Synergistic Effects of Zn ²⁺ /Ca ²⁺ Crosslinking on Alginate-Chitosan Semi-Interpenetrating Networks: Mechanical and pH Responsive Properties

Zn²⁺/Ca²⁺ synergistic crosslinking was engineered in chitosan-alginate semi-interpenetrating networks (semi-IPNs) to establish crosslinking density (15.2-58.3 mol/m³) as a predictive parameter for multi-scale hydrogel performance. Fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) analyses confirmed Zn²⁺ ions coordination bonding with chitosan amines, synergizing with Ca²⁺-alginate ionic bridges to significantly enhance thermal stability (initial decomposition temperature increased to 255.8 °C; final decomposition temperature elevated to 490.6 °C) and mechanical properties (tensile strength improved 615% to 12.9 MPa; compressive strength increased 350% to 1.8 MPa). Morphological refinement reduced pore size to 24.3 μm and porosity to 56.9%, enabling pH-responsive swelling where the equilibrium swelling ratio at pH 5.5 exceeded pH 7.4 values by 52%. Anomalous non-Fickian drug release (Korsmeyer-Peppas exponent n = 0.47-0.66) facilitated infection-targeted delivery, with metformin release at pH 5.5 reaching 78.2% compared to 58.7% at pH 7.4. In vivo, the optimized 10 mM Zn²⁺ ions/10 mM Ca²⁺ ions system (F5) accelerated wound healing to 94.2% closure by day 14, eliminated infection incidence, and promoted immunomodulation (38.2% reduction in TNF-α; 2.1-fold increase in IL-10) through degradation-matched tissue regeneration. Validated via multi-technique characterization, this dual-ion platform resolves historical trade-offs in natural polymer hydrogels, offering a predictive design paradigm for advanced wound dressings and stimuli-responsive drug delivery.