Rapid release of growth factors regenerates force output in volumetric muscle loss injuries.
A significant challenge in the design and development of biomaterial scaffolds is to incorporate mechanical and biochemical cues to direct organized tissue growth. In this study, we investigated the effect of hepatocyte growth factor (HGF) loaded, crosslinked fibrin (EDCn-HGF) microthread scaffolds on skeletal muscle regeneration in a mouse model of volumetric muscle loss (VML). The rapid, sustained release of HGF significantly enhanced the force production of muscle tissue 60 days after injury, recovering more than 200% of the force output relative to measurements recorded immediately after injury. HGF delivery increased the number of differentiating myoblasts 14 days after injury, and supported an enhanced angiogenic response. The architectural morphology of microthread scaffolds supported the ingrowth of nascent myofibers into the wound site, in contrast to fibrin gel implants which did not support functional regeneration. Together, these data suggest that EDCn-HGF microthreads recapitulate several of the regenerative cues lost in VML injuries, promote remodeling of functional muscle tissue, and enhance the functional regeneration of skeletal muscle. Further, by strategically incorporating specific biochemical factors and precisely tuning the structural and mechanical properties of fibrin microthreads, we have developed a powerful platform technology that may enhance regeneration in other axially aligned tissues.
Biomedical Engineering Department, Worcester Polytechnic Institute, Worcester, MA 01609, USA; Bioengineering Institute, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
Jonathan M
JM
Grasman
Biomedical Engineering Department, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
Duc M
DM
Do
Biomedical Engineering Department, Worcester Polytechnic Institute, Worcester, MA 01609, USA; Bioengineering Institute, Worcester Polytechnic Institute, Worcester, MA 01609, USA. Electronic address: rpage@wpi.edu.
Raymond L
RL
Page
Biomedical Engineering Department, Worcester Polytechnic Institute, Worcester, MA 01609, USA; Bioengineering Institute, Worcester Polytechnic Institute, Worcester, MA 01609, USA. Electronic address: gpins@wpi.edu.
George D
GD
Pins
D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005337:Fibrin / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D007537:Isometric Contraction / Q000187:drug effects; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D009135:Muscular Diseases / Q000473:pathology / Q000503:physiopathology*; D032446:Myoblasts / Q000187:drug effects / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*
D003432:Cross-Linking Reagents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017228:Hepatocyte Growth Factor; D005337:Fibrin; D003094:Collagen
Fibrin; Hepatocyte growth factor; Microthreads; Muscle regeneration; Tissue engineering