An Adhesive Aminated Silk Fibroin/Oxidized Alginate Hybrid Hydrogel with Intrinsic Material-Driven Immunomodulatory and Proangiogenic Activities

Effective wound healing requires the coordinated regulation of inflammatory responses and vascular remodeling. However, many bioactive wound dressings rely on exogenous growth factors, therapeutic agents, or cells, which increases formulation complexity and hinders clinical translation. Whether adhesive biomaterials can intrinsically modulate the immune and vascular microenvironments remains poorly understood. Herein, we investigated the intrinsic bioactivity of an adhesive hydrogel composed of aminated silk fibroin and oxidized alginate (ASF/OA), dynamically crosslinked via Schiff-base reactions without any exogenous bioactive additives. Its immunomodulatory and angiogenic potential was evaluated using macrophage assays and the chick chorioallantoic membrane (CAM) model. The ASF/OA hydrogel suppressed tumor necrosis factor-alpha (TNF-α) secretion in a concentration-dependent manner (greater than 90% inhibition at 300 mg mL-1) while upregulating arginase-1 (Arg1) expression at 200-300 mg mL-1, indicating modulation toward a reparative macrophage activation state. Furthermore, the hydrogel promoted macrophage migration, evidenced by pronounced cell elongation and remodeled F-actin cytoskeletal organization. The hydrogel also exhibited no detectable irritation in the hen's egg test (HET)-CAM assay. In the CAM model, ASF/OA significantly increased the number of blood vessels and the vascular index. Histological evaluation revealed host cell infiltration into the peripheral region of the hydrogel, blood vessels beneath and adjacent to the implant, and a continuous hydrogel-CAM interface without obvious fibrous separation. These findings demonstrate that the ASF/OA hydrogel intrinsically modulates macrophage behavior in vitro and enhances neovascularization in the CAM model, effects attributed to its physicochemical and adhesive interfacial properties. This work establishes a simplified, material-driven paradigm for designing multifunctional adhesive biomaterials without relying on external bioactive cues. Further validation using in vivo wound models is warranted to assess the potential of ASF/OA for tissue regeneration.