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Strontium-crosslinked potassium-alginate beads as coordination-driven ion-exchange biomaterials for regenerative
Yueh-Teng Tsai1, Hsin-Chien Chen2, Chih-Hung Wang3
1Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 320317, Taiwan, ROC.
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Biological macromolecule-based biomaterials have emerged as versatile platforms for controlled delivery and microenvironmental regulation in regenerative medicine. Among them, polysaccharide-derived systems offer unique advantages in biocompatibility, tunability, and sustainability. Here, we report a biomacromoleculebased coordination-driven ion-exchange biomaterial platform using strontiumcrosslinked potassium alginate beads (K+-beads), designed to dynamically regulate Na+/K+ homeostasis and reconstruct physiologically relevant ionic microenvironments. The K+-beads exhibit a core-shell architecture consisting of a semi-permeable Sr2+-crosslinked alginate membrane and a semi-gelled K+-alginate core, enabling reversible and programmable Na+/K+ exchange and selective sodium uptake under osmotic equilibrium. Physicochemical characterization demonstrates tunable ion-exchange kinetics, structural stability, and acceptable cytocompatibility. Functionally, this platform operates as a dynamic ion-delivery system that establishes a progressive high-K+/low-Na+ microenvironment, thereby mimicking key ionic characteristics associated with cochlear endolymph development. When applied to cochlear progenitor cell cultures, the ion-regulated microenvironment significantly enhances hair-cell-like (HC-like) differentiation, as evidenced by stage-specific expression of Sox-2, Atoh1, and MYO7A. Beyond ionic regulation, the K+-beads reduce nitrogenous metabolic waste, supporting long-term culture stability and compatibility with perfusion-based systems. Collectively, this study establishes alginate-based ion-exchange biomaterials as multifunctional platforms for regulating biochemical and biophysical cues in regenerative systems. This work highlights the potential of biological macromoleculederived materials in advancing next-generation regenerative and biomimetic culture systems through dynamic microenvironment engineering.
