High-performance ionic conductive 3d-printed cell-free hydrogel for soft tissue engineering scaffolds

Soft tissue injury and degeneration are prevalent clinical challenges that often require surgical intervention or implantation of biomaterials. Scaffold-based tissue engineering offers a compelling solution, particularly with 3D-printable designs that enable patient-specific customization and complex architecture replication. Nevertheless, current scaffolds often lack tunability, particularly in balancing ionic conductivity and compressive strength, as improving one typically compromises the other, limiting their effectiveness across various tissue types. To overcome these limitations, this study introduces a cell-free hydrogel scaffold fabricated via direct ink writing (DIW), incorporating physical–ionic crosslinking and shear-induced alignment of sulfonated cellulose nanocrystals (CNC). The resulting anisotropic porous architecture enhances ionic conductivity and mechanical performance. Post-printing treatments, including freeze–thaw (FT)–induced crystallization and Hofmeister ion-mediated salting-out, further enhance compressive modulus, degradation stability, and ethanol sterilizability, thereby enabling long-term storage. A multicomponent single-ink formulation allows precise tuning of scaffold properties through controlled post-processing, supporting application across diverse soft tissues. Furthermore, in vitro assays confirm biocompatibility and cell attachment. By integrating sustainable materials, room-temperature processing, and a humectant-free formulation, this work offers a scalable and clinically relevant platform for fabricating soft, ionically conductive biomaterials.