Molecular-weight-dependent bioactivity of agarose for repairing UV-induced skin damage

Acute ultraviolet exposure disrupts the epidermal barrier, induces oxidative stress, and accelerates extracellular matrix degradation, necessitating effective strategies for photodamage repair. Here, we establish a molecular-weight-graded agarose system-Aga-U, Aga-H, Aga-M, and Aga-L-to assess the effect of molecular weight on the physicochemical and biological properties of agarose. Controlled hydrolysis generated agarose fractions with progressively reduced molecular weight, resulting in enhanced solubility, hydrophilicity, fluidity, and antioxidant capacity. All fractions exhibited good cytocompatibility and promoted zebrafish caudal-fin regeneration, with Aga-L demonstrating the strongest bioactivity. In vitro and in vivo evaluations, including fibroblast assays and zebrafish and UV-induced acute photodamage mouse models, revealed that Aga-L most effectively restored the epidermal barrier, reduced oxidative stress, and enhanced collagen deposition. Molecular analyses showed that Aga-L downregulated MMP-1, MMP-2, MMP-9, p-c-Fos, and p-c-Jun and upregulated Nrf2, HO-1, Col I and Col III. These findings identify low-molecular-weight agarose as a potent bioactive polysaccharide for repairing UV-induced skin injury and provide a basis for developing agarose-based therapeutic strategies.