Understanding alginate-based hydrogels and their crosstalk with cells

Hydrogels are high-water-content materials formed from crosslinked polymer networks, capable of providing localized and sustained delivery of a wide range of therapeutic agents, including cells. Among natural polymers, alginate has garnered significant attention as a hydrogel scaffold due to its excellent biocompatibility, low toxicity, and inherent biodegradability. Advances in the design and engineering of alginate hydrogels have enabled the development of next-generation drug and cell delivery systems that respond dynamically to various environmental stimuli. Beyond functioning as passive carriers, alginate hydrogels have evolved into interactive platforms that can engage in bidirectional communication with encapsulated or surrounding cells. These smart materials not only influence cellular behaviour but are also responsive to biochemical and biomechanical cues from the cellular microenvironment. This dynamic interplay, often described as "give-and-take" communication, relies on complex, integrated mechanisms. This review explores the latest advancements in alginate hydrogel fabrication, functionalization, and degradation, with particular emphasis on the mechanisms underpinning their interactive behaviour with cells and their potential in responsive, adaptive therapeutic systems.