title: Biologic-free mechanically induced muscle regeneration.
abstract: Severe skeletal muscle injuries are common and can lead to extensive fibrosis, scarring, and loss of function. Clinically, no therapeutic intervention exists that allows for a full functional restoration. As a result, both drug and cellular therapies are being widely investigated for treatment of muscle injury. Because muscle is known to respond to mechanical loading, we investigated instead whether a material system capable of massage-like compressions could promote regeneration. Magnetic actuation of biphasic ferrogel scaffolds implanted at the site of muscle injury resulted in uniform cyclic compressions that led to reduced fibrous capsule formation around the implant, as well as reduced fibrosis and inflammation in the injured muscle. In contrast, no significant effect of ferrogel actuation on muscle vascularization or perfusion was found. Strikingly, ferrogel-driven mechanical compressions led to enhanced muscle regeneration and a ∼threefold increase in maximum contractile force of the treated muscle at 2 wk compared with no-treatment controls. Although this study focuses on the repair of severely injured skeletal muscle, magnetically stimulated bioagent-free ferrogels may find broad utility in the field of regenerative medicine.
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Wyss Institute for Biologically Inspired Engineering, Cambridge, MA 02138;
authors.forename: Christine A
authors.initials: CA
authors.lastname: Cezar
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Wyss Institute for Biologically Inspired Engineering, Cambridge, MA 02138;
authors.forename: Ellen T
authors.initials: ET
authors.lastname: Roche
authors.affiliation: Department of Pathology and Lab Medicine, Brown University, Providence, RI 02912;
authors.forename: Herman H
authors.initials: HH
authors.lastname: Vandenburgh
authors.affiliation: Julius Wolff Institute, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, 13353 Berlin, Germany.
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Wyss Institute for Biologically Inspired Engineering, Cambridge, MA 02138;
authors.forename: Conor J
authors.initials: CJ
authors.lastname: Walsh
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Wyss Institute for Biologically Inspired Engineering, Cambridge, MA 02138; mooneyd@seas.harvard.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000818:Animals; D001688:Biological Products / Q000494:pharmacology; D001696:Biomechanical Phenomena / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D005355:Fibrosis; D005782:Gels; D006614:Hindlimb / Q000473:pathology; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D060328:Magnetic Phenomena; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D010100:Oxygen / Q000494:pharmacology; D010477:Perfusion; D012038:Regeneration
chemical_list: D001688:Biological Products; D005782:Gels; D010100:Oxygen
keywords: fibrous capsule; immunomodulation; magnetic hydrogel; massage-mimetic; mechano-therapy
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