In vitro evaluation of functionalized decellularized muscle scaffold for in situ skeletal muscle regeneration

Abstract

Current treatment options for repairing volumetric muscle loss injury involve the use of existing host tissue like muscular flaps or grafts. However, host muscle tissue may not be available and donor site morbidity, such as functional loss and volume deficiency, is often present. In this study, we developed a biofunctionalized muscle-derived decellularized extracellular matrix scaffolding system to utilize endogenous stem/progenitor cells for in situ muscle tissue regeneration. We optimized the decellularization process to enhance cellular infiltration and fabricated an insulin-like growth factor-binding protein 3 (IGFBP-3)-conjugated scaffold for controlled delivery of IGF-I. We then tested in vitro characterization including IGF-I release kinetics and cellular infiltration. In addition, we have analyzed the bioactivities of skeletal muscle cells (C2C12) to assess the indirect effect of released IGF-1 from the scaffold. The IGFBP-3 conjugated scaffolds demonstrated showed sustained release of IGF-1 and 1% SDS decellularized scaffold with IGF-1 showed higher cellular infiltration compared to control scaffolds (no conjugation). In indirect bioactivity assay, IGF-1 conjugated scaffold showed 2.1-fold increased cell activity compared to control (fresh media). Our results indicate that IGFBP-3/IGF-I conjugated scaffold has the potential to be used for in situ muscle tissue regeneration.