New Strategies in Comprehensive Melanoma Treatment: Applications, Potential, and Challenges of Hydrogels.

With the rising incidence and mortality rates of melanoma, the limitations of traditional treatment methods have become increasingly evident. These approaches often lack precision, cause systemic toxicity, or fail to prevent recurrence, falling short of current treatment needs such as efficacy, safety, and long-term tumor control. Melanoma progression involves complex biological features such as uncontrolled proliferation, immune evasion, and metastasis, which are crucial for understanding clinical behavior and guiding treatment design. Hydrogels have recently emerged as a promising platform in the field of cancer therapy due to their tunable physicochemical properties, biocompatibility, and capacity for localized, controlled drug delivery. To provide a comprehensive and methodologically sound overview, we systematically searched the PubMed database using the keywords "hydrogel" and "melanoma" for studies published up to December 2024. Studies were screened based on relevance, originality, and experimental support. This review focuses on hydrogel-based strategies for melanoma treatment, highlighting: (1) recent advances in hydrogel design and functionality; (2) their integration with therapeutic approaches such as immunotherapy, chemotherapy, and photothermal therapy; and (3) their potential in postoperative wound management. In addition, we discuss the role of material selection in hydrogel performance and explore how the combination of distinct therapeutic approaches within hydrogel systems can synergistically improve treatment outcomes. Finally, we address the current challenges facing clinical translation, including safety, efficacy, and regulatory hurdles, while outlining potential pathways to overcome these barriers. This review aims to support future research and clinical innovation by providing a structured, up-to-date overview of hydrogel applications in melanoma therapy.