Peptide-conjugated alginate fiber: A skeletal muscle regenerative scaffold

Biopolymeric fibers have garnered significant attention in biomedical applications due to their ability to promote tissue regeneration through aligned microstructures. Alginate (Alg) is commonly used to prepare wet-spun fibers through ionic interactions. However, ion-crosslinked Alg fibers present limitations in tissue regeneration due to their rapid degradation under physiological conditions and the absence of binding sites for bioactive molecules. In this study, oxidized methacrylated alginate (OMA) derivatives were synthesized to create Alg fibers crosslinked by both Ca²⁺ ions and photo-initiated covalent bonds. Moreover, aldehyde groups introduced on the oxidized chains facilitate covalent conjugation of bioactive molecules via Schiff base reactions. As a model bioactive factor, C domain peptide of insulin-like growth factor-1 (IGF-1C) was conjugated to fibers, and the resulting fibers (OMA-P) were evaluated for their potential in muscle regeneration. Cell experiments showed that OMA-P fibers promoted C2C12 myoblast proliferation and guided their oriented growth. In rat volume muscle loss (VML) models, OMA-P fibers significantly improved muscle regeneration compared to peptide-free OMA fibers and OMA-P sponges without aligned structure, because of the dual effects of axial guidance cue and bioactive peptide conjugation. This study presents a novel method for fabricating bioactive fibers, highlighting their potential as structured scaffolds for regenerative medicine.