Enhancing cell recruitment onto crosslinked fibrin microthreads with hepatocyte growth factor

Volumetric muscle loss (VML) defects caused by major trauma lead to loss of muscle mass, mobility, and ultimately may result in tissue morbidity. These large-scale injuries destroy native tissue structures such as the basal lamina, which serves as a regenerative template for muscle regeneration. Our approach to the regeneration of VML injuries is to use fibrin microthreads, scaffolds with similar morphology to native muscle, and modulate their mechanical and structural properties to recapitulate cues lost with the destruction of native tissue structures. In this study, we investigated the effect of adsorbing hepatocyte growth factor (HGF) onto crosslinked microthreads on myoblast proliferation and recruitment in an in vitro model designed to mimic in vivo satellite cell recruitment and found that active HGF is released for 1-2 days and is capable of stimulating myoblast migration in both 2D and 3D models. These data suggest that HGF-adsorbed microthreads can recruit myoblasts to the wound site, ultimately leading to an enhanced regenerative response in VML injuries.