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 <i>n</i> = 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. <i>In vivo</i>, 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 <i>via</i> 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. HIGHLIGHTSA quantitative correlation (<i>R</i>² > 0.94) was established between dual-ion crosslink density and hydrogel mechanical strength, enabling rational engineering of natural-polymer dressings.Achieved unprecedented thermal stability (initial decomposition 255.8 °C), surpassing autoclave requirements and solving a long-standing translational barrier.pH-triggered anomalous transport accelerated metformin release by 19.5 % at pH 5.5 (infected wound) versus pH 7.4, outperforming commercial Aquacel® Ag.In vivo rat model showed 94 % wound closure in 14 days, zero infection incidence, and favorable immunomodulation (38 % TNF-α reduction, 2× IL-10 increase).