Controlled delivery of PRP from decellularized extracellular matrix enhances skeletal muscle regeneration

The efficacy of platelet-rich plasma (PRP) in enhancing muscle regeneration was limited due to uncontrolled delivery. This study focuses on modification of decellularized scaffolds derived from skeletal muscle extracellular matrix (ECM) by heparin, loading with PRP, to enhance endogenous cell recruitment in muscle regeneration. Here, we showed an optimal decellularization procedure that effectively removed cells while preserving the ECM components in skeletal muscle tissue and the macroporous scaffolds showed suitable physical and mechanical properties for muscle tissue engineering. Heparinized scaffold released platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) in a sustained manner. Moreover, the scaffold increased the metabolic activity and myogenic differentiation of C2C12 cells. In addition, histological analysis revealed higher angiogenesis and more extensive migration of the host muscle cells in the volumetric muscle loss (VML) model. The heparinized scaffold facilitated the attraction and sustained release of growth factors from PRP, which in turn promoted the recruitment of the endothelial and muscle cells in the injured tissue that may have the potential to enhance the accessibility of decellularized scaffolds for off-the-shelf use and to treat muscle defects in clinical practice.