A 3D-printed spider silk-based functional mesh for ventral hernia repair via endogenous regeneration-promoting strategies.

Ventral hernia, a prevalent condition especially in the elderly, is primarily treated with mesh implantation. However, high postoperative recurrence persists due to mismatched degradation rates of biological meshes and tissue remodeling. We engineered an electrospun composite mesh (CPCM) integrating chitosan, polylactic acid, and chimeric mini-spidroin recombinant collagen to address this challenge. Methods: The CPCM was fabricated by combining 3D printing with bilateral electrospinning. Fourier-transform infrared spectroscopy, scanning electron microscopy, water contact-angle measurements, degradation assays, and uniaxial tensile testing were used to characterize its physicochemical and mechanical properties. Cytocompatibility, cell adhesion, antibacterial activity, and angiogenic effects were evaluated in vitro. A rat abdominal wall defect model was used to assess biocompatibility, vascularization, collagen remodeling, and repair efficacy through histological staining, immunofluorescence, Western blotting, and qRT-PCR. Results: The CPCM exhibited favorable physicochemical and mechanical properties, gradual degradation, satisfactory cytocompatibility, enhanced cell adhesion, and significant antibacterial activity. CPCM implantation was associated with a repair-associated macrophage response and increased vascular density and vascular maturation during the early repair phase. At 12 weeks, the CPCM group exhibited greater collagen deposition, a higher collagen I/III ratio, more coherently organized collagen bundles, and improved mechanical performance of the repaired abdominal wall. In vitro molecular analyses further supported the involvement of TGF-β/Smad signaling in the fibroblast response to CPCM. Conclusion: CPCM demonstrated favorable physicochemical properties, antibacterial activity, and biocompatibility, and supported vascularization, repair-associated macrophage responses and collagen remodeling during abdominal wall repair. These findings suggest that CPCM may provide a promising multifunctional biodegradable mesh for abdominal wall reconstruction, while the contribution of TGF-β/Smad signaling to its regenerative effects warrants further investigation.