Electrospun P(VDF-TrFE)/ceria nanoparticle scaffolds for skeletal muscle regeneration

Schematic illustration of scaffold construction by electrospinning and HA linkage and its application in skeletal muscle regeneration in VML mouse model. • A bioelectronic scaffold combining a piezoelectric polymer and antioxidant nanoparticles was developed for muscle regeneration. • The scaffold enhanced muscle repair by converting mechanical signals into biological stimulation and reducing oxidative stress. • In a preclinical muscle injury model, the scaffold promoted faster functional recovery and more mature muscle fiber formation. • This work demonstrates a synergistic strategy for restoring damaged muscle by integrating bioelectrical stimulation with antioxidant modulation. Volumetric muscle loss (VML) presents a significant clinical challenge due to the limited regenerative capacity of skeletal muscle. Piezoelectric scaffolds have shown promise in enhancing muscle repair by converting mechanical cues into bioelectric signals. In this study, we investigate the regenerative potential of electrospun scaffolds composed of poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] and polycaprolactone (PCL), with or without cerium dioxide nanoparticles (Ce NPs), in a VML mouse model. Hyaluronic acid functionalization was employed to improve scaffold biocompatibility. In vitro experiments confirmed the biocompatibility of these scaffolds, while in vivo assessments over eight weeks demonstrated significant efficacy in restoring muscle function. Compared with PCL-Ce scaffolds, mice implanted with piezoelectric scaffolds exhibited faster grip strength recovery, more mature muscle regeneration, a more hierarchical arrangement of muscle fibers, and increased fiber diameter. Additionally, the antioxidant properties of Ce NPs reduced adipocyte infiltration and excessive collagen deposition and were associated with enhanced angiogenesis. Grip strength measurements further highlighted the superior regenerative performance of P(VDF-TrFE) scaffolds combined with Ce NPs. Overall, these findings underscore the potential of piezoelectric scaffolds integrated with antioxidants in promoting structural and functional muscle regeneration following VML.