3D bioprinted alginate/gelatin hydrogel: concentration modulated properties toward scar-minimized wound healing

Abstract

The critical shortage of transplantable skin remains a leading cause of mortality in patients with severe skin injuries, driving the demand for advanced 3D-bioprinted constructs. While hydrogel-based bioinks are pivotal for skin tissue engineering, existing systems often fail to simultaneously address biomechanical compatibility, scar suppression, and cell viability. Here, we propose a rationally designed sodium alginate/gelatin (SA/Gel) hydrogel platform through composition-property-performance correlation analysis. Systematic characterization revealed that increasing gelatin content (8-12 wt%) enhanced viscosity (by 2.5-fold), compressive modulus (25.6 ± 2.7 kPa to 37.9 ± 3.5 kPa), tensile fracture elongation (57.9 ± 4.2% to 92.1 ± 1.3%), and print fidelity, while reducing degradation ratio (62.8 ± 2.9% to 26.4 ± 2.4% at day 14) and pore size (128.5 ± 16.6 μm to 79.4 ± 19.7 μm). The optimized A4G10 formulation exhibited synergistic advantages: (1) dynamic swelling (36.3 ± 0.8%) balanced nutrient permeation with structural stability; (2) tunable degradation (47.2% at day 14) matched neo-tissue formation; (3) anisotropic mechanical properties (compressive modulus 32.2 ± 4.1 kPa, tensile modulus 31.7 ± 3.9 kPa) mimicked native skin mechanics; (4) sub-100 μm porous architecture (102.9 ± 12.4 μm) effectively suppressed fibroblast over--proliferation. Remarkably, the SA/Gel scaffolds maintained 98% cell viability (Live/Dead assay) in vitro, while suppressing fibrotic tissue formation and facilitating angiogenesis in vivo. This multi-functional SA/Gel system demonstrates unprecedented potential as a scar--inhibiting bioink for clinical-grade skin regeneration.