Aligned Collagen Sponges Loaded With Myogenic Factors to Enhance Skeletal Muscle Tissue Regeneration.

Volumetric muscle loss (VML) is an injury which leads to debilitating loss of functionality of a muscle. Autologous tissue grafts are used as a standard treatment; however, these grafts often result in complications. Current scaffolds are limited in their ability to restore functionality of the injured muscle, which may be due to lack of cell recruitment to the scaffold and/or lack of sufficient myofiber formation. Our approach involves the controlled release of insulin-like growth factor-1 (IGF-1) from a biopolymer scaffold, as IGF-1 enhances both the proliferation and differentiation of myoblasts, which we hypothesize will enhance regeneration after VML. In this study, to facilitate a more controlled release of IGF-1, we added IGF-binding protein 5 (IGFBP-5) to anisotropic collagen sponges with finely tuned pore sizes via heparin conjugation to stabilize the IGFBP-5/IGF-1 complex. Scaffolds containing heparin, IGFBP-5, and IGF-1 induced the highest level of myofiber formation for up to 4 weeks, suggesting this scaffold system supported the sustained release of active IGF-1. Future studies will be used to implant these scaffolds into mouse models of VML and determine their effects on regeneration in vivo as well as on restoration of force production of the muscle.