstract: There are no effective clinical treatments for volumetric muscle loss (VML) resulting from traumatic injury, tumor excision, or other degenerative diseases of skeletal muscle. The goal of this study was to develop and characterize a more clinically relevant tissue-engineered muscle repair (TE-MR) construct for functional restoration of a VML injury in the mouse lattissimus dorsi (LD) muscle. To this end, TE-MR constructs developed by seeding rat myoblasts on porcine bladder acellular matrix were preconditioned in a bioreactor for 1 week and implanted in nude mice at the site of a VML injury created by excising 50% of the native LD. Two months postinjury and implantation of TE-MR, maximal tetanic force was ∼72% of that observed in native LD muscle. In contrast, injured LD muscles that were not repaired, or were repaired with scaffold alone, produced only ∼50% of native LD muscle force after 2 months. Histological analyses of LD tissue retrieved 2 months after implantation demonstrated remodeling of the TE-MR construct as well as the presence of desmin-positive myofibers, blood vessels, and neurovascular bundles within the TE-MR construct. Overall, these encouraging initial observations document significant functional recovery within 2 months of implantation of TE-MR constructs and provide clear proof of concept for the applicability of this technology in a murine VML injury model.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University Baptist Medical Center, Winston Salem, NC 27157, USA.
authors.forename: Masood A
authors.initials: MA
authors.lastname: Machingal
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Corona
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walters
authors.forename: Venu
authors.initials: V
authors.lastname: Kesireddy
authors.forename: Christine N
authors.initials: CN
authors.lastname: Koval
authors.forename: Ashley
authors.initials: A
authors.lastname: Dannahower
authors.forename: Weixin
authors.initials: W
authors.lastname: Zhao
authors.forename: James J
authors.initials: JJ
authors.lastname: Yoo
authors.forename: George J
authors.initials: GJ
authors.lastname: Christ
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007120:Immunochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D018482:Muscle, Skeletal / Q000166:cytology* / Q000293:injuries* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry