Multifunctional Double-Network Hydrogel with Porous, Adhesive, and Immunomodulatory Properties for Minimally Invasive...

The minimally invasive repair of soft tissue defects remains a major clinical challenge due to the lack of biomaterials that simultaneously fulfill key requirements, including extrudability, strong adhesion, seamless integration, bioactivity, and appropriate mechanical properties. Here, a multifunctional double-network composite hydrogel is presented that is synthesized from modified hyaluronic acid (HA) and silk fibroin (SF) through a stepwise gelation process. The incorporation of ferric ions enables dynamic crosslinking of dopamine-grafted HA, resulting in the rapid formation of adhesive hydrogels with microporous structures. Sonication-induced β-sheets in SF form a secondary network, enhancing mechanical strength with reduced swelling and degradation. The inclusion of curcumin-loaded particles within the hydrogel promotes anti-inflammatory and antifibrotic activity by promoting macrophage polarization toward the reparative M2 phenotype and reducing TGF-β-induced fibroblast differentiation and collagen deposition. In situ injectability and printability of the hydrogel are demonstrated in ex vivo porcine vocal fold models. In vitro and in vivo biological evaluations in rat models confirm the cytocompatibility of the hydrogel and its ability to support cell penetration. Mechanical, structural, and biological results collectively support the applicability of this hydrogel as a minimally invasive solution for soft tissue defect repair, particularly in mechanically dynamic tissues such as the human vocal folds.