A Systematic Review of Aptamer‐Based Alginate‐Agarose Hydrogel Strategies for Inhibiting Keloid Fibrosis and Hypertrophic Scarring

ABSTRACT Background Abnormal wound healing leading to keloids and hypertrophic scars is driven by persistent fibroblast activation and excessive extracellular matrix accumulation, yet effective therapeutic options remain limited. Novel approaches, including nucleic acid aptamers and biomaterial‐based delivery platforms, have recently attracted attention. Objective This study systematically reviews current research on the application of DNA aptamers and alginate–agarose hydrogels in fibrosis‐related conditions. Methods Literature searches were performed in PubMed, Web of Science, and Scopus for studies published between January 2000 and March 2025. Studies meeting predefined criteria were grouped according to their primary focus on aptamer‐based targeting, hydrogel‐based delivery, or combined strategies. Due to heterogeneity, the included studies were synthesized descriptively. Results Sixteen studies were included. Investigations of aptamers primarily addressed modulation of profibrotic signaling pathways, particularly those associated with TGF‐β and IL‐6. Hydrogel systems, especially alginate and agarose formulations, were mainly explored for their ability to prolong local drug retention and enable controlled release. Integrated approaches combining both strategies were rarely reported. Conclusion Both aptamer‐based targeting and hydrogel‐mediated delivery demonstrate potential in fibrosis management. However, the predominance of preclinical evidence and the limited development of integrated systems indicate that further research is required to advance clinical translation.