Objectives: This study aims to develop an injectable hydrogel optimized for in situ vocal fold (VF) tissue repair post-defect removal. The ideal hydrogel for this application should (i) cure rapidly to prevent leakage, (ii) adhere strongly to avoid dislodgment, (iii) possess mechanical properties conducive to VF regeneration, (iv) have a microporous structure to support cell infiltration and nutrient/oxygen transport, and (v) contain bioactive properties to promote regenerative healing and minimize fibrosis.
Methods: We synthesized a double-network hydrogel by combining dopamine-grafted hyaluronic acid (DAHA) with silk fibroin (SF), which jellifies rapidly through Fe³⁺-dopamine coordination and is further strengthened by sonication-induced β-sheet formation in SF. Curcumin-loaded polylactic acid (PLA) particles were incorporated to modulate the inflammatory response. The resultant composite hydrogel, designated as Microporous Double Network Composite (MDNC), comprises an optimized blend of curcumin-loaded PLA particles, 2.5% SF, 2.5% DAHA, and 10 mM iron ions. For comparative analysis, three additional formulations were prepared: Nanoporous Single Network (NSN) containing 5% SF, Microporous Single Network (MSN) composed of 5% DAHA, and Microporous Double Network (MDN) with equal parts of SF and DAHA.
Results: SEM and confocal imaging revealed a highly porous MDNC hydrogel (average pore size 110 µm). Rheology showed rapid gelation within 5 s via iron–dopamine coordination and a 50-min stiffening phase from β-sheet formation in silk fibroin. The hydrogel reached a storage modulus of ~1000 Pa and Young’s modulus of ~5 kPa, with full self-healing after deformation. Adhesive strength reached 35 kPa, outperforming fibrin glue. Phalloidin/DAPI staining confirmed healthy fibroblast morphology, and migration assays showed a 19.3 % migration index. Inflammatory assays showed reduced α-SMA and COL1A1 in TGF-β1–stimulated fibroblasts and a 2.9-fold increase in CD206 in macrophages, indicating M2 polarization.
Conclusions: The microporous double-network composite (MDNC) hydrogel supports in situ tissue repair with strong adhesion, cell infiltration, and mechanical resilience. Sustained curcumin release promotes M2 macrophage polarization while suppressing fibrosis through inhibition of TGF-β1–induced myofibroblast differentiation. This combination of mechanical, structural, and immunomodulatory properties positions MDNC as a promising material for repairing dynamic tissues.