The Future of Bladder Cancer Therapies: Integrating Hydrogel Scaffolds for Epigenetic Regulator Delivery.

Urine rapidly dilutes and eliminates intravesical chemotherapies, making non-muscle-invasive bladder cancer (NMIBC) a clinical challenge. Reverse thermal hydrogels, mucoadhesive polymers, and tissue-engineered scaffolds have been developed to improve dwell time and target drug delivery. Recent Food and Drug Administration-approved hydrogel formulations have achieved high complete response rates in low-grade intermediate-risk NMIBC. At the same time, dysregulated epigenetic regulators such as lysine demethylase 6A and enhancer of zeste homolog 2, as well as methylation signatures detectable in urine, are revealing new therapeutic and diagnostic avenues. This narrative review synthesizes evidence on hydrogel-based delivery and scaffolding, arguing that combining sustained-release platforms with local epigenetic therapy and regenerative scaffolds represents the next frontier in NMIBC treatment, potentially reducing recurrence while improving bladder preservation.