A Photothermally Active CuS-Nanocomposite Hydrogel for Postsurgical Melanoma Management and Tissue Regeneration

The postoperative management of melanoma remains challenging due to risks of local recurrence, bacterial infection, and delayed wound healing. To address these issues, we engineered an injectable and photoresponsive nanocomposite hydrogel by incorporating polyglutamic acid-grafted cysteine (PGAGS)-capped CuS nanoparticles into an EPL-GMA network. The hydrogel rapidly cross-links under 405 nm blue light within 25 s, forming a mechanically robust and degradable scaffold with excellent cytocompatibility. Upon 808 nm near-infrared irradiation, hydrogels with different E-CuS loadings exhibited rapid and loading-dependent temperature elevation, with E-CuS 3 and E-CuS 5 reaching 70.9 and 80.1 °C within 5 min, respectively, which is sufficient for the efficient thermal ablation of melanoma cells. Beyond direct hyperthermia-induced apoptosis, this photothermal effect triggers immunogenic cell death, as confirmed by the significant upregulation of CRT and HMGB1, leading to a 94.3%/95.1% reduction in tumor recurrence in vivo. Simultaneously, the sustained release of bioactive Cu²⁺ ions (∼1.55 μM) from the degrading hydrogel promotes angiogenesis, enhances collagen deposition, and accelerates the regeneration of resection-site tissue. This hydrogel also exhibits notable photothermal antibacterial efficacy, with approximately 99% elimination of Staphylococcus aureus and over 94% elimination of Escherichia coli. Its dual-functional design synergistically integrates photothermal tumor ablation with orchestrated tissue repair, offering a comprehensive therapeutic strategy with significant potential for postsurgical melanoma management and infected wound treatment.