Phase-specific and laser-modulated polydopamine-chlorella-curdlan hydrogels: pioneering a melanoma integrative therapy

Background: Patients with melanoma are confronted with postoperative challenges such as tumor relapse, impaired wound healing, infection, and hypertrophic scarring, with chronic wound inflammation potentially increasing the risk of tumor recurrence. Photoresponsive hydrogels have great potential for integrated postsurgical treatment of melanoma by embedding photosensitizers or photothermal agents in porous polymer networks, combining the advantages of hydrogels and phototherapy technologies. Methods: The photoresponsive PCCUR hydrogel was synthesized via a thermal induction method, incorporating polydopamine nanoparticles (PDA-NPs), Chlorella extract (CE), and curdlan (CUR). The physicochemical properties of PCCUR and its effects on skin cells and B16F10 cells were systematically evaluated through in vitro experiments. The antitumor recurrence efficacy of the PCCUR hydrogel was assessed via an incomplete melanoma resection model. Furthermore, the regulatory effects of PCCUR on infected wound healing and its inhibitory effects on hypertrophic scar formation were investigated under temporally controlled laser irradiation. Results: The photoresponsive PCCUR hydrogel possesses temperature sensitivity, injectable properties, optimal mechanical strength, and significant antimicrobial activity and is tailored to mitigate postsurgical issues through healing phase-specific laser irradiation adjustments. During the inflammatory phase, synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) not only eliminate infections but also induce immunogenic cell death (ICD), releasing tumor antigens that bypass tumor heterogeneity and are captured by the in situ hydrogel. The antigen-captured hydrogel acts as an “antigen reservoir” and releases captured antigens to recruit dendritic cells (DCs) to stimulate an antitumor immune response. In the proliferation phase, the inherent properties of the hydrogel inhibit inflammation and facilitate cell proliferation and angiogenesis. The remodeling phase involves low-intensity laser-based phototherapy to modulate myofibroblast activity and collagen remodeling, preventing hypertrophic scarring. Conclusions: The dynamic photoresponsive properties of PCCUR by introducing a 3R paradigm (Remove-Residual tumor cells/bacteria; Remodel-Immune microenvironment; Repair-Skin tissue) provide a safe and efficient therapeutic approach tailored to the three stages of wound healing, making it a promising dressing option for the comprehensive management of postoperative wounds in melanoma patients.