Conformation-Dependent Regenerative Effects of PDRN in 3D-Bioprinted Muscle Scaffolds

Volumetric muscle loss (VML) remains a major challenge in skeletal muscle regeneration. In this study, native polydeoxyribonucleotide (PDRN) was structurally engineered into double-stranded polydeoxyribonucleotide (dsPDRN) and single-stranded polydeoxyribonucleotide (ssPDRN) through ultrasound (US)-assisted fragmentation and thermal denaturation. The processed PDRNs were incorporated into UV-crosslinked gelatin methacryloyl (GelMA) bioinks to fabricate 3D bioprinted muscle scaffolds. Notably, ssPDRN-containing hydrogels exhibited enhanced pore remodeling, myogenic differentiation, and muscle regeneration compared with dsPDRN. These findings suggest that the structural conformation of PDRN critically influences the regenerative performance of GelMA-based muscle scaffolds.