Engineering alginate hydrogels loaded with resveratrol as a dual platform for cancer therapy and wound regeneration

Abstract

Hydrogels represent a highly adaptable biomaterial platform for a broad range of biomedical uses, largely because they can replicate the extracellular matrix while retaining substantial amounts of aqueous fluid. Among the polymers employed for hydrogel fabrication, naturally derived macromolecules are particularly appealing thanks to their favorable biocompatibility and biodegradation profiles. Alginate, in particular, has drawn considerable attention as a matrix-forming polymer owing to its wide natural availability, low cost, and the relative ease with which it can be crosslinked into three-dimensional networks. Meanwhile, the therapeutic management of malignancies and non-healing wounds continues to impose considerable burdens on clinical and pharmaceutical practice. Resveratrol (RSV), a polyphenolic stilbene, has shown encouraging outcomes in addressing both conditions; nevertheless, its translation into the clinic is hampered by intrinsic drawbacks including limited solubility in aqueous media, marked hydrophobic character, and rapid elimination following administration. The present article surveys recent progress on RSV-loaded alginate hydrogel systems developed for oncological and wound-repair indications. Particular attention is devoted to the molecular mechanisms underlying RSV action and to its intracellular disposition. Subsequently, the review details the principal fabrication strategies used to incorporate RSV within alginate networks, together with the structural and environmental variables that modulate drug release. The discussion closes by highlighting avenues for improving therapeutic performance and outlining forward-looking strategies for engineering next-generation RSV-alginate hydrogel platforms with broadened application scope. Distinct from previous reviews, this work is organized around the structure–function relationships that govern RSV bioavailability within alginate matrices, and it treats the two therapeutic fronts—oncology and wound repair—where alginate-based delivery offers the greatest translational leverage in an integrated framework. The manuscript is intended for formulation scientists, biomaterials engineers, and translational researchers seeking practical design guidelines rather than a catalogue of individual studies. Specifically, readers will find (i) comparative analysis of encapsulation strategies with their quantitative performance metrics, (ii) explicit linkage between hydrogel network parameters (crosslinking density, mesh size, porosity) and in vivo therapeutic outcomes, and (iii) a critical assessment of the barriers—scalability, regulatory harmonization, long-term safety, and batch reproducibility—that currently separate bench-scale performance from clinical translation.