International Journal of Biological Macromolecules, cilt.360, 2026 (SCI-Expanded, Scopus)
Alginate, a natural polysaccharide [(1 → 4)-linked β-D-mannuronate and α-L-guluronate], is commonly used in hydrogel form in the biomedical field, including wound healing, drug delivery, and tissue engineering applications. The type and density of cross-linking are key parameters determining the physicochemical and mechanical properties of the hydrogel. However, most of the crosslinking reagents used are generally toxic, requiring extensive modifications and limiting their applicability. Alginate readily forms ionic hydrogels through coordination with divalent cations such as Ca2+ and Ba2+; however, these physically crosslinked networks exhibit poor mechanical integrity under aqueous and in-vivo conditions. Consequently, there is a critical demand for cross-linking agents that are biocompatible, non-toxic, hydrolytically stable, rapidly gelling, and cost-effective to overcome these limitations. In this study, alginate-based 3D hydrogel scaffolds were prepared in a completely green synthetic way using caffeine-catalyzed citric acid (CA)-poly(ethylene glycol) (PEG)/poly(propylene glycol) (PPG) as the cross-linker system. The thermal stability, swelling, rheology as well as compressive strength of the hydrogels were investigated and optimized. The developed hydrogel scaffolds containing PPG withstood compressive deformation in both dry and swollen states without any damage and recovered their initial shape after unloading, indicating that the hydrogels possess a certain shape recovery property. In-vitro biological studies with human adipose stem cells revealed that both scaffold types were cytocompatible and showed good hemocompatibility. Overall, the green synthesis of biocompatible and mechanically resilient alginate-CA-PPG scaffolds highlights their potential as versatile biomaterials for prospective medical applications, particularly in soft tissue engineering.