Ionic interactions and cross-linking mechanisms in freeze-dried alginate xerogels: A microstructural and...

Alginate xerogels represent a class of ultralightweight, highly porous materials that offer structural stability and active surfaces features frequently lacking in conventional hydrogels. However, achieving optimal biological and mechanical performance requires a comprehensive understanding of their ionic cross-linking mechanisms. This study investigates the impact of calcium (Ca²⁺), cobalt (Co²⁺), zinc (Zn²⁺) ions, and their binary mixtures on the microstructural evolution and functional versatility of alginate xerogels designed for tissue engineering. The transition to the xerogel state preserves a three-dimensional, interconnected porous architecture that facilitates nutrient exchange and guided cellular infiltration. X-ray photoelectron spectroscopy (XPS) revealed distinct chemical shifts depending on the cross-linking agent: Ca²⁺ promotes a predominantly ionic character (530.46 eV), whereas Co²⁺ and Zn²⁺ facilitate coordination bonding with partial covalent features. This distinction at the atomic level directly dictates the macroscopic and structural behavior of the matrix. Microcomputed tomography (μCT) and scanning electron microscopy (SEM) confirmed that calcium ions yield dense, cohesive networks with high pore connectivity, rendering them suitable for load-bearing applications. In contrast, Co²⁺ and Zn²⁺ promote open, anisotropic architectures with exceptional water absorption capacities (>3000%), while partially preserving the original fiber orientation and crystallinity. Ultimately, the synergistic use of ionic mixtures proved to be an effective strategy for tuning the porosity and anisotropy of sodium alginate xerogel matrices. These structures can be tailored for diverse therapeutic applications, ranging from angiogenesis-inducing scaffolds to advanced antimicrobial dressings.