Poisson's Ratio‐Driven Control of Myogenic Differentiation and Maturation in Auxetic Metamaterials under Dynamic Mechanical Stimulation

Skeletal muscle regeneration requires scaffolds that accommodate the remarkable mechanical heterogeneity of different muscle types while supporting tissue development. Auxetic metamaterials—structures with negative Poisson's ratio that expand laterally when stretched—offer superior mechanical properties including enhanced energy absorption and high yield strain capacity. However, their effects on muscle differentiation under dynamic loading remain unexplored. This study systematically investigated how Poisson's ratio influences skeletal muscle development by designing, fabricating, and mechanically characterizing nine auxetic geometries via melt extrusion printing with a medical‐grade poly(L‐lactide‐co‐ε‐caprolactone) (PLLA/PCL) copolymer copolymer (PLC). Three geometries with distinct Poisson's ratios (tetrachiral ≈ 0, arrowhead ≈ −0.3, Lozenge ≈ −0.68) were selected for biological evaluation. The auxetic scaffolds were loaded with C2C12 myoblasts encapsulated in fibrin hydrogels and underwent cyclic tensile strain (0%–3%) for 3 h daily over 10 days. Gene expression analysis revealed geometry‐dependent differences in differentiation and fiber‐type commitment that were associated with distinct Poisson's ratio profiles. By comparing scaffold geometries spanning a broad range of Poisson's ratio values while maintaining similar constituent material and fabrication conditions, this work demonstrates that negative Poisson's ratio and the mechanical environments generated by auxetic architectures may represent important mechanobiological cues for skeletal muscle engineering.